In molecular biology and pharmacology, a small molecule or micromolecule is a low molecular weight (≤ 1000 daltons
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, in medicine, in farming, and in many other roles. These compounds can be natural (such as secondary metabolites) or artificial (such as ); they may have a beneficial effect against a disease (such as pharmaceuticals) or may be detrimental (such as and ).
Molecular weight cutoff
The upper
Molecular mass 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
. Small molecules are more likely to be absorbed, although some of them are only absorbed after oral administration if given as
. 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 administration.
Small molecule drugs are also typically simpler to manufacture and cheaper for the purchaser. A downside is that not all targets are amenable to modification with small-molecule drugs; bacteria and
cancers are often resistant to their effects.
Secondary metabolites
A variety of organisms including bacteria, fungi, and plants, produce small molecule secondary metabolites also known as
, 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
to obtain a pancreatic lineage from
stem cells, the
retinoic acid signaling pathway must be activated while the
sonic hedgehog pathway inhibited, which can be done by adding to the
Growth medium anti-shh
antibodies,
HHIP, or
cyclopamine, where the first two molecules are proteins and the last a small molecule.
]] Enzymes and receptors are often activated or inhibited by endogenous protein, but can be also inhibited by endogenous or exogenous
Enzyme inhibitor or
Enzyme inhibitor, 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.
Binding of ligand can be characterised using a variety of analytical techniques such as surface plasmon resonance, microscale thermophoresis
Anti-genomic therapeutics
Small-molecule antigenome 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
External links
