Chemistry:OT-12
OT-12 is a long-acting peripherally selective peptide oxytocin receptor agonist.[1][2] 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.[1][2] The drug is highly peripherally selective similarly to oxytocin, with a brain-to-plasma ratio of about 1/190 or 0.5%.[2] However, it shows much greater plasma protein binding and consequent metabolic stability compared to oxytocin.[1][2] 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.[1][2] 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.[2] 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.[1][2] The chemical synthesis of OT-12 has been described.[2] OT-12 was first described in the scientific literature by Elsa Pflimlin and colleagues by 2020.[1][2]
See also
- Oxytocin receptor agonist
- PF-06655075 (PF1; ASK1476)
References
- ↑ 1.0 1.1 1.2 1.3 1.4 1.5 "Role of Oxytocin and Vasopressin in Neuropsychiatric Disorders: Therapeutic Potential of Agonists and Antagonists". International Journal of Molecular Sciences 22 (21). November 2021. doi:10.3390/ijms222112077. 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].".
- ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 2.8 "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. January 2020. doi:10.1021/acs.jmedchem.9b01862. PMID 31850759.
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