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Created page with "{{Short description|Organic molecule with a weight of ≤1000 daltons}} Within the fields of molecular biology and pharmacology, a '''small molecule''' or '''micromolecule''' is a low molecular weight (≤ 1000 daltons<ref name = "Dougherty_Pucci_2012">{{cite book |veditors=Dougherty TJ, Pucci MJ | title = Antibiotic Discovery and Development | year = 2012 | isbn = 978-1-4614-1400-1 | author = Macielag MJ | chapter = Chemical properties of a..."

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{{Short description|Organic molecule with a weight of ≤1000 daltons}}
Within the fields of [[molecular biology]] and [[pharmacology]], a '''small molecule''' or '''micromolecule''' is a low molecular weight (≤ 1000 [[Atomic mass unit|daltons]]<ref name = "Dougherty_Pucci_2012">{{cite book |veditors=Dougherty TJ, Pucci MJ | title = Antibiotic Discovery and Development | year = 2012 | isbn = 978-1-4614-1400-1 | author = Macielag MJ | chapter = Chemical properties of antibacterials and their uniqueness | pages = 801–2 | quote = 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. | chapter-url = https://books.google.com/books?id=av5SHPiHVcsC&q=oral%20drug%20molecular%20weight%20distribution%20antibiotics&pg=PA800 }}</ref>) [[organic compound]] that may regulate a biological process, with a size on the order of 1 nm{{Citation needed|date=June 2021}}. Many [[pharmaceuticals|drugs]] are small molecules; the terms are equivalent in the literature. [[macromolecule|Larger structures]] such as [[nucleic acid]]s and [[protein]]s, and many [[polysaccharides]] are not small molecules, although their constituent monomers (ribo- or deoxyribonucleotides, [[amino acid]]s, and monosaccharides, respectively) are often considered small molecules. Small molecules may be used as research tools to probe [[function (biology)|biological function]] as well as [[lead compound|leads]] in the development of new [[pharmaceutical drug|therapeutic agents]]. Some can inhibit a specific function of a protein or disrupt [[protein–protein interaction]]s.<ref name="pmid15060526">{{cite journal |vauthors=Arkin MR, Wells JA | title = Small-molecule inhibitors of protein-protein interactions: progressing towards the dream | journal = Nature Reviews Drug Discovery | volume = 3 | issue = 4 | pages = 301–17 |date=April 2004 | pmid = 15060526 | doi = 10.1038/nrd1343 | s2cid = 13879559 }}</ref>

[[Pharmacology]] usually restricts the term "small molecule" to molecules that bind specific biological [[macromolecules]] and act as an [[effector (biology)|effector]], altering the activity or function of the [[biological target|target]]. Small molecules can have a variety of biological functions or applications, serving as [[cell signaling]] molecules, [[drug]]s in [[medicine]], [[pesticide]]s in farming, and in many other roles. These compounds can be natural (such as [[secondary metabolites]]) or artificial (such as [[antiviral drug]]s); they may have a beneficial effect against a disease (such as [[pharmaceuticals|drugs]]) or may be detrimental (such as [[teratogen]]s and [[carcinogen]]s).

== Molecular weight cutoff ==
The upper [[Molecular mass|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.<ref name = "Dougherty_Pucci_2012"/><ref name="pmid12036371">{{cite journal |vauthors=Veber DF, Johnson SR, Cheng HY, Smith BR, Ward KW, Kopple KD | title = Molecular properties that influence the oral bioavailability of drug candidates | journal = J. Med. Chem. | volume = 45 | issue = 12 | pages = 2615–23 |date=June 2002 | pmid = 12036371 | doi = 10.1021/jm020017n | citeseerx = 10.1.1.606.5270 }}</ref> 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 [[Dissolution (chemistry)#Rate of dissolution|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.<ref>{{cite journal | author = Lipinski CA | title = Lead-and drug-like compounds: the rule-of-five revolution | journal = Drug Discovery Today: Technologies |date=December 2004 | volume = 1 | issue = 4 | pages = 337–341 | doi = 10.1016/j.ddtec.2004.11.007 | pmid = 24981612 }}</ref><ref name="pmid17971784">{{cite journal |vauthors=Leeson PD, Springthorpe B | title = The influence of drug-like concepts on decision-making in medicinal chemistry | journal = Nature Reviews Drug Discovery | volume = 6 | issue = 11 | pages = 881–90 |date=November 2007 | pmid = 17971784 | doi = 10.1038/nrd2445 | s2cid = 205476574 }}</ref>

==Drugs==
{{further|Pharmaceutical drug|Targeted therapy}}
Most pharmaceuticals are small molecules, although some drugs can be proteins (e.g., [[insulin]] and other [[biologic medical product]]s). With the exception of [[Monoclonal antibody therapy|therapeutic antibodies]], many proteins are degraded if administered orally and most often cannot cross [[cell membrane]]s. Small molecules are more likely to be absorbed, although some of them are only absorbed after oral administration if given as [[prodrug]]s. One advantage that '''small molecule drugs''' (SMDs) have over "large molecule" [[biologic medical product|biologics]] is that many small molecules can be taken orally whereas biologics generally require injection or another [[parenteral]] administration.<ref name="Ganellin_2013">{{cite book | author = Samanen J |veditors=Ganellin CR, Jefferis R, Roberts SM | title = Introduction to Biological and Small Molecule Drug Research and Development: theory and case studies | edition = Kindle | publisher = Academic Press | location = New York | year = 2013 | pages = 161–203| quote = Table 5.13: Route of Administration: Small Molecules: oral administration usually possible; Biomolecules: Usually administered parenterally | chapter-url = https://books.google.com/books?id=342JY314Fl4C&q=small+molecule+vs+biologics+oral&pg=PA187 | isbn = 978-0-12-397176-0 | chapter = Chapter 5.2 How do SMDs differ from biomolecular drugs? | doi = 10.1016/B978-0-12-397176-0.00005-4 }}</ref>

== Secondary metabolites ==
A variety of organisms including bacteria, fungi, and plants, produce small molecule [[secondary metabolite]]s also known as [[natural product]]s, 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.<ref name="isbn978-0-444-53836-9">{{cite book | editor = Atta-ur-Rahman | title = Studies in Natural Products Chemistry | volume = 36 | publisher = Elsevier | location = Amsterdam | year = 2012 | isbn = 978-0-444-53836-9 }}</ref> Examples of secondary metabolites include:
{{div col|colwidth=25em}}
*[[Alkaloids]]
*[[Glycosides]]
*[[Lipids]]
*[[Nonribosomal peptide]]s, such as [[actinomycin-D]]
*[[Phenazines]]
*[[Natural phenol]]s (including [[flavonoid]]s)
*[[Polyketide]]
*[[Terpenes]], including [[steroid]]s
*[[Tetrapyrroles]].
{{Div col end}}

== Research tools ==
[[Image:Regen2.svg|thumb|200px|Cell culture example of a small molecule as a tool instead of a protein. In [[cell culture]] to obtain a [[Islets of Langerhans|pancreatic lineage]] from [[mesoderm]]al [[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|media]] anti-shh [[antibodies]], [[HHIP|Hedgehog interacting protein]], or [[cyclopamine]], where the first two molecules are proteins and the last a small molecule.<ref name="pmid17272496">{{cite journal |vauthors=Mfopou JK, De Groote V, Xu X, Heimberg H, Bouwens L | title = Sonic hedgehog and other soluble factors from differentiating embryoid bodies inhibit pancreas development | journal = Stem Cells | volume = 25 | issue = 5 | pages = 1156–65 |date=May 2007 | pmid = 17272496 | doi = 10.1634/stemcells.2006-0720 | s2cid = 32726998 | doi-access = free }}</ref>]] Enzymes and receptors are often activated or inhibited by [[Ligand (biochemistry)|endogenous protein]], but can be also inhibited by endogenous or exogenous [[Enzyme inhibitor|small molecule inhibitors]] or [[Enzyme inhibitor|activators]], which can bind to the [[active site]] or on the [[Allosteric regulation|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.<ref name="isbn0-471-58651-X">{{cite book | vauthors = Voet JG, Voet D | title = Biochemistry | publisher = J. Wiley & Sons | location = New York | year = 1995 | isbn = 978-0-471-58651-7 | url-access = registration | url = https://archive.org/details/biochemistry00voet_0 }}</ref> There is also interest in creating small molecule [[artificial transcription factors]] to regulate [[gene expression]], examples include wrenchnolol (a wrench shaped molecule).<ref name="pmid17894442">{{cite journal |vauthors=Koh JT, Zheng J | title = The new biomimetic chemistry: artificial transcription factors | journal = ACS Chem. Biol. | volume = 2 | issue = 9 | pages = 599–601 |date=September 2007 | pmid = 17894442 | doi = 10.1021/cb700183s | doi-access = free }}</ref>

Binding of [[Ligand (biochemistry)|ligand]] can be characterised using a variety of analytical techniques such as [[surface plasmon resonance]], [[microscale thermophoresis]]<ref name="pmid20981028">{{cite journal |vauthors=Wienken CJ, Baaske P, Rothbauer U, Braun D, Duhr S | title = Protein-binding assays in biological liquids using microscale thermophoresis | journal = Nat Commun | volume = 1 | issue = 7| pages = 100 | year = 2010 | pmid = 20981028 | doi = 10.1038/ncomms1093 | bibcode = 2010NatCo...1..100W | doi-access = free }}</ref> or [[dual polarisation interferometry]] to quantify the reaction affinities and kinetic properties and also any induced [[conformational change]]s.

== Anti-genomic therapeutics ==
'''Small-molecule [[antigenome|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.<ref>{{cite web | author = Levine DS | year = 2003 | url = http://www.bizjournals.com/sanfrancisco/stories/2003/04/28/story6.html | title = Bio-defense company re-ups | publisher = San Francisco Business Times | access-date = September 6, 2006 }}</ref>

== See also ==
* [[Pharmacology]]
* [[Druglikeness]]
* [[Lipinski's rule of five]]
* [[Metabolite]]
* [[Chemogenomics]]
* [[Neurotransmitter]]
* [[Peptidomimetic]]
* [[Macromolecule]]
{{Clear}}

== References ==
{{reflist|35em}}

== External links ==
* {{MeSH name|Small+Molecule+Libraries}}

{{二次利用|date=2 October 2022}}
[[Category:Plant physiology]]
[[Category:Drug discovery]]
[[Category:Induced stem cells]]

Small molecule - Revision history