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
CHEBI:71952
CAS Number
915019-65-7
DrugBank ID
DB11651
TTD ID
D0VG0D

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]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Gene/Protein Processing [5]
Caspase-9 (CASP9) OTD4RFFG CASP9_HUMAN Protein Interaction/Cellular Processes [6]
Cathepsin B (CTSB) OTP9G5QB CATB_HUMAN Protein Interaction/Cellular Processes [6]
Cyclin-dependent kinase inhibitor 1 (CDKN1A) OTQWHCZE CDN1A_HUMAN Gene/Protein Processing [7]
Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1) OTHBQVD5 4EBP1_HUMAN Post-Translational Modifications [5]
G1/S-specific cyclin-D1 (CCND1) OT8HPTKJ CCND1_HUMAN Post-Translational Modifications [7]
Heat shock factor protein 1 (HSF1) OTYNJ4KP HSF1_HUMAN Gene/Protein Processing [8]
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 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.
6 The dual PI3K/mTOR inhibitor NVP-BEZ235 and chloroquine synergize to trigger apoptosis via mitochondrial-lysosomal cross-talk. Int J Cancer. 2013 Jun 1;132(11):2682-93. doi: 10.1002/ijc.27935. Epub 2012 Dec 4.
7 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.
8 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.