4PNZ

Human dipeptidyl peptidase IV/CD26 in complex with the long-acting inhibitor Omarigliptin (MK-3102)

Summary for 4PNZ

• Entry DOI: 10.2210/pdb4pnz/pdb
• Descriptor: Dipeptidyl peptidase 4, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, SODIUM ION, ... (6 entities in total)
• Functional Keywords: alpha/beta, beta-propeller, dimer, diabetes, aminopeptidase, cell membrane, disulfide bond, glycoprotein, secreted, serine protease, signal-anchor, transmembrane, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 173700.79

Authors

Scapin, G.,Yan, Y. (deposition date: 2014-02-22, release date: 2014-04-09, Last modification date: 2024-10-16)

Primary citation

Biftu, T.,Sinha-Roy, R.,Chen, P.,Qian, X.,Feng, D.,Kuethe, J.T.,Scapin, G.,Gao, Y.D.,Yan, Y.,Krueger, D.,Bak, A.,Eiermann, G.,He, J.,Cox, J.,Hicks, J.,Lyons, K.,He, H.,Salituro, G.,Tong, S.,Patel, S.,Doss, G.,Petrov, A.,Wu, J.,Xu, S.S.,Sewall, C.,Zhang, X.,Zhang, B.,Thornberry, N.A.,Weber, A.E.
Omarigliptin (MK-3102): A Novel Long-Acting DPP-4 Inhibitor for Once-Weekly Treatment of Type 2 Diabetes.
J.Med.Chem., 57:3205-3212, 2014

PubMed Abstract: In our effort to discover DPP-4 inhibitors with added benefits over currently commercially available DPP-4 inhibitors, MK-3102 (omarigliptin), was identified as a potent and selective dipeptidyl peptidase 4 (DPP-4) inhibitor with an excellent pharmacokinetic profile amenable for once-weekly human dosing and selected as a clinical development candidate. This manuscript summarizes the mechanism of action, scientific rationale, medicinal chemistry, pharmacokinetic properties, and human efficacy data for omarigliptin, which is currently in phase 3 clinical development.

PubMed: 24660890
DOI: 10.1021/jm401992e

Experimental method

X-RAY DIFFRACTION (1.9 Å)