iPPI-DB

Inhibitors of Protein-Protein Interaction Database

Compound 2200

Identifiers

  • Common name: RG7112
  • Canonical SMILES: 
    CCOc1cc(ccc1C1=N[C@@](C)(c2ccc(Cl)cc2)[C@](C)(N1C(=O)N1CCN(CCCS(C)(=O)=O)CC1)c1ccc(Cl)cc1)C(C)(C)C
  • IUPAC name: 
    1-[(4S,5R)-2-(4-tert-butyl-2-ethoxyphenyl)-4,5-bis(4-chlorophenyl)-4,5-dimethyl-4,5-dihydro-1H-imidazole-1-carbonyl]-4-(3-methanesulfonylpropyl)piperazine
  • InChi: 
    InChI=1S/C38H48Cl2N4O4S/c1-8-48-33-26-29(36(2,3)4)14-19-32(33)34-41-37(5,27-10-15-30(39)16-11-27)38(6,28-12-17-31(40)18-13-28)44(34)35(45)43-23-21-42(22-24-43)20-9-25-49(7,46)47/h10-19,26H,8-9,20-25H2,1-7H3/t37-,38+/m0/s1
  • InChiKey: 
    QBGKPEROWUKSBK-QPPIDDCLSA-N

External links


57406853
CHEMBL2386346
1F0
DB14793

External search

Bibliography (2)

Publication Name
Tovar C., Graves B., Packman K., Filipovic Z., Xia B. H. M., Tardell C., Garrido R., Lee E., Kolinsky K., To K.-H., Linn M., Podlaski F., Wovkulich P., Vu B., Vassilev L. T.. . MDM2 Small-Molecule Antagonist RG7112 Activates p53 Signaling and Regresses Human Tumors in Preclinical Cancer Models Cancer Research. RG7112
Vu Binh, Wovkulich Peter, Pizzolato Giacomo, Lovey Allen, Ding Qingjie, Jiang Nan, Liu Jin-Jun, Zhao Chunlin, Glenn Kelli, Wen Yang, Tovar Christian, Packman Kathryn, Vassilev Lyubomir, Graves Bradford. . Discovery of RG7112: A Small-Molecule MDM2 Inhibitor in Clinical Development ACS Medicinal Chemistry Letters. 2g

Pharmacological data

Biochemical tests Cellular tests PK tests Cytotoxicity tests
3 4 1 0

Targets

PPI family Best activity Diseases MMoA
MDM2-Like / P53 7.97 cancer Inhibition
Physicochemical filters
Descriptor Lipinski's RO5 Veber Pfizer's 3/75
Compliance
MW 726.28 g/mol
HBA 8
HBD 0
HBA + HBD 8
AlogP 6.88
TPSA 82.52
RB 10
Radar chart
PCA : iPPI-DB chemical space
PCA : Correlation circle
Efficiencies: iPPI-DB biplot LE versus LLE
Summary
Bibliographic ressources Biochemical tests Cellular tests PK tests Cytotoxicity tests
2 3 4 1 0
Pharmacological data
Bibliography Name Target Competition Assay type Assay name Cell line Activity type Activity
10.1158/0008-5472.CAN-12-2807 RG7112 MDM2
Q00987 		P53
P04637 		Biochemical assay HTRF pIC50 (half maximal inhibitory concentration, -log10) 7.74
10.1158/0008-5472.CAN-12-2807 RG7112 MDM2
Q00987 		P53
P04637 		Biochemical assay HTRF pEC50 (half maximal effective concentration, -log10) 7.97
10.1158/0008-5472.CAN-12-2807 RG7112 MDM2
Q00987 		P53
P04637 		Cellular assay MTT-assay SJSA-1 pEC50 (half maximal effective concentration, -log10) 6.40
10.1021/ml4000657 2g MDM2
Q00987 		P53
P04637 		Cellular assay MTT-assay RKO pIC50 (half maximal inhibitory concentration, -log10) 6.40
10.1021/ml4000657 2g MDM2
Q00987 		P53
P04637 		Cellular assay MTT-assay HCT-116 cells p53WT pIC50 (half maximal inhibitory concentration, -log10) 6.30
10.1021/ml4000657 2g MDM2
Q00987 		P53
P04637 		Cellular assay MTT-assay SJSA-1 pIC50 (half maximal inhibitory concentration, -log10) 6.52
10.1021/ml4000657 2g MDM2
Q00987 		P53
P04637 		Biochemical assay HTRF pIC50 (half maximal inhibitory concentration, -log10) 7.74
PK data
Bibliography Name Assay name Administration mode Dose (mg/kg) Dose interval (hours) Tolerated AUC Clearance Cmax Oral bioavailability T1/2 (min) Tmax (min) Volume distribution (Vd)
10.1021/ml4000657 2g Mouse PK PO PO 50.00 None yes yes no yes None 528 None no
Ta Structure Name Drugbank ID
1.0000 RO-5045337 DB14793
0.8414 Cis-[4,5-Bis-(4-Chlorophenyl)-2-(2-Isopropoxy-4-Methoxyphenyl)-4,5-Dihyd Roimidazol-1-Yl]-Piperazin-1-Yl-Methanone DB04144
0.7500 Cis-[4,5-Bis-(4-Bromophenyl)-2-(2-Ethoxy-4-Methoxyphenyl)-4,5-Dihydroimidazol-1-Yl]-[4-(2-Hydroxyethyl)Piperazin-1-Yl]Methanone DB02872
0.3912 PCO-371 DB14946
0.3721 Copanlisib DB12483
0.3655 Atecegatran metoxil DB12507
0.3626 Timcodar DB12761
0.3587 I-Coeleneterazine DB04146
0.3587 Metralindole DB09306
0.3556 Idanpramine DB13276
0.3546 N-Coeleneterazine DB04118
0.3538 2-[2-ETHANESULFONYLAMINO-3-(5-PROPOXY-1H-INDOL-3-YL)-PROPIONYLAMINO]-PENTANEDIOIC ACID 5-AMIDE 1-(4-CARBAMIMIDOYL-BENZYLAMIDE) DB04606
0.3534 PRI-724 DB15034
0.3504 (6S)-2-amino-6-(3'-methoxybiphenyl-3-yl)-3,6-dimethyl-5,6-dihydropyrimidin-4(3H)-one DB07874
0.3500 Hetacillin DB00739