OT-12

OT-12
Clinical data
Other namesOT-12; OT12
Routes of
administration		Subcutaneous injection
Drug classOxytocin receptor agonist
ATC code
  • None
Identifiers
  • 18-[[(1S)-5-[3-[2-[2-[3-[2-[2-[[2-[(2R)-3-[(2-amino-2-oxoethyl)amino]-2-[[(2S)-1-[(3R,6S,9S,12S,15S)-6-(2-amino-2-oxoethyl)-9-(3-amino-3-oxopropyl)-12-[(2R)-butan-2-yl]-15-[(4-hydroxyphenyl)methyl]-5,8,11,14,17-pentaoxo-1-thia-4,7,10,13,16-pentazacyclohenicosane-3-carbonyl]pyrrolidine-2-carbonyl]amino]-3-oxopropyl]sulfanylacetyl]amino]ethoxy]ethoxy]propanoylamino]ethoxy]ethoxy]propanoylamino]-1-carboxypentyl]amino]-18-oxooctadecanoic acid
PubChem CID
Chemical and physical data
FormulaC82H135N15O24S2
Molar mass1779.18 g·mol−1
3D model (JSmol)
  • CC[C@@H](C)[C@H]1C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CSCCCCC(=O)N[C@H](C(=O)N1)CC2=CC=C(C=C2)O)C(=O)N3CCC[C@H]3C(=O)N[C@@H](CSCC(=O)NCCOCCOCCC(=O)NCCOCCOCCC(=O)NCCCC[C@@H](C(=O)O)NC(=O)CCCCCCCCCCCCCCCCC(=O)O)C(=O)NCC(=O)N)CC(=O)N)CCC(=O)N
  • InChI=1S/C82H135N15O24S2/c1-3-55(2)74-80(114)92-58(32-33-65(83)99)76(110)93-61(50-66(84)100)77(111)95-63(53-122-48-21-19-26-71(105)91-60(78(112)96-74)49-56-28-30-57(98)31-29-56)81(115)97-39-22-24-64(97)79(113)94-62(75(109)89-51-67(85)101)52-123-54-72(106)88-38-43-121-47-45-119-41-35-69(103)87-37-42-120-46-44-118-40-34-68(102)86-36-20-18-23-59(82(116)117)90-70(104)25-16-14-12-10-8-6-4-5-7-9-11-13-15-17-27-73(107)108/h28-31,55,58-64,74,98H,3-27,32-54H2,1-2H3,(H2,83,99)(H2,84,100)(H2,85,101)(H,86,102)(H,87,103)(H,88,106)(H,89,109)(H,90,104)(H,91,105)(H,92,114)(H,93,110)(H,94,113)(H,95,111)(H,96,112)(H,107,108)(H,116,117)/t55-,58+,59+,60+,61+,62+,63+,64+,74+/m1/s1
  • Key:XYTFBZFZYWSYGY-BAROQLTRSA-N

OT-12 is a long-acting peripherally selective peptide oxytocin receptor agonist. It is a potent full agonist of the oxytocin receptor with comparable potency to oxytocin but with greater selectivity for the oxytocin receptor over the vasopressin receptors relative to oxytocin. The drug is highly peripherally selective similarly to oxytocin, with a brain-to-plasma ratio of about 1/190 or 0.5%. However, it shows much greater plasma protein binding and consequent metabolic stability compared to oxytocin. Whereas oxytocin has a plasma half-life of 2 to 3 minutes, OT-12 shows a terminal half-life with depot subcutaneous injection of 24 hours in rodents. It is thought that in humans the half-life of OT-12 by this route would be further much longer and could potentially allow for administration once every 1 to 2 weeks. Despite not crossing into the brain, OT-12 has been found to suppress food intake and decrease body weight when given by subcutaneous injection in rodents. The chemical synthesis of OT-12 has been described. OT-12 was first described in the scientific literature by Elsa Pflimlin and colleagues by 2020.

See also

References

  1. 1 2 3 4 5 6 7 8 9 10 Pflimlin E, Zhou Z, Amso Z, Fu Q, Lee C, Muppiddi A, et al. (January 2020). "Engineering a Potent, Long-Acting, and Periphery-Restricted Oxytocin Receptor Agonist with Anorexigenic and Body Weight Reducing Effects". Journal of Medicinal Chemistry. 63 (1): 382–390. doi:10.1021/acs.jmedchem.9b01862. PMID 31850759.
  2. 1 2 3 4 5 6 Cid-Jofré V, Moreno M, Reyes-Parada M, Renard GM (November 2021). "Role of Oxytocin and Vasopressin in Neuropsychiatric Disorders: Therapeutic Potential of Agonists and Antagonists". International Journal of Molecular Sciences. 22 (21) 12077. doi:10.3390/ijms222112077. PMC 8584779. PMID 34769501. On the other hand, OT-12, a potent and long-lasting OT analog has been shown as a powerful OTR agonist with a promising anorexigenic activity. Incorporating fatty acid moieties onto the backbone peptide of OT, results in low in vitro activity with AVP-Rs, improvement in plasma half-life in mice compared to OT and carbetocin, and a significant reduction in body weight in a mouse model of obesity [177].