Within the fields of molecular biology and pharmacology, a small molecule is a low molecular
weight (< 900 daltons) organic compound that may regulate a biological process, with a
size on the order of 1 nm.
Many drugs are small molecules.
Larger structures such as nucleic acids and proteins, and many polysaccharides are not
small molecules, although their constituent monomers (ribo- or deoxyribonucleotides, amino
acids, and monosaccharides, respectively) are often considered small molecules.
Small molecules may be used as research tools to probe biological function as well as leads
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, altering the activity or function of the target.
Small molecules can have a variety of biological functions or applications, serving as cell
signaling molecules, drugs in medicine, pesticides in farming, and in many other roles.
These compounds can be natural (such as secondary metabolites) or artificial (such as antiviral
drugs); they may have a beneficial effect against a disease (such as drugs) or may be
detrimental (such as teratogens and carcinogens).
== 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 sites of action.
This molecular weight cutoff is also a necessary but insufficient condition for oral bioavailability
as it allows for transcellular transport through intestinal epithelial 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")
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 products).
With the exception of therapeutic antibodies, 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 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 administration.
== Secondary metabolites == A variety of organisms including bacteria,
fungi, and plants, produce small molecule secondary metabolites 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:
== 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 or on 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 or dual polarisation interferometry to quantify the reaction affinities
and kinetic properties and also any induced conformational changes.
== Anti-genomic therapeutics == Small-molecule anti-genomic therapeutics,
or SMAT, refers to a biodefense technology that targets DNA signatures found in many
biological warfare 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
Metabolite Chemogenomics
Neurotransmitter Peptidomimetic