OT-12
| Clinical data | |
|---|---|
| Other names | OT-12; OT12 |
| Routes of administration | Subcutaneous injection[1] |
| Drug class | Oxytocin receptor agonist |
| ATC code |
|
| Identifiers | |
| |
| PubChem CID | |
| Chemical and physical data | |
| Formula | C82H135N15O24S2 |
| Molar mass | 1779.18 g·mol−1 |
| 3D model (JSmol) | |
| |
| |
OT-12 is a long-acting peripherally selective peptide oxytocin receptor agonist.[2][1] 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.[2][1] The drug is highly peripherally selective similarly to oxytocin, with a brain-to-plasma ratio of about 1/190 or 0.5%.[1] However, it shows much greater plasma protein binding and consequent metabolic stability compared to oxytocin.[2][1] 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.[2][1] 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.[1] 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.[2][1] The chemical synthesis of OT-12 has been described.[1] OT-12 was first described in the scientific literature by Elsa Pflimlin and colleagues by 2020.[2][1]
See also
[edit]- Oxytocin receptor agonist
- PF-06655075 (PF1; ASK1476)
References
[edit]- 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.
- 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].