In molecular biology and pharmacology , a small molecule or micromolecule is a low molecular weight (≤ 1000 daltons ) organic compound that may regulate a biological process, with a size on the order of 1 nm . Many drugs are small molecules; the terms are equivalent in the literature. 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 .
21-524: SMAT may refer to: Small molecule anti-genomic therapeutics Santa Maria Area Transit Science Math Aptitude Test The School of Mission Aviation Technology, located at Ionia County Airport in Michigan Topics referred to by the same term [REDACTED] This disambiguation page lists articles associated with the title SMAT . If an internal link led you here, you may wish to change
42-563: A beneficial effect against a disease (such as drugs ) or may be detrimental (such as teratogens and carcinogens ). 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,
63-461: 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: 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
84-412: A single therapeutic that offers substantial cost benefits and logistic advantages for physicians and the military. Prodrug A prodrug is a pharmacologically inactive medication or compound that, after intake , is metabolized (i.e., converted within the body) into a pharmacologically active drug. Instead of administering a drug directly, a corresponding prodrug can be used to improve how
105-495: A transient manner to alter or to eliminate undesirable properties in the parent molecule. Many herbal extracts historically used in medicine contain glycosides (sugar derivatives) of the active agent, which are hydrolyzed in the intestines to release the active and more bioavailable aglycone . For example, salicin is a β-D-glucopyranoside that is cleaved by esterases to release salicylic acid . Aspirin , acetylsalicylic acid, first made by Felix Hoffmann at Bayer in 1897,
126-516: 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 changes . 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
147-464: Is a synthetic prodrug of salicylic acid. However, in other cases, such as codeine and morphine , the administered drug is enzymatically activated to form sugar derivatives (morphine- glucuronides ) that are more active than the parent compound. The first synthetic antimicrobial drug, arsphenamine , discovered in 1909 by Sahachiro Hata in the laboratory of Paul Ehrlich , is not toxic to bacteria until it has been converted to an active form by
168-533: Is kept below this limit. 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 that small molecule drugs (SMDs) have over "large molecule" biologics
189-492: Is one that is bioactivated at multiple sites, either in parallel or sequential steps. For example, a prodrug, which is bioactivated concurrently in both target cells and metabolic tissues, could be designated as a "Type IA/IB" prodrug (e.g., HMG Co-A reductase inhibitors and some chemotherapy agents; note the symbol " / " applied here). When a prodrug is bioactivated sequentially, for example initially in GI fluids then systemically within
210-538: 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. A variety of organisms including bacteria, fungi, and plants, produce small molecule secondary metabolites also known as natural products , which play
231-472: 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
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#1732793451268252-536: The body converts the prodrug into the final active drug form: Both major types can be further categorized into subtypes, based on factors such as (Type I) whether the intracellular bioactivation location is also the site of therapeutic action, or (Type 2) whether or not bioactivation occurs in the gastrointestinal fluids or in the circulation system. Type IA prodrugs include many antimicrobial and chemotherapy agents (e.g., 5-flurouracil). Type IB agents rely on metabolic enzymes, especially in hepatic cells, to bioactivate
273-402: The body. Likewise, prontosil , the first sulfa drug (discovered by Gerhard Domagk in 1932), must be cleaved in the body to release the active molecule, sulfanilamide . Since that time, many other examples have been identified. Terfenadine , the first non-sedating antihistamine , had to be withdrawn from the market because of the small risk of a serious side effect. However, terfenadine
294-736: The drug is absorbed, distributed, metabolized, and excreted ( ADME ). Prodrugs are often designed to improve bioavailability when a drug itself is poorly absorbed from the gastrointestinal tract . A prodrug may be used to improve how selectively the drug interacts with cells or processes that are not its intended target. This reduces adverse or unintended effects of a drug, especially important in treatments like chemotherapy , which can have severe unintended and undesirable side effects. Compound that undergoes biotransformation before exhibiting pharmacological effects. Note 1 : Modified from ref. Note 2 : Prodrugs can thus be viewed as drugs containing specialized nontoxic protective groups used in
315-418: The link to point directly to the intended article. Retrieved from " https://en.wikipedia.org/w/index.php?title=SMAT&oldid=991896695 " Category : Disambiguation pages Hidden categories: Short description is different from Wikidata All article disambiguation pages All disambiguation pages Small molecule anti-genomic therapeutics Pharmacology usually restricts
336-415: 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
357-854: The parent compound does not have the side effects associated with terfenadine, and so both loratadine and its active metabolite , desloratadine, are currently marketed. Approximately 10% of all marketed drugs worldwide can be considered prodrugs. Since 2008, at least 30 prodrugs have been approved by the FDA . Seven prodrugs were approved in 2015 and six in 2017. Examples of recently approved prodrugs are such as dabigatran etexilate (approved in 2010), gabapentin enacarbil (2011), sofosbuvir (2013), tedizolid phosphate (2014), isavuconazonium (2015), aripiprazole lauroxil (2015), selexipag (2015), latanoprostene bunod (2017), benzhydrocodone (2018), tozinameran (2020) and serdexmethylphenidate (2021). Prodrugs can be classified into two major types, based on how
378-469: The prodrugs intracellularly to active drugs. Type II prodrugs are bioactivated extracellularly, either in the milieu of GI fluids (Type IIA), within the systemic circulation and/or other extracellular fluid compartments (Type IIB), or near therapeutic target tissues/cells (Type IIC), relying on common enzymes such as esterases and phosphatases or target directed enzymes. Importantly, prodrugs can belong to multiple subtypes (i.e., Mixed-Type). A Mixed-Type prodrug
399-471: The target cells, it is designated as a "Type IIA-IA" prodrug (e.g., tenofovir disoproxil ; note the symbol " - " applied here). Many antibody- virus- and gene-directed enzyme prodrug therapies ( ADEPTs , VDEPTs , GDEPTs ) and proposed nanoparticle - or nanocarrier-linked drugs can understandably be Sequential Mixed-Type prodrugs. To differentiate these two Subtypes, the symbol dash " - " is used to designate and to indicate sequential steps of bioactivation, and
420-472: 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, drugs in medicine , 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
441-431: Was discovered to be the prodrug of the active molecule, fexofenadine , which does not carry the same risks as the parent compound. Therefore, fexofenadine could be placed on the market as a safe replacement for the original drug. Loratadine , another non-sedating antihistamine, is the prodrug of desloratadine , which is largely responsible for the antihistaminergic effects of the parent compound. However, in this case
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