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. Most 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.
1 Molecular weight cutoff 2 Drugs 3 Secondary metabolites 4 Research tools 5 Anti-genomic therapeutics 6 See also 7 References 8 External links
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 Further information: Pharmaceutical drug 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:
Alkaloids Glycosides Lipids Nonribosomal peptides, such as actinomycin-D Phenazines Natural phenols (including flavonoids) Polyketide Terpenes, including steroids Tetrapyrroles.
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
Small-molecule anti-genomic therapeutics, or SMAT, refers to a
biodefense technology that targets
Pharmacology Metabolite Chemogenomics Neurotransmitter Peptidomimetic
^ a b Macielag MJ (2012). "Chemical properties of antibacterials and
their uniqueness". In Dougherty TJ, Pucci MJ. Antibiotic Discovery and
Development. pp. 801–2. ISBN 978-1-4614-1400-1. The
majority of [oral] drugs from the general reference set have molecular
weights below 550. In contrast the molecular-weight distribution of
oral antibacterial agents is bimodal: 340–450 Da but with another
group in the 700–900 molecular weight range.
^ Arkin MR, Wells JA (April 2004). "Small-molecule inhibitors of
protein-protein interactions: progressing towards the dream". Nature
Small Molecule Libraries at the US National Library of Medicine Medical Subje