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Trelagliptin-13C,d3 is a deuterated labeled Trelagliptin[1]. Trelagliptin (SYR-472) is a potent, orally active and highly selective DPP-4 inhibitor with an IC50 of 4 nM. Trelagliptin succinate improves glycemic control in vivo and can be used for the study of type 2 diabetes mellitus (T2DM)[2]. | [in vivo]
Trelagliptin (oral gavage; 7 mg/kg; single dose) shows sustained PD effect in dogs and gives >80% inhibition of DPP-4 activity even after 24h[2].Trelagliptin (oral gavage; 3 mg/kg; single dose; 60 min prior to oral glucose) significantly improves the glucose tolerance capacity by decreasing the AUC0?120min of 19.3% compared with the vehicle group in ob/ob mice[4].
Trelagliptin (oral gavage; 10 mg/kg; once a week; 8 weeks) caused significant reductions in fasting blood glucose (FBG) levels, and the average reduction during the entire treatment period is 16.8% compared to the control.It also increases insulin level and raised it by 1.7-fold
in AUC0?120min in ob/ob mice[4]. | [References]
[1] Russak EM, et al. Impact of Deuterium Substitution on the Pharmacokinetics of Pharmaceuticals. Ann Pharmacother. 2019 Feb;53(2):211-216. DOI:10.1177/1060028018797110
[2] Bhumika D Patel, et al. Recent approaches to medicinal chemistry and therapeutic potential of dipeptidyl peptidase-4 (DPP-4) inhibitors. Eur J Med Chem. 2014 Mar 3;74:574-605. DOI:10.1016/j.ejmech.2013.12.038
[3] Charles E Grimshaw, et al. Trelagliptin (SYR-472, Zafatek), Novel Once-Weekly Treatment for Type 2 Diabetes, Inhibits Dipeptidyl Peptidase-4 (DPP-4) via a Non-Covalent Mechanism. PLoS One. 2016 Jun 21;11(6):e0157509. DOI:10.1371/journal.pone.0157509
[4] Shiliang Li, et al. Discovery of a Natural-Product-Derived Preclinical Candidate for Once-Weekly Treatment of Type 2 Diabetes. J Med Chem. 2019 Mar 14;62(5):2348-2361. DOI:10.1021/acs.jmedchem.8b01491 |
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