 |
PDBsum entry 4jh0
|
|
|
|
PDB id:
|
|
|
|
| Name: |
|
Hydrolase
|
|
|
Title:
|
|
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
|
|
Structure:
|
|
Dipeptidyl peptidase 4. Chain: a, b. Synonym: adabp, adenosine deaminase complexing protein 2, adcp-2, dipeptidyl peptidase iv, dpp iv, t-cell activation antigen cd26, tp103, dipeptidyl peptidase 4 membrane form, dipeptidyl peptidase iv membrane form, dipeptidyl peptidase 4 soluble form, dipeptidyl peptidase iv soluble form. Engineered: yes
|
|
Source:
|
|
Homo sapiens. Human. Organism_taxid: 9606. Gene: dpp4, adcp2, cd26. Expressed in: komagataella pastoris. Expression_system_taxid: 4922.
|
|
Resolution:
|
|
|
2.35Å
|
R-factor:
|
0.244
|
R-free:
|
0.272
|
|
|
Authors:
|
|
H.E.Klei
|
|
Key ref:
|
|
P.Devasthale
et al.
(2013).
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.
PubMed id:
DOI:
|
|
|
Date:
|
|
|
04-Mar-13
|
Release date:
|
04-Sep-13
|
|
|
|
|
|
|
PROCHECK
|
|
|
|
|
|
Headers
|
|
|
|
References
|
|
|
|
|
|
|
|
P27487
(DPP4_HUMAN) -
Dipeptidyl peptidase 4 from Homo sapiens
|
|
|
|
Seq:
Struc:
|
|
|
|
766 a.a.
728 a.a.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Key: |
 |
PfamA domain |
|
|
 |
Secondary structure |
|
 |
CATH domain |
|
|
|
|
|
|
|
|
|
|
|
|
|
Enzyme class:
|
|
E.C.3.4.14.5
- dipeptidyl-peptidase Iv.
|
|
|
|
|
|
|
Reaction:
|
|
Release of an N-terminal dipeptide, Xaa-Xbb-|-Xcc, from a polypeptide, preferentially when Xbb is Pro, provided Xcc is neither Pro nor hydroxyproline.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
| |
|
DOI no:
|
J Med Chem
56:7343-7357
(2013)
|
|
PubMed id:
|
|
|
|
|
|
| |
|
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).
|
|
P.Devasthale,
Y.Wang,
W.Wang,
J.Fevig,
J.Feng,
A.Wang,
T.Harrity,
D.Egan,
N.Morgan,
M.Cap,
A.Fura,
H.E.Klei,
K.Kish,
C.Weigelt,
L.Sun,
P.Levesque,
F.Moulin,
Y.X.Li,
R.Zahler,
M.S.Kirby,
L.G.Hamann.
|
|
|
|
|
| |
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.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
 |
 |
|
Links
