Structure of PDB 4zyf Chain A Binding Site BS01

Receptor Information
>4zyf Chain A (length=93) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
QIPASEQETLVRPKPLLLKLLKSVGAQKDTYTMKEVLFYLGQYIMTKRLY
DEKQQHIVYCSNDLLGDLFGVPSFSVKEHRKIYTMIYRNLVVV
Ligand information
Ligand ID4T4
InChIInChI=1S/C38H47ClN4O4/c1-25(2)47-35-22-33-28(20-34(35)46-5)21-36(44)43(38(33)27-8-10-29(39)11-9-27)32-16-14-30(15-17-32)41(4)23-26-6-12-31(13-7-26)42-19-18-40(3)37(45)24-42/h8-11,14-17,20,22,25-26,31,38H,6-7,12-13,18-19,21,23-24H2,1-5H3/t26-,31-,38-/m0/s1
InChIKeyCLRSLRWKONPSRQ-IIPSPAQQSA-N
SMILES
SoftwareSMILES
ACDLabs 12.01CN6CCN(C5CCC(CN(c1ccc(cc1)N3C(c2ccc(Cl)cc2)c4c(CC3=O)cc(c(c4)OC(C)C)OC)C)CC5)CC6=O
OpenEye OEToolkits 1.7.6CC(C)Oc1cc2c(cc1OC)CC(=O)N(C2c3ccc(cc3)Cl)c4ccc(cc4)N(C)CC5CCC(CC5)N6CCN(C(=O)C6)C
CACTVS 3.385COc1cc2CC(=O)N([C@@H](c3ccc(Cl)cc3)c2cc1OC(C)C)c4ccc(cc4)N(C)C[C@@H]5CC[C@H](CC5)N6CCN(C)C(=O)C6
OpenEye OEToolkits 1.7.6CC(C)Oc1cc2c(cc1OC)CC(=O)N([C@H]2c3ccc(cc3)Cl)c4ccc(cc4)N(C)CC5CCC(CC5)N6CCN(C(=O)C6)C
CACTVS 3.385COc1cc2CC(=O)N([CH](c3ccc(Cl)cc3)c2cc1OC(C)C)c4ccc(cc4)N(C)C[CH]5CC[CH](CC5)N6CCN(C)C(=O)C6
FormulaC38 H47 Cl N4 O4
Name(S)-1-(4-chlorophenyl)-7-isopropoxy-6-methoxy-2-(4-(methyl(((1r,4S)-4-(4-methyl-3-oxopiperazin-1-yl)cyclohexyl)methyl)amino)phenyl)-1,2-dihydroisoquinolin-3(4H)-one;
NVP-CGM097
ChEMBLCHEMBL3601398
DrugBank
ZINC
PDB chain4zyf Chain A Residue 201 [Download ligand structure] [Download structure with residue number starting from 1] [View ligand structure]
Receptor-Ligand Complex Structure
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PDB4zyf Discovery of a Dihydroisoquinolinone Derivative (NVP-CGM097): A Highly Potent and Selective MDM2 Inhibitor Undergoing Phase 1 Clinical Trials in p53wt Tumors.
Resolution1.8 Å
Binding residue
(original residue number in PDB)		L54 F55 G58 I61 M62 Y67 Q72 F86 V93 Y100
Binding residue
(residue number reindexed from 1)		L37 F38 G41 I44 M45 Y50 Q55 F69 V76 Y83
Annotation score1
Binding affinityMOAD: Kd=2.3nM
PDBbind-CN: -logKd/Ki=8.64,Kd=2.3nM
BindingDB: IC50=0.8nM,Ki=1.3nM,Kd=2.3nM
Enzymatic activity
Enzyme Commision number 2.3.2.27: RING-type E3 ubiquitin transferase.
Gene Ontology
Biological Process
GO:0043066 negative regulation of apoptotic process
GO:0051726 regulation of cell cycle
Cellular Component
GO:0005634 nucleus

View graph for
Biological Process
View graph for
Cellular Component
External links
PDB RCSB:4zyf, PDBe:4zyf, PDBj:4zyf
PDBsum4zyf
PubMed26181851
UniProtQ00987|MDM2_HUMAN E3 ubiquitin-protein ligase Mdm2 (Gene Name=MDM2)

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