MOTS-c — pharmacology
Molecular targets, mechanism of action, pharmacokinetics and interactions as characterised in humans.
§2Pharmacology
§2.1Molecular targets
Table 2. Molecular targets recorded for MOTS-c, with the character of the interaction and the potency where the Institute holds it.
| Target | Interaction | Note |
|---|---|---|
| AMP-activated protein kinase pathway | Indirect activation | Reported through folate-cycle and 5-aminoimidazole-4-carboxamide ribonucleotide accumulation rather than direct binding |
| Nuclear gene expression | Retrograde signalling | Reported translocation to the nucleus with effects on stress-response gene expression |
§2.2Mechanism of action
MOTS-c is described as a mitochondrial-encoded regulator of metabolic homeostasis that acts through the folate one-carbon cycle to raise 5-aminoimidazole-4-carboxamide ribonucleotide and thereby activate AMP-activated protein kinase, and separately as a retrograde signal translocating to the nucleus under metabolic stress. In rodent models it improves insulin sensitivity and reduces diet-induced obesity.[1,2]
§2.3Pharmacokinetics
No human pharmacokinetic characterisation of MOTS-c has been identified. In the absence of a half-life, a volume of distribution and a clearance estimate, no dosing interval used in practice can be related to any exposure that produced an effect in any study, and the Institute records this as a first-order gap rather than a detail.
§2.4Interactions
- Not characterised
References cited on this page
References are numbered in order of first citation in this document. Each superscript in the text links to its entry below.
- Lee C, Zeng J, Drew BG, Sallam T, Martin-Montalvo A, Wan J, Kim SJ, Mehta H, Hevener AL, de Cabo R, Cohen P. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metabolism 2015;21(3):443–454. doi:10.1016/j.cmet.2015.02.009 · PMID 25738459
- D’Hondt M, Bracke N, Taevernier L, Gevaert B, Verbeke F, Wynendaele E, De Spiegeleer B. Related impurities in peptide medicines. Journal of Pharmaceutical and Biomedical Analysis 2014;101:2–30. doi:10.1016/j.jpba.2014.06.012 · PMID 25044089
Identifiers are reproduced only where the Institute holds them. Where a digital object identifier or PubMed identifier is not shown, the Institute has recorded the journal and year and has not constructed an identifier.