Details of the Drug

General Information of Drug (ID: DMKBRDL)

Drug Name
BEZ235
Synonyms BEZ-235; S14-0511; NVP-BEZ-235; NVP-BEZ235, BEZ235; 2-(4-(2,3-dihydro-3-methyl-2-oxo-8-(quinolin-3-yl)imidazo[4,5-c]quinolin-1-yl)phenyl)-2-methylpropanenitrile
Indication
Disease Entry ICD 11 Status REF
Solid tumour/cancer 2A00-2F9Z Phase 2 [1]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 1 Molecular Weight (mw) 469.5
Logarithm of the Partition Coefficient (xlogp) 5.2
Rotatable Bond Count (rotbonds) 3
Hydrogen Bond Donor Count (hbonddonor) 0
Hydrogen Bond Acceptor Count (hbondacc) 4
Chemical Identifiers
Formula
C30H23N5O
IUPAC Name
2-methyl-2-[4-(3-methyl-2-oxo-8-quinolin-3-ylimidazo[4,5-c]quinolin-1-yl)phenyl]propanenitrile
Canonical SMILES
CC(C)(C#N)C1=CC=C(C=C1)N2C3=C4C=C(C=CC4=NC=C3N(C2=O)C)C5=CC6=CC=CC=C6N=C5
InChI
InChI=1S/C30H23N5O/c1-30(2,18-31)22-9-11-23(12-10-22)35-28-24-15-19(21-14-20-6-4-5-7-25(20)32-16-21)8-13-26(24)33-17-27(28)34(3)29(35)36/h4-17H,1-3H3
InChIKey
JOGKUKXHTYWRGZ-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
11977753
ChEBI ID
CHEMBL1879463
CAS Number
915019-65-7
UNII
RUJ6Z9Y0DT
DrugBank ID
DB11651
TTD ID
D0VG0D
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Drug ADMET Endpoint Profile (DAE)NEW Click to Jump to the Detailed DAE Information of This Drug

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
PI3-kinase gamma (PIK3CG) TTHBTOP PK3CG_HUMAN Modulator [2]
Serine/threonine-protein kinase mTOR (mTOR) TTCJG29 MTOR_HUMAN Modulator [2]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
Baculoviral IAP repeat-containing protein 5 (BIRC5) OTILXZYL BIRC5_HUMAN Gene/Protein Processing [3]
Bcl-2-like protein 1 (BCL2L1) OTRC5K9O B2CL1_HUMAN Gene/Protein Processing [4]
Bcl-2-like protein 11 (BCL2L11) OTNQQWFJ B2L11_HUMAN Gene/Protein Processing [4]
Cyclin-dependent kinase inhibitor 1 (CDKN1A) OTQWHCZE CDN1A_HUMAN Gene/Protein Processing [5]
Heat shock factor protein 1 (HSF1) OTYNJ4KP HSF1_HUMAN Gene/Protein Processing [6]
Microtubule-associated proteins 1A/1B light chain 3A (MAP1LC3A) OTPMGIU4 MLP3A_HUMAN Biochemical Pathways [5]
Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN) OTOWDUNT PTEN_HUMAN Drug Response [7]
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA) OTTOMI8J PK3CA_HUMAN Drug Response [8]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Protein Interaction/Cellular Processes [9]
Retinoblastoma-associated protein (RB1) OTQJUJMZ RB_HUMAN Gene/Protein Processing [5]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Solid tumour/cancer
ICD Disease Classification 2A00-2F9Z
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
PI3-kinase gamma (PIK3CG) DTT PIK3CG 1.98E-01 -0.05 -0.55
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

References

1 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7950).
2 The dual PI3K/mTOR inhibitor NVP-BEZ235 is a potent inhibitor of ATM- and DNA-PKCs-mediated DNA damage responses. Neoplasia. 2012 Jan;14(1):34-43.
3 Antitumor action of the MET tyrosine kinase inhibitor crizotinib (PF-02341066) in gastric cancer positive for MET amplification. Mol Cancer Ther. 2012 Jul;11(7):1557-64. doi: 10.1158/1535-7163.MCT-11-0934. Epub 2012 Jun 22.
4 Synergistic induction of cell death in haematological malignancies by combined phosphoinositide-3-kinase and BET bromodomain inhibition. Br J Haematol. 2015 Jul;170(2):275-8. doi: 10.1111/bjh.13283. Epub 2015 Jan 12.
5 Dual inhibitor of phosphoinositide 3-kinase/mammalian target of rapamycin NVP-BEZ235 effectively inhibits cisplatin-resistant urothelial cancer cell growth through autophagic flux. Toxicol Lett. 2013 Jul 18;220(3):267-76. doi: 10.1016/j.toxlet.2013.04.021. Epub 2013 May 4.
6 A Gene Expression Biomarker Predicts Heat Shock Factor 1 Activation in a Gene Expression Compendium. Chem Res Toxicol. 2021 Jul 19;34(7):1721-1737. doi: 10.1021/acs.chemrestox.0c00510. Epub 2021 Jun 25.
7 Dual targeting of phosphoinositide 3-kinase and mammalian target of rapamycin using NVP-BEZ235 as a novel therapeutic approach in human ovarian carcinoma. Clin Cancer Res. 2011 Apr 15;17(8):2373-84. doi: 10.1158/1078-0432.CCR-10-2289. Epub 2011 Mar 3.
8 Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Invest. 2011 Jul;121(7):2750-67. doi: 10.1172/JCI45014.
9 Comparison of the effects of the PI3K/mTOR inhibitors NVP-BEZ235 and GSK2126458 on tamoxifen-resistant breast cancer cells. Cancer Biol Ther. 2011 Jun 1;11(11):938-46. doi: 10.4161/cbt.11.11.15527. Epub 2011 Jun 1.