iPPI-DB

Inhibitors of Protein-Protein Interaction Database

Compound 1292

Identifiers

  • Canonical SMILES: 
    OC(=O)[C@@H](N1[C@@H](c2ccc(Cl)cc2)C(=O)Nc2ccc(I)cc2C1=O)c1ccc(Cl)cc1
  • IUPAC name: 
    (2S)-2-(4-chlorophenyl)-2-[(3S)-3-(4-chlorophenyl)-7-iodo-2,5-dioxo-2,3,4,5-tetrahydro-1H-1,4-benzodiazepin-4-yl]acetic acid
  • InChi: 
    InChI=1S/C23H15Cl2IN2O4/c24-14-5-1-12(2-6-14)19-21(29)27-18-10-9-16(26)11-17(18)22(30)28(19)20(23(31)32)13-3-7-15(25)8-4-13/h1-11,19-20H,(H,27,29)(H,31,32)/t19-,20-/m0/s1
  • InChiKey: 
    HQEQUYKKMMKSSX-PMACEKPBSA-N

External links


656933
CHEMBL361103
571179
DIZ

External search

Bibliography (4)

Publication Name
Parks DJ, Lafrance LV, Calvo RR, Milkiewicz KL, Gupta V, Lattanze J, Ramachandren K, Carver TE, Petrella EC, Cummings MD, Maguire D, Grasberger BL, Lu T. . 1,4-Benzodiazepine-2,5-diones as small molecule antagonists of the HDM2-p53 interaction: discovery and SAR. Bioorganic & medicinal chemistry letters. 20
Grasberger BL, Lu T, Schubert C, Parks DJ, Carver TE, Koblish HK, Cummings MD, LaFrance LV, Milkiewicz KL, Calvo RR, Maguire D, Lattanze J, Franks CF, Zhao S, Ramachandren K, Bylebyl GR, Zhang M, Manthey CL, Petrella EC, Pantoliano MW, Deckman IC, Spurlino JC, Maroney AC, Tomczuk BE, Molloy CJ, Bone RF. . Discovery and cocrystal structure of benzodiazepinedione HDM2 antagonists that activate p53 in cells. Journal of medicinal chemistry. 1
Parks DJ, LaFrance LV, Calvo RR, Milkiewicz KL, Marugán JJ, Raboisson P, Schubert C, Koblish HK, Zhao S, Franks CF, Lattanze J, Carver TE, Cummings MD, Maguire D, Grasberger BL, Maroney AC, Lu T. . Enhanced pharmacokinetic properties of 1,4-benzodiazepine-2,5-dione antagonists of the HDM2-p53 protein-protein interaction through structure-based drug design. Bioorganic & medicinal chemistry letters. 1
Grasberger Bruce L., Lu Tianbao, Schubert Carsten, Parks Daniel J., Carver Theodore E., Koblish Holly K., Cummings Maxwell D., LaFrance Louis V., Milkiewicz Karen L., Calvo Raul R., Maguire Diane, Lattanze Jennifer, Franks Carol F., Zhao Shuyuan, Ramachandren Kannan, Bylebyl Gwendolyn R., Zhang Marie, Manthey Carl L., Petrella Eugene C., Pantoliano Michael W., Deckman Ingrid C., Spurlino John C., Maroney Anna C., Tomczuk Bruce E., Molloy Christopher J., Bone Roger F.. . Discovery and Cocrystal Structure of Benzodiazepinedione HDM2 Antagonists That Activate p53 in Cells Journal of Medicinal Chemistry. 1

Pharmacological data

Biochemical tests Cellular tests PK tests Cytotoxicity tests
5 3 0 0

Targets

PPI family Best activity Diseases MMoA
MDM2-Like / P53 7.10 cancer Inhibition
Physicochemical filters
Descriptor Lipinski's RO5 Veber Pfizer's 3/75
Compliance
MW 579.95 g/mol
HBA 6
HBD 2
HBA + HBD 8
AlogP 6.35
TPSA 89.54
RB 4
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
4 5 3 0 0
Pharmacological data
Bibliography Name Target Competition Assay type Assay name Cell line Activity type Activity
15664854 20 MDM2
Q00987
Biochemical assay Fluorescence Polarization pIC50 (half maximal inhibitory concentration, -log10) 6.38
16600594 1 MDM2
Q00987
Biochemical assay Fluorescence Polarization pIC50 (half maximal inhibitory concentration, -log10) 6.38
15715460 1 MDM2
Q00987
Biochemical assay Fluorescence Polarization pKd (dissociation constant, -log10) 7.10
16600594 1 MDM2
Q00987
Cellular assay Proliferation assay MCF7 mammary carcinoma cells pIC50 (half maximal inhibitory concentration, -log10) 4.42
16600594 1 MDM2
Q00987
Cellular assay Proliferation assay MDA MB321 mammary carcinoma cells pIC50 (half maximal inhibitory concentration, -log10) 3.89
10.1021/jm049137g 1 MDM2
Q00987 		P53
P04637 		Cellular assay Proliferation assay HTB-144 pIC50 (half maximal inhibitory concentration, -log10) 4.52
10.1021/jm049137g 1 MDM2
Q00987 		P53
P04637 		Biochemical assay Fluorescence Polarization pIC50 (half maximal inhibitory concentration, -log10) 6.70
10.1021/jm049137g 1 MDM2
Q00987 		P53
P04637 		Biochemical assay Fluorescence Polarization pKd (dissociation constant, -log10) 7.10
Ta Structure Name Drugbank ID
0.5350 Fominoben DB08968
0.4940 Bentiromide DB00522
0.4822 Oxazolam DB15491
0.4753 [(2S)-4-methyl-3-oxo-2,3,4,5-tetrahydro-1H-1,4-benzodiazepin-2-yl]acetic acid DB08717
0.4746 Ioxaglic acid DB09313
0.4695 [1-(3-CHLORO-2-FORMYL-PHENYLCARBAMOYL)-2-METHYL-PROPYL]-CARBAMIC ACID TERT-BUTYL ESTER DB07956
0.4606 2-{[N-(2-ACETYL-5-CHLORO-4-FLUOROPHENYL)GLYCYL]AMINO}BENZOIC ACID DB07085
0.4575 Evocalcet DB12388
0.4540 ALPHA-(2,6-DICHLOROPHENYL)-ALPHA-(2-ACETYL-5-METHYLANILINO)ACETAMIDE DB07332
0.4510 Cloxazolam DB01553
0.4503 Indoprofen DB08951
0.4471 (1S)-1-(3-chlorophenyl)-2-oxo-2-[(1,3,4-trioxo-1,2,3,4-tetrahydroisoquinolin-5-yl)amino]ethyl acetate DB08498
0.4410 Dibenzepin DB13225
0.4381 RG-4733 DB11870
0.4378 (1S)-2-oxo-1-phenyl-2-[(1,3,4-trioxo-1,2,3,4-tetrahydroisoquinolin-5-yl)amino]ethyl acetate DB08497