4JH0

Crystal structure of dipeptidyl-peptidase 4 (CD26, adenosine deaminase complexing protein 2) (DPP-IV-WT) complex with bms-767778 AKA 2-(3-(aminomethyl)-4-(2,4- dichlorophenyl)-2-methyl-5-oxo-5,7-dihydro-6h-pyrrolo[3,4- b]pyridin-6-yl)-n,n-dimethylacetamide

Summary for 4JH0

• Entry DOI: 10.2210/pdb4jh0/pdb
• Descriptor: Dipeptidyl peptidase 4, 2-[3-(aminomethyl)-4-(2,4-dichlorophenyl)-2-methyl-5-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridin-6-yl]-N,N-dimethylacetamide (3 entities in total)
• Functional Keywords: exopeptidase, alpha/beta hydrolase fold, beta barrel, beta propeller, dpp-iv, dimer, hydrolase
• Biological source: Homo sapiens (human)
• Cellular location: Dipeptidyl peptidase 4 soluble form: Secreted. Cell membrane; Single-pass type II membrane protein: P27487
• Total number of polymer chains: 2
• Total formula weight: 169739.82

Authors

Klei, H.E. (deposition date: 2013-03-04, release date: 2013-09-04, Last modification date: 2024-10-09)

Primary citation

Devasthale, P.,Wang, Y.,Wang, W.,Fevig, J.,Feng, J.,Wang, A.,Harrity, T.,Egan, D.,Morgan, N.,Cap, M.,Fura, A.,Klei, H.E.,Kish, K.,Weigelt, C.,Sun, L.,Levesque, P.,Moulin, F.,Li, Y.X.,Zahler, R.,Kirby, M.S.,Hamann, L.G.
Optimization of Activity, Selectivity, and Liability Profiles in 5-Oxopyrrolopyridine DPP4 Inhibitors Leading to Clinical Candidate (Sa)-2-(3-(Aminomethyl)-4-(2,4-dichlorophenyl)-2-methyl-5-oxo-5H-pyrrolo[3,4-b]pyridin-6(7H)-yl)-N,N-dimethylacetamide (BMS-767778).
J.Med.Chem., 56:7343-7357, 2013

PubMed Abstract: Optimization of a 5-oxopyrrolopyridine series based upon structure-activity relationships (SARs) developed from our previous efforts on a number of related bicyclic series yielded compound 2s (BMS-767778) with an overall activity, selectivity, efficacy, PK, and developability profile suitable for progression into the clinic. SAR in the series and characterization of 2s are described.

PubMed: 23964740
DOI: 10.1021/jm4008906

Experimental method

X-RAY DIFFRACTION (2.35 Å)