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Small molecule

In molecular biology and pharmacology, a small molecule is a low molecular weight ( 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 they can reach intracellular sites of action. In addition, this molecular weight cutoff is a necessary but insufficient condition for oral bioavailability. Finally, a lower molecular weight cutoff of 500 daltons (as part of the " rule of five") has been recommended for small molecule drug development candidates based on the observation that clinical attrition rates are significantly reduced if the molecular weight is kept below this 500 dalton limit. Pharmacology usually restricts the term to a molecule that binds to a specific biological target—such as a specific protein or nucleic acid—and acts as an effector, altering the activity or function of the target. Small molecules can have a variety of biological functions, serving as cell signaling molecules, as drugs in medicine, as 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). Larger structures such as nucleic acids and proteins, and many polysaccharides (such as starch or cellulose), are not small molecules—though their constituent monomers (ribo- or deoxyribonucleotides, amino acids, and monosaccharides, respectively) are often considered small molecules. Very small oligomers are also usually considered small molecules, such as dinucleotides, peptides such as the antioxidant glutathione, and disaccharides such as sucrose. Small molecules may also 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 multifunctional protein or disrupt protein–protein interactions.


Most pharmaceuticals are small molecules, although some drugs can be proteins (e.g., insulin and other biologic medical products). 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 SMDs can be taken orally whereas biologics generally require injection or another parenteral administration.

Secondary metabolites

A wide variety of organisms including bacteria, fungi, and plants, produce small molecule secondary metabolites also known as natural products, which play a role in cell signalling, 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

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 change.

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


External links

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This article based upon the http://en.wikipedia.org/wiki/Small_molecule, the free encyclopaedia Wikipedia and is licensed under the GNU Free Documentation License.
Further informations available on the list of authors and history: http://en.wikipedia.org/w/index.php?title=Small_molecule&action=history
presented by: Ingo Malchow, Mirower Bogen 22, 17235 Neustrelitz, Germany