# Small molecule > Mediated Wiki article. Canonical URL: https://mediated.wiki/source/Small_molecule > Markdown URL: https://mediated.wiki/source/Small_molecule.md > Source: https://en.wikipedia.org/wiki/Small_molecule > Source revision: 1352064356 > License: Creative Commons Attribution-ShareAlike 4.0 International (https://creativecommons.org/licenses/by-sa/4.0/) Organic molecule weighing under 1000 daltons In [molecular biology](/source/Molecular_biology) and [pharmacology](/source/Pharmacology), a **small molecule** or **micromolecule** is a low molecular weight (≤ 1000 [daltons](/source/Dalton_(unit)))[1] [organic compound](/source/Organic_compound) that may regulate a biological process, with a size on the order of 1 nm.[*[citation needed](https://en.wikipedia.org/wiki/Wikipedia:Citation_needed)*] [Larger structures](/source/Macromolecule) such as [nucleic acids](/source/Nucleic_acid) and [proteins](/source/Protein), and many [polysaccharides](/source/Polysaccharides) are not small molecules, although their constituent monomers (ribo- or deoxyribonucleotides, [amino acids](/source/Amino_acid), and monosaccharides, respectively) are often considered small molecules. Small molecules may be used as research tools to probe [biological function](/source/Function_(biology)) as well as [leads](/source/Lead_compound) in the development of new [therapeutic agents](/source/Pharmaceutical_drug). Some can inhibit a specific function of a protein or disrupt [protein–protein interactions](/source/Protein%E2%80%93protein_interaction).[2] [Pharmacology](/source/Pharmacology) usually restricts the term "small molecule" to molecules that bind specific biological [macromolecules](/source/Macromolecules) and act as an [effector](/source/Effector_(biology)), altering the activity or function of the [target](/source/Biological_target). Small molecules can have a variety of biological functions or applications, serving as [cell signaling](/source/Cell_signaling) molecules, [drugs](/source/Drug) in [medicine](/source/Medicine), [pesticides](/source/Pesticide) in farming, and in many other roles. These compounds can be natural (such as [secondary metabolites](/source/Secondary_metabolites)) or artificial (such as [antiviral drugs](/source/Antiviral_drug)); they may have a beneficial effect against a disease (such as [drugs](/source/Pharmaceuticals)) or may be detrimental (such as [teratogens](/source/Teratogen) and [carcinogens](/source/Carcinogen)). ## Molecular weight cutoff The upper [molecular-weight](/source/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](/source/Intracellular) sites of action.[1][3] This molecular weight cutoff is also a necessary but insufficient condition for oral [bioavailability](/source/Bioavailability) as it allows for [transcellular transport](/source/Transcellular_transport) through intestinal [epithelial](/source/Epithelial) cells. In addition to intestinal permeability, the molecule must also possess a reasonably rapid [rate of dissolution](/source/Dissolution_(chemistry)#Rate_of_dissolution) into water and adequate water [solubility](/source/Solubility) and moderate to low [first pass metabolism](/source/First_pass_metabolism). A somewhat lower molecular weight cutoff of 500 daltons (as part of the "[rule of five](/source/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.[4][5] ## Drugs Further information: [Pharmaceutical drug](/source/Pharmaceutical_drug) and [Targeted therapy](/source/Targeted_therapy) Most pharmaceuticals are small molecules, although some drugs can be proteins (*e.g.*, [insulin](/source/Insulin) and other [biologic medical products](/source/Biologic_medical_product)). With the exception of [therapeutic antibodies](/source/Monoclonal_antibody_therapy), many proteins are degraded if administered orally and most often cannot cross [cell membranes](/source/Cell_membrane). Small molecules are more likely to be absorbed, although some of them are only absorbed after oral administration if given as [prodrugs](/source/Prodrug). One advantage that **small-molecule drugs** (SMDs) have over "large-molecule" [biologics](/source/Biologic_medical_product) is that many small molecules can be taken orally whereas biologics generally require injection or another [parenteral](/source/Parenteral) administration.[6] 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](/source/Cancers) are often resistant to their effects.[7] ## Secondary metabolites A variety of organisms including bacteria, fungi, and plants, produce small molecule [secondary metabolites](/source/Secondary_metabolite) also known as [natural products](/source/Natural_product), 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.[8] Examples of secondary metabolites include: - [Alkaloids](/source/Alkaloids) - [Glycosides](/source/Glycosides) - [Lipids](/source/Lipids) - [Nonribosomal peptides](/source/Nonribosomal_peptide), such as [actinomycin-D](/source/Actinomycin-D) - [Phenazines](/source/Phenazines) - [Natural phenols](/source/Natural_phenol) (including [flavonoids](/source/Flavonoid)) - [Polyketide](/source/Polyketide) - [Terpenes](/source/Terpenes) and [terpenoids](/source/Terpenoids), including [steroids](/source/Steroid) - [Tetrapyrroles](/source/Tetrapyrroles). ## Research tools Cell culture example of a small molecule as a tool instead of a protein. In [cell culture](/source/Cell_culture) to obtain a [pancreatic lineage](/source/Islets_of_Langerhans) from [mesodermal](/source/Mesoderm) [stem cells](/source/Stem_cells), the [retinoic acid](/source/Retinoic_acid) signaling pathway must be activated while the [sonic hedgehog](/source/Sonic_hedgehog) pathway inhibited, which can be done by adding to the [media](/source/Growth_medium) anti-shh [antibodies](/source/Antibodies), [Hedgehog interacting protein](/source/HHIP), or [cyclopamine](/source/Cyclopamine), where the first two molecules are proteins and the last a small molecule.[9] Enzymes and receptors are often activated or inhibited by [endogenous protein](/source/Ligand_(biochemistry)), but can be also inhibited by endogenous or exogenous [small molecule inhibitors](/source/Enzyme_inhibitor) or [activators](/source/Enzyme_inhibitor), which can bind to the [active site](/source/Active_site) or on the [allosteric site](/source/Allosteric_regulation).[*[citation needed](https://en.wikipedia.org/wiki/Wikipedia:Citation_needed)*] An example is the teratogen and carcinogen [phorbol 12-myristate 13-acetate](/source/Phorbol_12-myristate_13-acetate), which is a plant terpene that activates [protein kinase C](/source/Protein_kinase_C), which promotes cancer, making it a useful investigative tool.[10] There is also interest in creating small molecule [artificial transcription factors](/source/Artificial_transcription_factors) to regulate [gene expression](/source/Gene_expression), examples include wrenchnolol (a wrench shaped molecule).[11] Binding of [ligand](/source/Ligand_(biochemistry)) can be characterised using a variety of analytical techniques such as [surface plasmon resonance](/source/Surface_plasmon_resonance), [microscale thermophoresis](/source/Microscale_thermophoresis)[12] or [dual polarisation interferometry](/source/Dual_polarisation_interferometry) to quantify the reaction affinities and kinetic properties and also any induced [conformational changes](/source/Conformational_change). ## Anti-genomic therapeutics **Small-molecule [anti-genomic](/source/Antigenome) therapeutics**, or SMAT, refers to a [biodefense](/source/Biodefense) technology that targets [DNA](/source/DNA) signatures found in many [biological warfare](/source/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.[13] ## See also - [Pharmacology](/source/Pharmacology) - [Druglikeness](/source/Druglikeness) - [Lipinski's rule of five](/source/Lipinski's_rule_of_five) - [Metabolite](/source/Metabolite) - [Chemogenomics](/source/Chemogenomics) - [Neurotransmitter](/source/Neurotransmitter) - [Peptidomimetic](/source/Peptidomimetic) - [Macromolecule](/source/Macromolecule) ## References 1. ^ [***a***](#cite_ref-Dougherty_Pucci_2012_1-0) [***b***](#cite_ref-Dougherty_Pucci_2012_1-1) Macielag MJ (2012). ["Chemical properties of antibacterials and their uniqueness"](https://books.google.com/books?id=av5SHPiHVcsC&q=oral%20drug%20molecular%20weight%20distribution%20antibiotics&pg=PA800). In Dougherty TJ, Pucci MJ (eds.). *Antibiotic Discovery and Development*. Springer. pp. 801–802. [ISBN](/source/ISBN_(identifier)) [978-1-4614-1400-1](https://en.wikipedia.org/wiki/Special:BookSources/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. 1. **[^](#cite_ref-pmid15060526_2-0)** Arkin MR, Wells JA (April 2004). "Small-molecule inhibitors of protein-protein interactions: progressing towards the dream". *Nature Reviews Drug Discovery*. **3** (4): 301–17. [doi](/source/Doi_(identifier)):[10.1038/nrd1343](https://doi.org/10.1038%2Fnrd1343). [PMID](/source/PMID_(identifier)) [15060526](https://pubmed.ncbi.nlm.nih.gov/15060526). [S2CID](/source/S2CID_(identifier)) [13879559](https://api.semanticscholar.org/CorpusID:13879559). 1. **[^](#cite_ref-pmid12036371_3-0)** Veber DF, Johnson SR, Cheng HY, Smith BR, Ward KW, Kopple KD (June 2002). "Molecular properties that influence the oral bioavailability of drug candidates". *J. Med. Chem*. **45** (12): 2615–23. [CiteSeerX](/source/CiteSeerX_(identifier)) [10.1.1.606.5270](https://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.606.5270). [doi](/source/Doi_(identifier)):[10.1021/jm020017n](https://doi.org/10.1021%2Fjm020017n). [PMID](/source/PMID_(identifier)) [12036371](https://pubmed.ncbi.nlm.nih.gov/12036371). 1. **[^](#cite_ref-4)** Lipinski CA (December 2004). "Lead-and drug-like compounds: the rule-of-five revolution". *Drug Discovery Today: Technologies*. **1** (4): 337–341. [doi](/source/Doi_(identifier)):[10.1016/j.ddtec.2004.11.007](https://doi.org/10.1016%2Fj.ddtec.2004.11.007). [PMID](/source/PMID_(identifier)) [24981612](https://pubmed.ncbi.nlm.nih.gov/24981612). 1. **[^](#cite_ref-pmid17971784_5-0)** Leeson PD, Springthorpe B (November 2007). "The influence of drug-like concepts on decision-making in medicinal chemistry". *Nature Reviews Drug Discovery*. **6** (11): 881–90. [doi](/source/Doi_(identifier)):[10.1038/nrd2445](https://doi.org/10.1038%2Fnrd2445). [PMID](/source/PMID_(identifier)) [17971784](https://pubmed.ncbi.nlm.nih.gov/17971784). [S2CID](/source/S2CID_(identifier)) [205476574](https://api.semanticscholar.org/CorpusID:205476574). 1. **[^](#cite_ref-Ganellin_2013_6-0)** Samanen J (2013). ["Chapter 5.2 How do SMDs differ from biomolecular drugs?"](https://books.google.com/books?id=342JY314Fl4C&q=small+molecule+vs+biologics+oral&pg=PA187). In Ganellin CR, Jefferis R, Roberts SM (eds.). *Introduction to Biological and Small Molecule Drug Research and Development: theory and case studies* (Kindle ed.). New York: Academic Press. pp. 161–203. [doi](/source/Doi_(identifier)):[10.1016/B978-0-12-397176-0.00005-4](https://doi.org/10.1016%2FB978-0-12-397176-0.00005-4). [ISBN](/source/ISBN_(identifier)) [978-0-12-397176-0](https://en.wikipedia.org/wiki/Special:BookSources/978-0-12-397176-0). Table 5.13: Route of Administration: Small Molecules: oral administration usually possible; Biomolecules: Usually administered parenterally 1. **[^](#cite_ref-7)** Ngo, Huy X.; Garneau-Tsodikova, Sylvie (23 April 2018). ["What are the drugs of the future?"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6072476). *MedChemComm*. **9** (5): 757–758. [doi](/source/Doi_(identifier)):[10.1039/c8md90019a](https://doi.org/10.1039%2Fc8md90019a). [ISSN](/source/ISSN_(identifier)) [2040-2503](https://search.worldcat.org/issn/2040-2503). [PMC](/source/PMC_(identifier)) [6072476](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6072476). [PMID](/source/PMID_(identifier)) [30108965](https://pubmed.ncbi.nlm.nih.gov/30108965). 1. **[^](#cite_ref-isbn978-0-444-53836-9_8-0)** Atta-ur-Rahman, ed. (2012). *Studies in Natural Products Chemistry*. Vol. 36. Amsterdam: Elsevier. [ISBN](/source/ISBN_(identifier)) [978-0-444-53836-9](https://en.wikipedia.org/wiki/Special:BookSources/978-0-444-53836-9). 1. **[^](#cite_ref-pmid17272496_9-0)** Mfopou JK, De Groote V, Xu X, Heimberg H, Bouwens L (May 2007). ["Sonic hedgehog and other soluble factors from differentiating embryoid bodies inhibit pancreas development"](https://doi.org/10.1634%2Fstemcells.2006-0720). *Stem Cells*. **25** (5): 1156–65. [doi](/source/Doi_(identifier)):[10.1634/stemcells.2006-0720](https://doi.org/10.1634%2Fstemcells.2006-0720). [PMID](/source/PMID_(identifier)) [17272496](https://pubmed.ncbi.nlm.nih.gov/17272496). [S2CID](/source/S2CID_(identifier)) [32726998](https://api.semanticscholar.org/CorpusID:32726998). 1. **[^](#cite_ref-isbn0-471-58651-X_10-0)** Voet JG, Voet D (1995). [*Biochemistry*](https://archive.org/details/biochemistry00voet_0). New York: J. Wiley & Sons. [ISBN](/source/ISBN_(identifier)) [978-0-471-58651-7](https://en.wikipedia.org/wiki/Special:BookSources/978-0-471-58651-7). 1. **[^](#cite_ref-pmid17894442_11-0)** Koh JT, Zheng J (September 2007). ["The new biomimetic chemistry: artificial transcription factors"](https://doi.org/10.1021%2Fcb700183s). *ACS Chem. Biol*. **2** (9): 599–601. [doi](/source/Doi_(identifier)):[10.1021/cb700183s](https://doi.org/10.1021%2Fcb700183s). [PMID](/source/PMID_(identifier)) [17894442](https://pubmed.ncbi.nlm.nih.gov/17894442). 1. **[^](#cite_ref-pmid20981028_12-0)** Wienken CJ, Baaske P, Rothbauer U, Braun D, Duhr S (2010). ["Protein-binding assays in biological liquids using microscale thermophoresis"](https://doi.org/10.1038%2Fncomms1093). *Nat Commun*. **1** (7) 100. [Bibcode](/source/Bibcode_(identifier)):[2010NatCo...1..100W](https://ui.adsabs.harvard.edu/abs/2010NatCo...1..100W). [doi](/source/Doi_(identifier)):[10.1038/ncomms1093](https://doi.org/10.1038%2Fncomms1093). [PMID](/source/PMID_(identifier)) [20981028](https://pubmed.ncbi.nlm.nih.gov/20981028). 1. **[^](#cite_ref-13)** Levine DS (2003). ["Bio-defense company re-ups"](http://www.bizjournals.com/sanfrancisco/stories/2003/04/28/story6.html). San Francisco Business Times. Retrieved September 6, 2006. ## External links - [Small+Molecule+Libraries](https://meshb.nlm.nih.gov/record/ui?name=Small+Molecule+Libraries) at the U.S. National Library of Medicine [Medical Subject Headings](/source/Medical_Subject_Headings) (MeSH) --- Adapted from the Wikipedia article [Small molecule](https://en.wikipedia.org/wiki/Small_molecule) by Wikipedia contributors ([contributor history](https://en.wikipedia.org/wiki/Small_molecule?action=history)). Available under [Creative Commons Attribution-ShareAlike 4.0 International](https://creativecommons.org/licenses/by-sa/4.0/). Changes may have been made.