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Medicinal & Pharmaceutical Chemistry glossary &
taxonomy
Evolving Terminology for Emerging Technologies Comments? Questions?
Revisions? Mary Chitty MSLS mchitty@healthtech.com
Last revised
January 09, 2020
Chemistry comes
into play in the form of chemical probes or as compounds being evaluated as
potential leads or drugs. The use of chemical probes to elucidate biology is
the basis of chemical genomics. A large series of compounds are individually
introduced into cells, with the aim of identifying a cell that then undergoes
a specific phenotypic change. By identifying the compound introduced into that
cell, and then finding which gene or protein was bound by the chemical probe,
the researcher succeeds in finding both a genetic link to a change in
phenotype and a chemical probe that can cause that change to occur.
Related
glossaries include Assays & screening
Bioprocessing Combinatorial
libraries & synthesis
Drug
discovery & development Drug targets
Metabolic
engineering Pharmacogenomics Informatics: Cheminformatics
Drug discovery informatics
Technologies: Labels,
signaling & detection
Mass
spectrometry Microarrays
Miniaturization
& nanoscience Biology: Expression gene & protein
Nomenclature Pharmaceutical biology
aliquot
in analytical chemistry: A known
amount of a homogeneous material, assumed to be taken with negligible sampling
error. The term is usually applied to
fluids. The term 'aliquot' is usually used when the fractional part is an
exact divisor of the whole; the term 'aliquant' has been used when the
fractional part is not an exact divisor of the whole (e.g. a 15 ml portion
is an aliquant of 100ml). When a laboratory
sample or test
sample is 'aliquoted' or otherwise
subdivided, the portions have been called split samples. IUPAC Gold Book
https://goldbook.iupac.org/html/A/A00218.html
Analytical Support for Drug
Product Development
May 4-8, 2020 Boston, MA
Overcoming the Analytical and Formulation
Challenges of a New Generation of Drug Products
Advances in protein
science, drug combinations, delivery technology and analytical methods are
supporting an unprecedented wave in novelty in the design of biologic drug
products. With these new products comes the urgent need for analytical
support of product development, regulatory filings and manufacturing – in
ways that require a constant adaptation by analytical and formulation
groups to new modalities and technologies.
https://www.pegsummit.com/Analytical-Support-for-Drug-Development
API
active pharmaceutical ingredients
The dosage
form for a pharmaceutical contains
the active pharmaceutical ingredient (API), which is the drug itself, and excipients,
which are the substances of the tablet, or the liquid the API is suspended
in, or other material that is pharmaceutically inert.
Drugs are chosen primarily for their active ingredients. Wikipedia
accessed 2018 Dec 2
https://en.wikipedia.org/wiki/Active_ingredient#Pharmaceuticals
biochemical genomics:
We have recently developed a biochemical
genomics approach to identify genes by the activities of their products,
together with Stan Fields (Univ. Washington) and E. Grayhack. To this end,
we first constructed a library of ca. 6000 strains, each of which expresses
a unique yeast ORF as a GST- ORF fusion. To identify genes encoding different
activities, the GST- ORFs are purified in pools, activity is assayed, and
active pools are deconvoluted to determine the GST- ORF responsible for
activity. Using this approach we have linked three previously unknown gene
products with specific biochemical activities. MR Martzen et al University of Rochester, US
“A
biochemical genomics approach for identifying genes by the activity of
their products. Science 286: 1153-155, 1999 http://www.sciencemag.org/content/286/5442/1153.abstract
Related terms: chemical genomics,
chemogenomics
biologically
relevant chemical space: Those parts of
chemical space in which biologically active compounds reside. Christopher M.
Dobson, "Chemical
space and biology" Nature 432 (7019): 824- 828, Dec. 16, 2004 Broader term:
chemical space
bioorganic
chemistry:
publishes research that addresses biological questions at the molecular level,
using organic chemistry and principles of physical organic chemistry. The scope
of the journal covers a range of topics at the organic chemistry-biology
interface, including: enzyme catalysis, biotransformation and enzyme inhibition;
nucleic acids chemistry; natural product chemistry and natural product
biosynthesis; antimicrobial agents; lipid and peptide chemistry; biophysical
chemistry; and biomimetic chemistry.
BioOrganic Chemistry, Elsevier Scope note
https://www.journals.elsevier.com/bioorganic-chemistry
Biophysical Approaches for Drug Discovery
New Methods and Lead Generation Strategies for Medicinal Chemists
APRIL 12, 2019 San Diego CA
Recent advances in automation and sensitivity of
biophysical approaches for measuring biomolecules interacting with one
another has spurred progress in drug discovery. Technologies such as
nuclear magnetic resonance (NMR), surface plasmon resonance (SPR), other
biosensor-based assays, isothermal titration calorimetry (ITC), and
thermal shift assays (TSAs) have enabled discovery of compounds targeting
protein-protein interactions and complex membrane protein targets. These
target classes are more difficult to ‘drug’ because they are either harder
to solubilize or not as amenable as are traditional intracellular enzyme
targets to in-vitro-based, biochemical functional assays for high
throughput screening. Fragment-based drug design is also another lead
generation approach that is very dependent on biophysical technologies. https://www.drugdiscoverychemistry.com/Biophysical-Approaches/
biophysical
characterization: Technologies for include circular dichroism and Fourier-transform infrared
spectroscopy
Biotherapeutics Analytical Summit
June 1-5, 2020 • Alexandria VA | https://www.biotherapeuticsanalyticalsummit.com/
brings together analytical scientists from biotherapeutics discovery,
analytical development, pharmaceutical sciences, process development,
formulation, technical development to discuss experiences and share best
practices on selecting, developing and characterizing new & emerging
molecules and bringing them faster to clinic, and to market.
biotransformation:
The chemical conversion of substances by living
organisms or enzyme preparations. IUPAC Medicinal Chemistry
The chemical alteration of an exogenous substance by or in a biological
system. The alteration may inactivate the compound or it may result in the
production of an active metabolite of an inactive parent compound. The
alteration may be either non- synthetic (OXIDATION- REDUCTION; HYDROLYSIS)
or synthetic (glucuronide formation, sulfate conjugation, ACETYLATION;
METHYLATION). This also includes metabolic detoxication and clearance.
MeSH, 1970
characterization: Can include
determining identity, physical chemistry data, purity, potency, quality,
stability, strength, pharmacokinetics, dose response, and
efficacy.
I am still trying to understand all the nuances of "characterize" and
"characterization" of
genes,
genomes,
proteins and
proteomes and how these
relate to annotation and would welcome any insights from people working in these
areas.
Related
terms: specified biotechnology product, well characterized; characterization, protein
Proteins;
Bioinformatics annotation Narrower
term: biophysical characterization
Characterization of Biotherapeutics
January 20-21, 2020 San Diego, CA
|
leading
scientists from biopharmaceutical industry, academia and government will
discuss case studies, new technologies, assays on analytical development
and characterization of mAbs, ADCs, bispecifics, and other novel protein
formats, biosimilar. Some of the hot topics for discussion this year will
include discuss regulatory expectations and developability of new product
formats, cell and gene therapy products, biosimilars, high-throughput
analytics, multi-attribute methods, glycosylation/post-translational
modifications and biophysical assays https://www.chi-peptalk.com/characterization-of-biotherapeutics
Characterization
of Biotherapeutics
Exploring the Analytical Challenges of Today’s Complex
Biologics
May 4-5 2020
Boston MA As new product formats progress through development and into the
regulatory process, the role of analytical characterization is taking on
new meaning. Very new modalities present challenges to both analytical
scientists and regulatory agencies alike, and this steep learning curve
requires a near-constant cycle of adaptation and innovation. The agencies
are requiring sponsors to provide ever more complex data across a wide
range of analytical methods, and instrumentation suppliers are striving to
support this new era with unique product features, software and feature
combinations.
https://www.pegsummit.com/Biotherapeutics-Characterization/ chemical biology:
ACS Chemical Biology provides an
international forum for the rapid communication of research that broadly
embraces the interface between chemistry and biology. The journal also serves
as a forum to facilitate the communication between biologists and chemists
that will translate into new research opportunities and discoveries. Results
will be published in which molecular reasoning has been used to probe
questions through in vitro investigations, cell biological methods, or
organismic studies. We welcome mechanistic studies on proteins, nucleic acids,
sugars, lipids, and nonbiological polymers. The journal serves a large
scientific community, exploring cellular function from both chemical and
biological perspectives. American Chemical Society, About the Journal
Chemical Biology http://pubs.acs.org/page/acbcct/about.html
Related term: chemical genomics
chemical genetics:
"Chemical genetics
approach" first coined [by Rebecca Ward, at Harvard University] on the
inaugural cover of Chemistry and Biology nine years ago. Her term reminds us
that to understand a life process you should perturb it and determine the
consequence and that such an approach should strive to have the broad power and
generality of genetics. Stuart L. Schreiber, The Small Molecule Approach
to Biology, Chemical & Engineering News, March 3, 2003 http://www-schreiber.chem.harvard.edu/home/pdffiles/8109genomics.pdf
Related terms: chemical genomics, chemogenomics
chemical genomics:
The targets of many drug candidates are unknown and are often difficult to
tease out from among the thousands of gene products found in a typical
organism. The “blindness” in the welter of potential cellular targets
means that the process of designing therapeutic drugs is neither precise nor
efficient. The exploration of chemical genomics will transform our
understanding of how the human genome and proteome function. Related/near synonymous? terms: chemical
genetics, chemical genomics
chemical mutagenesis:
Systematic mutagenesis using chemical with
mutagenic properties.
chemical proteomics: The
medical and pharmaceutical communities are facing a dire need for new druggable
targets, while, paradoxically, the targets of some drugs that are in clinical
use or development remain elusive. Many compounds have been found to be more
promiscuous than originally anticipated, which can potentially lead to side
effects, but which may also open up additional medical uses. As we move toward
systems biology and personalized medicine, comprehensively determining small
molecule-target interaction profiles and mapping these on signaling and
metabolic pathways will become increasingly necessary. Chemical proteomics is a
powerful mass spectrometry-based affinity chromatography approach for
identifying proteome-wide small molecule-protein interactions.
Nat
Chem Biol. 2009
Sep;5(9):616-24. doi: 10.1038/nchembio.216. Target profiling of small molecules by chemical
proteomics.
Rix
U, Superti-Furga
G.
http://www.ncbi.nlm.nih.gov/pubmed/19690537
Makes use of synthetic small molecules that can be
used to covalently modify a set of related enzymes and subsequently allow their
purification and/or identification as valid drug targets. Furthermore, such
methods enable rapid biochemical analysis and small- molecule screening of
targets thereby accelerating the often difficult process of target validation
and drug discovery. DA Jeffery, M. Bogyo, Chemical
proteomics and its application to drug discovery, Current Opinion in
Biotechnology 14(1): 87-95, Feb. 2003
Related
term/equivalent?: chemiproteomics
chemical
space: The heartland of this debate [about how many samples
are enough] centres on the definition, and hence extent, of chemical space.
More precisely, it focusses on the extent of chemical space that is
accessible by chemical synthesis and which could be described as drug- like.
[Martin J. Valler, Darren Green "Diversity
screening versus focussed screening in drug discovery " Drug
Discovery Today 5(7): July 2000
Encompasses all
possible small organic molecules, including those present in biological
systems--is vast. So vast, in fact, that so far only a tiny fraction of it has
been explored. ... A term often used in place of 'multi- dimensional descriptor
space'; it is a region defined by a particular choice of descriptors and the
limits placed on them. In the context of this insight, chemical space is defined
as the total descriptor space that encompasses all the small carbon -
based molecules that could in principle be created. Christopher M. Dobson, "Chemical
space and biology" Nature 432 (7019): 824- 828, Dec. 16, 2004 Narrower term:
biologically relevant chemical space.
Related term: property
space
chemical tools:
small molecules used as probes of a chemical or biological process.
Studying the effects of chemical tools on a system can lead to new insight
into the molecular target of the small molecule and the pathways it acts
in. Chemical probes with defined targets can be attractive as drugs in
clinical pharmacology. http://www.nature.com/subjects/chemical-tools
Related term: tool compounds
chemiexcitation, chemiluminescence: Labels,
signaling & detection
chemogenomics:
There is some confusion about the meaning of the term
'chemogenomics'103;
this might be expected given the involvement of so many disciplines. In
particular, there is considerable overlap among the related strategies
described by the terms 'chemical genetics'104
and 'chemical genomics'105,
106.
Although these three terms are sometimes used interchangeably, the primary
goal of both of the last two strategies is the study of cellular function
using small synthetic molecules as modulating ligands. By contrast, the
term 'chemogenomics' is often used to describe the focused exploration of
target gene families, in which small molecule leads — identified by
virtue of their interaction with a single member of a gene family — are used
to study the biological role of other members of that family, the function of
which is unknown. Box 1 Defining chemogenomics
from the following article: Chemogenomics: an emerging strategy for rapid
target and drug discovery, Markus Bredel & Edgar Jacoby, Nature Reviews
Genetics 5, 262-275 April 2004 https://www.nature.com/articles/nrg1317#B105
Sometimes referred to as chemical genomics.
was most likely first used
by Vertex Pharmaceuticals to describe its parallel drug design approach,
which involves using structures of proteins in a given family to design
drugs for the family as a whole. The Vertex approach is truly parallel
(i.e., involving multiple targets at once) and combines structural biology,
biased library design and screening, and structure- based drug
design. At
its limit, chemogenomics represents the discovery and description of all
possible compounds that can interact with any protein encoded by the human
genome. The term chemogenomics is slowly (and somewhat grudgingly) catching
on. Broadly, it now appears to mean “taking a combinatorial approach
to screening protein targets by family/ class.” Detailed protein structure
information is used to design libraries that are “biased” to contain compounds
that are more likely to interact with a particular protein family (hence,
it is a “genomic” approach). This screening methodology helps researchers
identify the best small molecule compound to bind to a target (hence it
is a “chemical” approach).
;;;
chemogenomics
or chemical
genomics, is the systematic screening of
targeted chemical
libraries of small
molecules against
individual drug
target families
(e.g., GPCRs, nuclear
receptors, kinases, proteases,
etc.) with the ultimate goal of identification of novel drugs and
drug targets.[1] Typically
some members of a target library have been well characterized where both the
function has been determined and compounds that modulate the function of those
targets (ligands in
the case of receptors, inhibitors of enzymes,
or blockers of ion
channels) have
been identified. Other members of the target family may have unknown function
with no known ligands and hence are classified as orphan
receptors. By
identifying screening hits that modulate the activity of the less well
characterized members of the target family, the function of these novel targets
can be elucidated. Furthermore, the hits for
these targets can be used as a starting point for drug
discovery. The
completion of the human genome project has provided an abundance of potential
targets for therapeutic intervention. Chemogenomics strives to study the
intersection of all possible drugs on all of these potential targets.[2]
Wikipedia
accessed 2018 Aug 22
https://en.wikipedia.org/wiki/Chemogenomics
Related, (near) synonymous terms: chemical genomics, chemical genetics Narrower terms:
functional chemogenomics, structural chemogenomics; In
silico & Molecular
modeling in silico chemical genomics
chemistry & drug discovery:
Much of the impact of genomics on drug
development thus far has been focused on the identification and validation of
biological targets. While much of this research on targets is based only on
comparisons of the biology of health and disease, sooner or later it becomes
critical to integrate the activity of chemical compounds with the body. CHI’s
Drug Discovery and Development Map
Chemistry Manufacturing & Controls CMC:
To appropriately manufacture a
pharmaceutical or biologic specific manufacturing processes, product
characteristics, and product testing must be defined in order to ensure
that the product is safe, effective and consistent between batches. These
activities are known as CMC, chemistry, manufacturing and control. All
stages of the drug development life cycle, after drug discovery involve
CMC. During preclinical drug development, the proper analytical methods
are validated to monitor the product. Stability testing may be initiated,
the physicochemical properties of the product are determined, raw
materials are chosen and tested. When the drug development process moves
into the clinical stage, further analytical method validation is required,
and additional characterization of the drug product is needed. After
clinical trials the scale up process must ensure that the larger batches
of product are the same and meet the same specifications as the drug
tested in the clinical trials. After the manufacturing process is
qualified, lot release and in process testing will continue to take place.
Pacific BioLabs
https://pacificbiolabs.com/cmc-chemistry-manufacturing-and-controls
FDA
Pharmaceutical Quality CMC guidelines
https://www.fda.gov/animal-veterinary/guidance-industry/chemistry-manufacturing-and-controls-cmc-guidances-industry-gfis
See also
Bioprocessing, Drug
Discovery & Development
chemoproteomics:
The use of biological information to guide chemistry--offers a highly
efficient alternative to small-molecule characterization that can
accelerate drug discovery. Beroza P, Villar HO, Wick MM, Martin GR.
Chemoproteomics as a basis for post-genomic drug
discovery, Drug Discov Today, 7(15):
807- 814, Aug 1, 2002 Related
terms: chemical proteomics, chemiproteomics
chiral:
Having the property of chirality. As applied to a molecule
the term has been used differently by different workers. Some apply it
exclusively to the whole molecule, whereas others apply it to parts of
a molecule. IUPAC Compendium
chirality:
The geometric property
of a rigid object (or spatial arrangement of points or atoms) of being
non- superimposable on its mirror image; such an object has no symmetry
elements of the second kind. IUPAC Compendium Related terms: enantiomer,
handedness.
chromophore:
That part of a molecular entity consisting of an
atom or group of atoms in which the electronic transition responsible for
a given spectral band is approximately located. IUPAC Bioinorganic IUPAC
Photochem
compound: A chemical compound is
a chemical
substance composed of many identical molecules (or molecular
entities) composed of atoms from
more than one element held
together by chemical
bonds. A chemical
element bonded to an identical
chemical element is not a chemical compound since only one element, not
two different elements, is involved. There are four types of compounds,
depending on how the constituent atoms are held together:
molecules held
together by covalent
bonds,
ionic compounds held
together by ionic
bonds,
intermetallic compounds held
together by metallic
bonds, certain complexes held
together by coordinate
covalent bonds. Wikipedia accessed
2018 Dec 2
https://en.wikipedia.org/wiki/Chemical_compound
compound
quality:
Physicochemical properties such as lipophilicity and molecular mass are
known to have an important influence on the absorption, distribution, metabolism,
excretion and toxicity (ADMET) profile of small-molecule drug candidates. To
assess the use of this knowledge in reducing the likelihood of compound
related attrition, the molecular properties of compounds acting at specific
drug targets described in patents from leading pharmaceutical companies during
the 2000-2010 period were analysed. ... we conclude that a substantial
sector of the pharmaceutical industry has not modified its drug design
practices and is still producing compounds with suboptimal physicochemical
profiles. Paul D. Leeson and Stephen A St-Gallay The influence of the
"organizational factor" on compound quality in drug discovery,
Nature Reviews Drug Discovery, 10:749-765, October 2011 http://www.ncbi.nlm.nih.gov/pubmed/21959288 Figures and tables http://www.nature.com/nrd/journal/v10/n10/fig_tab/nrd3552_ft.html
compound
profiling: Biology has
considerable experience with gene and protein- centered informatics, but
chemistry is at an earlier stage of developing databases that are truly
compound- centric. The historical paradigm of identifying and optimizing
hits for potency, and then looking to evaluate and optimize for ADME and
toxicity properties is quickly shifting to a more parallel approach that
considers ADME/Tox properties at an earlier stage. This concept is
epitomized by methods for differentiating between drug- like and non-
drug- like compounds, the use of which is increasing significantly. Moving
compound profiling earlier means that many more compounds must be
assessed, which is both the value and the challenge of this shift.
compound validation:
Assays & screening
congener:
A substance literally con- (with) generated or
synthesized by essentially the same synthetic chemical reactions and the same
procedures. Analogs are substances that are analogous
in some respect to the prototype agent in chemical structure.
Clearly congeners may be analogs or vice versa but not
necessarily. The term congener, while most often a synonym for homologue,
has become somewhat more diffuse in meaning so that the terms congener
and analog are frequently used interchangeably in the literature. IUPAC
Medicinal Chemistry
Dalton:
Unit of mass equal to the unified atomic mass (atomic
mass constant).[IUPAC Compendium After John Dalton (1766-1844)
British chemist and physicist.
Frequently used in biochemistry to express
molecular mass, although the name and the symbol [Da] have not been approved by
CIPM [Comité international des poids et mesures] or ISO [International
Organization for Standardization]. IUPAC Quantities
dimer:
A molecule which consists of two similar (but not necessarily identical) subunits. The term could also be used as a verb referring to the
act of
the two subunits coming together (to dimerize). 09 Oct 1997 OMD
Directed Evolution-Based Drug Discovery
DNA Encoded Libraries and Other Diversity Oriented Platforms APRIL 9-10,
2019 San Diego CA Directed evolution approaches for drug discovery use
genetic strategies (DNA-encoded, RNA-encoded or phage-based) to create
very large but specific libraries of molecules whose amplification is
driven by the target of interest. The theory was established decades ago
but recently applications in early stage drug discovery have become more
widespread. A few drug candidates arising from directed evolution
campaigns are now in clinical trials. A bottleneck however of these
diversity-oriented strategies is figuring out which hits to focus on from
the many hits that are produced by these approaches.
https://www.drugdiscoverychemistry.com/Directed-Evolution
Drug
Discovery Chemistry April
13-17, 2020 • San Diego, CA Program |
Optimizing
Small Molecules for Tomorrow's Therapeutics Focused on discovery and
optimization challenges of small molecule drug candidates, including coverage
of Artificial Intelligence for Early Drug Discovery
https://www.drugdiscoverychemistry.com/
enantiomer: One of a pair of molecular entities that are mirror
images of each other and non- superimposable. IUPAC Bioinorganic Also called optical isomers. Related terms:
chirality, racemate.
fine
chemicals: Pure, single substances that are produced by chemical reactions
and are bought and sold on the basis of their chemical identity. Pharmaceutical
fine chemicals include both intermediates for drug production and bulk active
drugs ready to be compounded with inert pigments, solvents, and fillers --
called excipients -- and made into dosage forms. The combination of fine
chemicals and performance chemicals makes up the group called specialty
chemicals. As opposed to fine chemicals, performance chemicals are
often mixtures of substances, proprietary products, formulated with carriers or
solvents, and bought and sold for what they do. What are fine chemicals? Pharmaceutical
Fine Chemicals, Chemical & Engineering News, July 10, 2000
http://pubs.acs.org/cen/coverstory/7828/7828spec.html#Anchor-1344
flow
chemistry:
In flow chemistry a
chemical
reaction is run in a continuously flowing
stream rather than in batch production.
In other words, pumps move fluid into a tube, and where tubes join one
another, the fluids contact one another. If these fluids are reactive, a
reaction takes place. Flow chemistry is a well-established technique for use
at a large scale when manufacturing large
quantities of a given material. However, the term has only been coined
recently for its application on a laboratory scale. Often, microreactors are
used.
Wikipedia accessed Oct 11 2017 http://en.wikipedia.org/wiki/Flow_chemistry
forward [chemical] genetics:
Phenotypic
screening of chemical
libraries is used to identify drug targets (forward
genetics) or to validate
those targets in experimental models of disease (reverse
genetics).[2
Wikipedia Chemical Genetics accessed 2018 July 23
https://en.wikipedia.org/wiki/Chemical_genetics
Fragment-Based Drug Discovery From Hits to Leads
and Lessons Learned APRIL 14-15. 2020
Fragment-based drug discovery (FBDD) has proven to be a successful
approach for finding new drug compounds, especially against difficult
targets such as intracellular protein-protein interactions (PPIs). Quite a
few drugs on the market today can trace their origins to hits from
fragment-based library screening campaigns. Now that FBDD has been folded
into many early drug discovery departments, questions such as how to merge
hits arising from fragment-based screens with hits from traditional high
throughput screening methods are more frequent. Plus, the challenge of
growing fragment hits into drug leads still remains, especially when the
fragment and target do not have co-crystal structures to guide ligand
design
https://www.drugdiscoverychemistry.com/Fragment-Based-Drug-Discovery/
genochemistry
genomic chemistry:
The volume of data from biological and chemical
studies has been increasing exponentially in recent years. In particular,
there are now 150 billion sequences within GenBank, 60k protein structures
in PDB, and 50 million chemicals with unique structures (as of Sept.
7, 2009, CAS). As a result, one of the most important challenges has
been the annotation of genetic sequences to their functions, and enzymes
(encoded by their sequences) to their substrate profiles. A
systematic study of chemistry that links the enzyme's sequence information
(including SNP) and substrate structural diversity is needed. It
differs from traditional disciplines in many ways and requires a
restructuring of established methods, the standardization of the data
collection process, and new bioinformatics and modeling tools. It can take
the form of extended biocatalysis complemented by bioinformatics and
molecular modeling. We tentatively refer to this discipline as
Genochemistry.
IUPAC, Genochemistry -- chemistry
designed for life sciences: Towards a guideline and a framework of
genochemistry, 2010 IUPAC
Project Number 2009-021-3-300. A
glossary of specialized terms will be included.
https://iupac.org/projects/project-details/?project_nr=2009-021-3-300
green
chemistry: The terminology "green chemistry"
or "sustainable chemistry" is the subject of debate. The expressions
are intended to convey the same or very similar meanings, but each has its
supporters and detractors, since "green" is vividly evocative but may
assume an unintended political connotation, whereas "sustainable" can
be paraphrased as "chemistry for a sustainable environment", and may
be perceived as a less focused and less incisive description of the discipline.
Other terms have been proposed, such as "chemistry for the
environment" but this juxtaposition of keywords already embraces many
diversified fields involving the environment, and does not capture the economic
and social implications of sustainability. The Working Party decided to adopt
the term green chemistry for the purpose of this overview. This decision does
not imply official IUPAC endorsement for the choice. In fact, the IUPAC
Committee on Chemistry and Industry (COCI) favors, and will continue to use
sustainable chemistry to describe the discipline. Special Topic Issue on Green
Chemistry, Pure Appl. Chem., Vol. 72, No. 7, pp. 1207-1228, 2000 http://www.iupac.org/publications/pac/2000/7207/7207tundo.html
handedness:
Chirality
and handedness are concepts that apply to the structure of molecules. Chirality
is defined by the lack of certain features of symmetry, which lead to an object
not being superimposable on its mirror image. Handedness is a different
phenomenon relating to the ability to classify chiral objects into right-handed
and left-handed objects. All handed objects are chiral, but not all chiral
objects are handed. In 1968 through 1970, Ruch and coworkers developed a theory
of chirality that provided a mathematical basis for the handedness of chiral
objects. Handed chiral objects are considered to be analogous to shoes, which
are readily classified into right and left shoes regardless of the size,
material, style, or other attributes of the shoes in question. Nonhanded chiral
objects are considered to be analogous to potatoes, which have no symmetry
because of their irregular patterns of "bumps" and "eyes,"
thereby meeting the lack of symmetry requirements for chirality. There is,
however, no unambiguous way to classify a set of potatoes into "left"
and "right" potatoes. RB King, Chirality
and handedness: the Ruch "shoe-potato" dichotomy in the right- left
classification problem, Annals of the New York Academy of Sciences
988: 158- 170, May 2003 Related term: chirality
hard drug:
A
nonmetabolizable compound, characterized either by high lipid solubility and
accumulation in adipose tissues and organelles, or by high water
solubility. In the lay press the term "hard Drug"
refers to a powerful drug of abuse such as cocaine or heroin. IUPAC
Medicinal Chemistry heterodimer:
biochemistry A dimer in which the two subunits are different.
hydrophilicity:
The tendency of a molecule to be solvated by water. IUPAC Medicinal
Chemistry
hydrophilization:
The process of modifying proteins or polymers to make them more stable. A
number of methods can be used.
hydrophobicity
is the association of non-polar groups or molecules in an aqueous environment
which arises from the tendency of water to exclude non polar molecules. (See
also Lipophilicity).
IUPAC Medicinal Chem
immunochemistry:
Study of biochemical and molecular aspects of immunology, especially the nature
of antibodies, antigens and their interactions. IUPAC Gold Book
https://goldbook.iupac.org/html/I/I02980.html
The field of immunochemistry is becoming increasingly important in different
disease states with respect to the development of diagnostics and
therapeutics. The objective is to compile present knowledge of the molecular
basis of immunochemical interactions, to summarize the rapidly expanding
applications in many health-related areas, and to critically discuss the
upcoming research needs. Completed 2014
https://iupac.org/projects/project-details/?project_nr=2010-051-1-700
isomer: Molecules with identical molecular
formulas but different structural
formulas. Fred Senese, General Chemistry
Glossary, Frostburg State University, 2001] http://antoine.frostburg.edu/chem/senese/101/glossary.shtml
lipophilicity:
represents the affinity of a molecule or a moiety
for a
lipophilic
environment. It is commonly measured by its distribution behaviour in a
biphasic system, either liquid-liquid (e.g.,
partition coefficient
in 1-octanol/water) or solid-liquid (retention on reversed-phase
high-performance liquid chromatography
(RP-HPLC) or
thin-layer chromatography
(TLC) system). IUPAC Gold Book
https://goldbook.iupac.org/terms/view/LT06965
kDA:
Kilo Dalton
Kinase Inhibitor Chemistry April
14-15, 2020 • San Diego, CA | Kinase
inhibitor discovery is a very active area as developers are exploring more
deeply into designing immune-modulatory agents as single or combination
therapies, tackling chronic disease indications, such as inflammation and CNS
disorders, as well as effectively harnessing allosteric modulators, and
covalently binding compounds. will also be discussing the role of artificial
intelligence, new and non-oncology drug targets, phosphatases, and protein
degraders in kinase development.
https://www.drugdiscoverychemistry.com/Kinase-Inhibitor-Chemistry/
Macrocyclics and Constrained Peptides April
14-15, 2020 • San Diego, CA | In
the drug discovery industry, synthetic macrocyclic compounds theoretically fit
the bill for new chemical entities that have good drug potential yet can
access newer drug targets such as protein-protein interactions (PPIs) that are
intracellular and more complex than traditional enzymatic targets. Indeed,
there are examples of naturally occurring macrocyclics, such as cyclosporin,
that have become successful drug compounds. Synthetic macrocyclics'
'idealness,' however, is still being optimized.
https://www.drugdiscoverychemistry.com/macrocyclics/
materials
chemistry:
comprises the application of chemistry to the design, synthesis,
characterization, processing, understanding, and utilization of materials,
particularly those with useful, or potentially useful, physical properties.
https://iupac.org/materialschemistryedu/
We propose the following working definition, based on a synthesis
of the above suggestions and the currently accepted meaning of materials
in most dictionaries and books:
Materials chemistry comprises the
application of chemistry to the design, synthesis, characterization,
processing, understanding, and utilization of materials, particularly
those with useful, or potentially useful, physical properties.
This definition draws upon the existing definitions for the terms
“chemistry” and “materials,” while acknowledging that the materials that
have been (and are likely to continue to be) of particular interest to the
practitioners are generally those that have certain properties—e.g.,
mechanical, electrical, magnetic, optical, etc.—that make them useful, or
potentially useful, in a functional sense. Thus, the keywords “useful” and
“properties” were added to further define the materials that are most
likely to be the subject of investigation in this field as well as to
acknowledge the fact that functionality, or the prospect of functionality,
is a major driver for research and development in the field.
IUPAC What
Is "Materials Chemistry"?
Vol. 31 No. 3 May-June 2009
Peter Day, Leonard Interrante, and Anthony
West
https://old.iupac.org/publications/ci/2009/3103/1_day.html
medicinal chemistry:
A chemistry
based discipline, also involving aspects of biological, medical and pharmaceutical
sciences. It is concerned with the invention, discovery, design, identification
and preparation of biologically active compounds, the study of their metabolism,
the interpretation of their mode of action at the molecular level and the
construction of structure- activity relationships IUPAC Medicinal
Chemistry
It has been 10 years
since the first [IUPAC] Glossary of Terms Used in Medicinal Chemistry
was published. During this period, a remarkable change in medicinal chemistry
practice has occurred, largely in response to the genomic revolution,
including the introduction of combinatorial chemistry, robotic techniques, and
parallel synthesis. It has brought with it an accompanying vocabulary of new
terminology. There is a particular need to address the terminology associated
with chemogenomics, chemoinformatics, newer strategies for hit and lead
discovery, and those parameters that deal specifically with chemical diversity
and drug-likeness. Chemistry International Mar-Apr 2009 http://www.iupac.org/publications/ci/2009/3102/pp2_2008-010-1-700.html
Wikipedia http://en.wikipedia.org/wiki/Medicinal_chemistry
-mer:
This suffix is often used to indicate the number of nucleotides
in an oligonucleotide, e.g. 30-mer, 19-mer. [ICN] Related terms dimer,
monomer, trimer, up to 10 nucleotides decamer. Eleven and above are the
number plus -mer.
millamolecules:
mid-range compounds that fall in size between small molecules and
biologics. Size is not the only consideration for this class, as
millamolecules should also be orally available and able to interrupt
protein-protein interactions. Bristol Myers Squibb: Areas of Focus
https://www.bms.com/researchers-and-partners/areas-of-focus.html
molality:
The molal unit is not used nearly as frequently as the molar
unit. A molality is the number of moles of solute dissolved in one kilogram
of solvent. Be careful not to confuse molality and molarity. Molality is
represented by a small "m," whereas molarity is represented by an
upper case "M." [Roberta Crowell Barbalace "Molarity,
Molality and Normality" 2006 http://environmentalchemistry.com/yogi/chemistry/MolarityMolalityNormality.html
molarity:
The molar unit is probably the most commonly used chemical
unit of measurement. Molarity is the number of moles of a solute dissolved in
a liter of solvent. [Roberta Crowell Barbalace "Molarity, Molality and
Normality" 2006 http://environmentalchemistry.com/yogi/chemistry/MolarityMolalityNormality.html
molecular
scaffold:
The molecular scaffold is an
oft-cited concept in medicinal chemistry suggesting that the definition of what
makes a scaffold is rigorous and objective. However, this is far from the case
with the definition of a scaffold being highly dependent on the particular
viewpoint of a given scientist. N Brown, E Jacoby, On
scaffolds and hopping in medicinal chemistry. Mini Rev Med Chem 6
(11) :1217- 1229, Nov 2006. Related term: scaffold
hopping
natural
products:
http://en.wikipedia.org/wiki/Natural_products Related terms: Biomaterials
biomimetic materials, biomimetics
organic
chemistry: The role played by organic chemistry
in the pharmaceutical industry continues to be one of the main drivers in the
drug discovery process. However, the precise nature of that role is undergoing a
visible change, not only because of the new synthetic methods and technologies
now available to the synthetic and medicinal chemist, but also in several key
areas, particularly in drug metabolism and chemical toxicology, as chemists deal
with the ever more rapid turnaround of testing data that influences their day-
to- day decisions. M MacCoss, TA Baillie, Organic
chemistry in drug discovery, Science 303 (5665): 1810- 1813, Mar. 19, 2004
NIST, Organic Electronics
https://www.nist.gov/topics/organic-electronics
oxygen radicals:
There are many types of radicals, but those of most concern in biological
systems are derived from oxygen, and known collectively as reactive oxygen
species. Oxygen has two unpaired electrons in separate orbitals in its
outer shell. This electronic structure makes oxygen especially susceptible
to radical formation… Biological Effects of Reactive Oxygen It is best not
to think of oxygen radicals as "bad". They are generated in a number of
reactions essential to life… There is also a large body evidence
indicating that oxygen radicals are involved in intercellular and
intracellular signalling. … Despite their beneficial activities, reactive
oxygen species clearly can be toxic to cells. By definition, radicals
possess an unpaired electron, which makes them highly reactive and thereby
able to damage all macromolecules, including lipids, proteins and nucleic
acids. R. Bowen, Colorado State University, Pathophysiology, Free
radicals and reactive oxygen
http://www.vivo.colostate.edu/hbooks/pathphys/topics/radicals.html
PAINS
Pan Assay Interference Compounds: A true drug inhibits or activates a
protein by fitting into a binding site on the protein.
Artefacts have subversive reactivity that masquerades as drug-like
binding and yields false signals across a variety of assays.
These molecules. have defined structures, covering several classes of
compounds. … But biologists and inexperienced chemists rarely recognize them.
.. Time and research money are consequently wasted in attempts to optimize the
activity of these compounds. Chemical con artists foil drug discovery, Jonathan
Baell, Michael A. Walters, Nature 513:
481-483, 25 Sept 2014 doi:
10.1038/513481a http://www.ncbi.nlm.nih.gov/pubmed/25254460
peptides:
Amides
derived from two or more amino carboxylic acid molecules (the same or
different) by formation of a covalent
bond from the carbonyl carbon of one to the nitrogen atom of another with
formal loss of water. The term is usually applied to structures formed from
α-amino acids, but it includes those derived from any amino carboxylic
acid. IUPAC http://goldbook.iupac.org/P04479.html
Members of the class of compounds composed of
AMINO ACIDS joined together by peptide bonds between adjacent amino acids into
linear, branched or cyclical structures. OLIGOPEPTIDES are composed of
approximately 2-12 amino acids. Polypeptides are composed of approximately 13
or more amino acids. PROTEINS are linear polypeptides that are normally
synthesized on RIBOSOMES. MeSH
peptidomimetic:
A compound containing ono- peptidic structural elements that is capable of mimicking or antagonizing
the biological action (s) of a natural parent peptide. A peptidomimetic
does no longer have classical peptide characteristics such as enzymatic
ally scissile peptic bonds. IUPAC Medicinal Chemistry Related terms: -Omes &
-omics peptidome,
peptidomics
Wikipedia
http://en.wikipedia.org/wiki/Peptidomimetic
privileged structures:
Privileged
structures are defined as molecular frameworks which are able of providing
useful ligands for more than one type of receptor or enzyme target by
judicious structural modification.
Privileged
structures: a useful concept for the rational design of new lead drug
candidates.
Duarte
CD1, Barreiro
EJ, Fraga
CA. Mini
Rev Med Chem. 2007 Nov;7(11):1108-19. http://www.ncbi.nlm.nih.gov/pubmed/18045214
The concept of so-called "privileged
structures" was initially proposed by scientists at Merck in 1980s (see
ref. Journal of Medicinal Chemistry, 31, 2235-2246, 1988). They observed in
their research at Merck that certain type of structures were preferred by
certain class of receptors (proteins). ... It appears that the main function
of the privileged structure in a drug molecule is to position those functional
groups that are attached to it in a right direction and help them interact
with the receptor properly. Therefore, it's logical to think that by replacing
the privileged structure of a drug molecule while keeping those functional
groups unchanged, we might find a better drug. Shanghai Syncores
Technologies Inc. http://www.syncores.net/priviledged.htm
racemate:
An equimolar mixture of a pair of enantiomers.
It does not exhibit optical activity. The chemical name or formula of a racemate
is distinguished from those of the enantiomers by the prefix (±)- or rac- (or
racem-) or by the symbols RS and SR. IUPAC Compendium Related term: enantiomer
reagents:
In the field of biology,
the biotechnology revolution
in the 1980s grew from the development of reagents that could be used to
identify and manipulate the chemical matter in and on cells.[2][3] These
reagents included antibodies (polyclonal and monoclonal), oligomers,
all sorts of organisms and immortalised
cell lines, reagents and methods for molecular
cloning and DNA
replication, and many others.[3][4]
Tool compounds
are also important reagents in biology; they are small molecules or
biochemicals like siRNA or antibodies that
are known to affect a given biomolecule—for example a drug
target—but are unlikely to be useful
as drugs themselves, and are often starting points in the drug
discovery process.[5][6] Many
natural products, such as curcumin,
are hits in almost any assay in which they are tested, are not useful tool
compounds, and are classified by medicinal chemists as "pan-assay
interference compounds".[7][8][9]
Wikipedia accessed 2018 Nov 10
https://en.wikipedia.org/wiki/Reagent#Biology
reverse
[chemical] genetics: See under forward [chemical] genetics
reverse
chemical proteomics:
The proteome is expressed on the surface of an
amplifiable vector and then probed with a tagged small molecule. The only
example currently available is display cloning, using phage display of a cDNA
library (transcriptome) and panning this library with a small molecule probe
(drug or natural product). Andrew M. Piggott and Peter Karuso, Quality Not
Quantity: The Role of Natural Products and Chemical Proteomics in Modern Drug
Discovery, Combinatorial Chemistry and High Throughput Screening, 7(7): 607-
630. 2004
Related terms: forward chemical
genetics; reverse genetics, reverse genomics
scaffold
hopping: the definition of scaffold hopping
and, more importantly, the detection of what constitutes a scaffold hop, is also
ill-defined and highly subjective. Essentially, it is agreed that scaffolds
should be substantially different from each other, although significantly
similar to each other, to constitute a hop. In the latter, the scaffolds must
permit a similar geometric arrangement of functional groups to permit the mode
of action. However, this leaves the paradox of how to describe both scaffold
similarity and dissimilarity simultaneously. In this paper, the current statuses
of scaffolds and scaffold hopping are reviewed based on published examples of
scaffold hopping from the literature. An investigation of the degree to which it
is possible to formulate a more rigorous definition of scaffolds and hopping in
the context of molecular topologies is considered. N Brown, E Jacoby, On
scaffolds and hopping in medicinal chemistry. Mini Rev Med Chem 6 (11)
:1217- 1229, Nov 2006 Related term: molecular
scaffold.
A primary goal of 3D similarity searching is to find
compounds with similar bioactivity to a reference ligand but with different
chemotypes, i.e., "scaffold hopping". However, an adequate description
of chemical structures in 3D conformational space is difficult due to the high-
dimensionality of the problem. We present an automated method that simplifies
flexible 3D chemical descriptions in which clustering techniques traditionally
used in data mining are exploited to create "fuzzy" molecular
representations called FEPOPS (feature point pharmacophores). A
3D similarity method for scaffold hopping from known drugs or natural ligands to
new chemotypes, JL Jenkins, M Glick, JW Davies Journal of Medicinal
Chemistry 47 (25): 6144- 6159, Dec. 2, 2004 Related terms?:
molecular scaffold, Assays lead hopping, target
hopping
small
molecules: Drug
discovery & development; small
molecule libraries
solubility:
SOLUBILITY is one of the most basic and important of
thermodynamic properties, and a property which underlies most industrial
processes. This book is a collection of 24 chapters involving recent research
works, all related to solubility. The objective is to bring together research
from disparate disciplines which have a bearing on solubility. Links between
these chapters, we believe, could lead to new ways of solving problems and
looking at new and also old solubility related issues.
Developments
and Applications in Solubility,
Trevor M. Letcher (ed.) The
Royal Society of Chemistry, 2006
[ISBN
0 85404 372 1; ISBN-13 978 0
85404 372 9]
http://old.iupac.org/publications/books/author/letcher07.html
structural
chemogenomics
As structure determination provides an increasingly complete
three dimensional and functional view of genomic biology, various approaches
will be utilized to identify selective small molecule ligands for
proteins on a
genomic scale. This will be defined as "structural
chemogenomics" and will undoubtedly provide new opportunities for drug
development as new synthetic chemistries develop, computational tools advance,
and protein families are understood at the atomic level. Sara Dry et. al
"Structural genomics in the biotechnology sector" Nature
Structural Biology supplement 7:946 - 949, Nov. 2000
systems
chemical biology: The
integration of chemistry, biology and computation to generate understanding
about the way small molecules affect biological systems as a whole. Systems
chemical biology and the Semantic Web: what they mean for the future of drug
discovery research.
David
J. Wild, Ying Ding,
Amit P. Sheth , Lee
Harland, Eric M. Gifford, Michael
S. Lajiness , Drug Discovery Today, January 2012
http://lists.w3.org/Archives/Public/public-semweb-lifesci/2012Jan/att-0020/Wild_2012_SystemsBioSW.pdf
tool compounds: Tool compounds usually
constitute drug candidates with limited potential,
either due to limited IP protection or limited application in humans.
Despite their reduced potential as final drug candidate they represent a
valuable tool for early
drug discovery, early target validation and proof-of-concept studies. We
are currently using such tool compounds to
investigate the druggability and target validation of developmental
transcription factors in the treatment of solid tumours, and intra
cellular and membrane-bound receptors for the modulation of inflammatory
responses. Cooper Group, University of Queensland, Australia http://cooper.imb.uq.edu.au/research_drug_discovery.html
Small
molecular weight compounds of
known structure from the literature that are not commercially available.
Center for Integrative Chemical Biology and Drug Discovery, University of
North Carolina Chapel Hill
http://cicbdd.web.unc.edu/resources/request-a-tool-compound/
Related term: chemical tools
Chemistry resources
Chemistry Conferences
http://www.healthtech.com/conferences/upcoming.aspx?s=CHM
Drug Discovery Chemistry
https://www.drugdiscoverychemistry.com/
about.com Chemistry Glossary, about 200 terms http://chemistry.about.com/library/glossary/blglossary.htm
IUPAC
Compendium of Chemical Terminology Gold Book
https://goldbook.iupac.org/
IUPAC International Union of Pure and
Applied Chemistry, Glossary of Terms used in Bioinorganic Chemistry,
Recommendations, 1997. 450+ definitions.
http://www.chem.qmw.ac.uk/iupac/bioinorg/
IUPAC International Union of Pure and Applied
Chemistry, Glossary for Chemists of terms used in biotechnology.
Recommendations, Pure & Applied Chemistry 64 (1): 143-168, 1992. 200 +
definitions.
IUPAC International Union of Pure and
Applied Chemistry, Glossary of Terms Used in Combinatorial Chemistry, D.
Maclean, J. J. Baldwin, V.T. Ivanov, Y. Kato, A. Shaw, P. Schneider, and E. M..
Gordon, Pure Appl. Chem., Vol. 71, No. 12, pp. 2349-2365, 1999. 100+
definitions. http://www.iupac.org/reports/1999/7112maclean/
IUPAC Inernational Union of Pure and Applied Chemistry, Glossary of terms
used in Computational Drug Design Part II, 2015
https://www.degruyter.com/view/j/pac.1997.69.issue-5/pac199769051137/pac199769051137.xml
IUPAC International Union of Pure and Applied Chemistry, Glossary of terms
used in Medicinal Chemistry, Part 1, 1998
https://www.iupac.org/publications/pac/pdf/1998/pdf/7005x1129.pdf
IUPAC International Union of Pure and Applied Chemistry, Glossary of terms
used in Medicinal Chemistry. Part II (IUPAC Recommendations 2013
https://www.iupac.org/publications/pac/pdf/2013/pdf/8508x1725.pdf
IUPAC International Union of Pure and Applied
Chemistry, Glossary of Terms used in Photochemistry,
3rd ed. 2006
http://iupac.org/publications/pac/79/3/0293/
IUPAC International Union of Pure and Applied
Chemistry, Glossary of Terms used in Physical Organic Chemistry, Recommendations
1994. 700+ definitions. Part of OneLook.
https://www.qmul.ac.uk/sbcs/iupac/gtpoc/
IUPAC International Union of Pure and Applied
Chemistry, Glossary of Terms in Quantities and Units in Clinical Chemistry,
Biochim Clin 1995; 19: 471-502. Around 300 definitions Pure & Applied
Chemistry 68: 957- 1000, 1996
IUPAC International Union of Pure and Applied
Chemistry, Basic Terminology of Stereochemistry Recommendations, 1996. 250+
definitions
https://www.degruyter.com/view/IUPAC/iupac.68.3330
IUPAC International Union of Pure and Applied Chemistry, GLOSSARY FOR
CHEMISTS OF TERMS USED IN TOXICOLOGY Clinical Chemistry
Division, Commission on Toxicology, Recommendations. Pure and Appl. Chem.,
65 ( 9): 2003-2122, 1993. 1200+ definitions. https://www.degruyter.com/view/IUPAC/iupac.65.0047
IUPAC International
Union of Pure and Applied Chemistry, Nomenclature in laboratory robotics and
automation, 1994 http://www.iupac.org/publications/pac/1994/pdf/6603x0609.pdf
IUPAC International
Union of Pure and Applied Chemistry, Postgenomic Chemistry Pure and
Applied Chemistry 77 (9) , 1641 - 1654, 2005
https://www.iupac.org/publications/pac/77/9/1641/index.html
IUPAC,
Glossary of terms used in theoretical organic chemistry, 1999 http://www.iupac.org/publications/pac/1999/71_10_pdf/7110mirkin_1919.pdf
Oxford Dictionary of Biochemistry
and Molecular Biology, Oxford University Press,
Royal Society of Chemistry, RSC ontologies http://www.rsc.org/ontologies/
Name Reaction Ontology RXNO, Chemical Methods Ontology CMO, Molecular
Processes Ontology MOP
How
to look for other unfamiliar terms
IUPAC
definitions are reprinted with the permission of the International Union of Pure
and Applied Chemistry.
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