Within the fields of
molecular biology and
pharmacology, a small molecule or micromolecule is a low molecular weight (≤ 1000
daltons)
organic compound that may regulate a biological process, with a size on the order of 1 nm. Many
drugs are small molecules; the terms are equivalent in the literature.
Larger structures such as
nucleic acids and
proteins, and many
polysaccharides are not small molecules, although their constituent monomers (ribo- or deoxyribonucleotides,
amino acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...
s, and monosaccharides, respectively) are often considered small molecules. Small molecules may be used as research tools to probe
biological function
In evolutionary biology, function is the reason some object or process occurred in a system that evolved through natural selection. That reason is typically that it achieves some result, such as that chlorophyll helps to capture the energy of sunl ...
as well as
leads
Lead is a chemical element with symbol Pb and atomic number 82.
Lead or The Lead may also refer to:
Animal handling
* Leash, or lead
* Lead (leg), the leg that advances most in a quadruped's cantering or galloping stride
* Lead (tack), a lin ...
in the development of new
therapeutic agents. Some can inhibit a specific function of a protein or disrupt
protein–protein interactions.
Pharmacology usually restricts the term "small molecule" to molecules that bind specific biological
macromolecules and act as an
effector
Effector may refer to:
*Effector (biology), a molecule that binds to a protein and thereby alters the activity of that protein
* ''Effector'' (album), a music album by the Experimental Techno group Download
* ''EFFector'', a publication of the El ...
, altering the activity or function of the
target
Target may refer to:
Physical items
* Shooting target, used in marksmanship training and various shooting sports
** Bullseye (target), the goal one for which one aims in many of these sports
** Aiming point, in field artillery, fi ...
. Small molecules can have a variety of biological functions or applications, serving as
cell signaling
In biology, cell signaling (cell signalling in British English) or cell communication is the ability of a cell to receive, process, and transmit signals with its environment and with itself. Cell signaling is a fundamental property of all cellula ...
molecules,
drugs in
medicine,
pesticides in farming, and in many other roles. These compounds can be natural (such as
secondary metabolites
Secondary metabolites, also called specialised metabolites, toxins, secondary products, or natural products, are organic compounds produced by any lifeform, e.g. bacteria, fungi, animals, or plants, which are not directly involved in the norma ...
) or artificial (such as
antiviral drug
Antiviral drugs are a class of medication used for treating viral infections. Most antivirals target specific viruses, while a broad-spectrum antiviral is effective against a wide range of viruses. Unlike most antibiotics, antiviral drugs do ...
s); they may have a beneficial effect against a disease (such as
drugs) or may be detrimental (such as
teratogens and
carcinogen
A carcinogen is any substance, radionuclide, or radiation that promotes carcinogenesis (the formation of cancer). This may be due to the ability to damage the genome or to the disruption of cellular metabolic processes. Several radioactive substa ...
s).
Molecular weight cutoff
The upper
molecular-weight limit for a small molecule is approximately 900 daltons, which allows for the possibility to rapidly diffuse across cell membranes so that it can reach
intracellular
This glossary of biology terms is a list of definitions of fundamental terms and concepts used in biology, the study of life and of living organisms. It is intended as introductory material for novices; for more specific and technical definitions ...
sites of action.
This molecular weight cutoff is also a necessary but insufficient condition for oral
bioavailability
In pharmacology, bioavailability is a subcategory of absorption and is the fraction (%) of an administered drug that reaches the systemic circulation.
By definition, when a medication is administered intravenously, its bioavailability is 100%. H ...
as it allows for
transcellular transport through intestinal
epithelial
Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellula ...
cells. In addition to intestinal permeability, the molecule must also possess a reasonably rapid
rate of dissolution into water and adequate water
solubility and moderate to low
first pass metabolism. A somewhat lower molecular weight cutoff of 500 daltons (as part of the "
rule of five
Lipinski's rule of five, also known as Pfizer's rule of five or simply the rule of five (RO5), is a rule of thumb to evaluate druglikeness or determine if a chemical compound with a certain pharmacological or biological activity has chemical pro ...
") has been recommended for oral small molecule drug candidates based on the observation that clinical attrition rates are significantly reduced if the molecular weight is kept below this limit.
Drugs
Most pharmaceuticals are small molecules, although some drugs can be proteins (e.g.,
insulin and other
biologic medical product
A biopharmaceutical, also known as a biological medical product, or biologic, is any pharmaceutical drug product manufactured in, extracted from, or semisynthesized from biological sources. Different from totally synthesized pharmaceuticals, th ...
s). With the exception of
therapeutic antibodies
Monoclonal antibody therapy is a form of immunotherapy that uses monoclonal antibodies (mAbs) to bind monospecifically to certain cells or proteins. The objective is that this treatment will stimulate the patient's immune system to attack those ...
, many proteins are degraded if administered orally and most often cannot cross
cell membranes. Small molecules are more likely to be absorbed, although some of them are only absorbed after oral administration if given as
prodrugs. One advantage that small molecule drugs (SMDs) have over "large molecule"
biologics is that many small molecules can be taken orally whereas biologics generally require injection or another
parenteral
A route of administration in pharmacology and toxicology is the way by which a drug, fluid, poison, or other substance is taken into the body.
Routes of administration are generally classified by the location at which the substance is applied. ...
administration.
Secondary metabolites
A variety of organisms including bacteria, fungi, and plants, produce small molecule
secondary metabolite
Secondary metabolites, also called specialised metabolites, toxins, secondary products, or natural products, are organic compounds produced by any lifeform, e.g. bacteria, fungi, animals, or plants, which are not directly involved in the norm ...
s also known as
natural products, which play a role in cell signaling, pigmentation and in defense against predation. Secondary metabolites are a rich source of biologically active compounds and hence are often used as research tools and leads for drug discovery.
Examples of secondary metabolites include:
*
Alkaloids
Alkaloids are a class of basic, naturally occurring organic compounds that contain at least one nitrogen atom. This group also includes some related compounds with neutral and even weakly acidic properties. Some synthetic compounds of similar st ...
*
Glycosides
In chemistry, a glycoside is a molecule in which a sugar is bound to another functional group via a glycosidic bond. Glycosides play numerous important roles in living organisms. Many plants store chemicals in the form of inactive glycosides. ...
*
Lipids
*
Nonribosomal peptides, such as
actinomycin-D
*
Phenazines
*
Natural phenol
In biochemistry, naturally occurring phenols are natural products containing at least one phenol functional group. Phenolic compounds are produced by plants and microorganisms. Organisms sometimes synthesize phenolic compounds in response to ecol ...
s (including
flavonoids)
*
Polyketide
*
Terpenes
Terpenes () are a class of natural products consisting of compounds with the formula (C5H8)n for n > 1. Comprising more than 30,000 compounds, these unsaturated hydrocarbons are produced predominantly by plants, particularly conifers. Terpenes ar ...
, including
steroid
A steroid is a biologically active organic compound with four rings arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes that alter membrane fluidity; and ...
s
*
Tetrapyrroles
Tetrapyrroles are a class of chemical compounds that contain four pyrrole or pyrrole-like rings. The pyrrole/pyrrole derivatives are linked by ( =- or -- units), in either a linear or a cyclic fashion. Pyrroles are a five-atom ring with four car ...
.
Research tools
Enzymes and receptors are often activated or inhibited by
endogenous protein, but can be also inhibited by endogenous or exogenous
small molecule inhibitors or
activators, which can bind to the
active site
In biology and biochemistry, the active site is the region of an enzyme where substrate molecules bind and undergo a chemical reaction. The active site consists of amino acid residues that form temporary bonds with the substrate (binding site) ...
or on the
allosteric site
In biochemistry, allosteric regulation (or allosteric control) is the regulation of an enzyme by binding an effector molecule at a site other than the enzyme's active site.
The site to which the effector binds is termed the ''allosteric site ...
.
An example is the teratogen and carcinogen
phorbol 12-myristate 13-acetate, which is a plant terpene that activates
protein kinase C, which promotes cancer, making it a useful investigative tool.
There is also interest in creating small molecule
artificial transcription factors to regulate
gene expression, examples include wrenchnolol (a wrench shaped molecule).
Binding of
ligand can be characterised using a variety of analytical techniques such as
surface plasmon resonance,
microscale thermophoresis
Microscale thermophoresis (MST) is a technology for the biophysical analysis of interactions between biomolecules. Microscale thermophoresis is based on the detection of a temperature-induced change in fluorescence of a target as a function of th ...
or
dual polarisation interferometry to quantify the reaction affinities and kinetic properties and also any induced
conformational change
In biochemistry, a conformational change is a change in the shape of a macromolecule, often induced by environmental factors.
A macromolecule is usually flexible and dynamic. Its shape can change in response to changes in its environment or othe ...
s.
Anti-genomic therapeutics
Small-molecule
anti-genomic therapeutics, or SMAT, refers to a
biodefense
Biodefense refers to measures to restore biosecurity to a group of organisms who are, or may be, subject to biological threats or infectious diseases. Biodefense is frequently discussed in the context of biowar or bioterrorism, and is generall ...
technology that targets
DNA signatures found in many
biological warfare
Biological warfare, also known as germ warfare, is the use of biological toxins or infectious agents such as bacteria, viruses, insects, and fungi with the intent to kill, harm or incapacitate humans, animals or plants as an act of war. B ...
agents. SMATs are new, broad-spectrum drugs that unify antibacterial, antiviral and anti-malarial activities into a single therapeutic that offers substantial cost benefits and logistic advantages for physicians and the military.
See also
*
Pharmacology
*
Druglikeness
Druglikeness is a qualitative concept used in drug design for how "druglike" a substance is with respect to factors like bioavailability. It is estimated from the molecular structure before the substance is even synthesized and tested. A druglike m ...
*
Lipinski's rule of five
Lipinski's rule of five, also known as Pfizer's rule of five or simply the rule of five (RO5), is a rule of thumb to evaluate druglikeness or determine if a chemical compound with a certain pharmacological or biological activity has chemical pro ...
*
Metabolite
In biochemistry, a metabolite is an intermediate or end product of metabolism.
The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, c ...
*
Chemogenomics
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 iden ...
*
Neurotransmitter
*
Peptidomimetic
A peptidomimetic is a small protein-like chain designed to mimic a peptide. They typically arise either from modification of an existing peptide, or by designing similar systems that mimic peptides, such as peptoids and β-peptides. Irrespectiv ...
*
Macromolecule
References
External links
* {{MeSH name, Small+Molecule+Libraries
Plant physiology
Drug discovery
Induced stem cells