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Details

Stereochemistry ACHIRAL
Molecular Formula C30H23N5O
Molecular Weight 469.5365
Optical Activity UNSPECIFIED
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of DACTOLISIB

SMILES

CN1C(=O)N(C2=C1C=NC3=C2C=C(C=C3)C4=CC5=CC=CC=C5N=C4)C6=CC=C(C=C6)C(C)(C)C#N

InChI

InChIKey=JOGKUKXHTYWRGZ-UHFFFAOYSA-N
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

HIDE SMILES / InChI

Molecular Formula C30H23N5O
Molecular Weight 469.5365
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description

Dactolisib is a dual inhibitor of phosphatidylinositol 3-kinase (P13K) and the downstream mammalian target of rapamycin (mTOR) by binding to the ATP-binding cleft of these enzymes (inhibitor of PI3K/Akt/mTOR cascade). It is being investigated as a possible anti-cancer cancer agent and drug against Influenza virus infections. Frequently reported adverse events included nausea, vomiting, diarrhoea, fatigue/asthenia, anaemia, and anorexia.

Originator

Approval Year

PubMed

PubMed

TitleDatePubMed
Identification and characterization of NVP-BEZ235, a new orally available dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor with potent in vivo antitumor activity.
2008 Jul
Loss of Phosphatase and Tensin homologue deleted on chromosome 10 engages ErbB3 and insulin-like growth factor-I receptor signaling to promote antiestrogen resistance in breast cancer.
2009 May 15
Inhibition profiles of phosphatidylinositol 3-kinase inhibitors against PI3K superfamily and human cancer cell line panel JFCR39.
2010 Apr
Dual targeting of phosphoinositide 3-kinase and mammalian target of rapamycin using NVP-BEZ235 as a novel therapeutic approach in human ovarian carcinoma.
2011 Apr 15
Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies.
2011 Jul
A cell-based screen identifies ATR inhibitors with synthetic lethal properties for cancer-associated mutations.
2011 Jun
Comparison of the effects of the PI3K/mTOR inhibitors NVP-BEZ235 and GSK2126458 on tamoxifen-resistant breast cancer cells.
2011 Jun 1
The dual PI3K/mTOR inhibitor BEZ235 is effective in lung cancer cell lines.
2011 Mar
Modulators of sensitivity and resistance to inhibition of PI3K identified in a pharmacogenomic screen of the NCI-60 human tumor cell line collection.
2012
The synergistic interaction of MEK and PI3K inhibitors is modulated by mTOR inhibition.
2012 Apr 10
Antitumor action of the MET tyrosine kinase inhibitor crizotinib (PF-02341066) in gastric cancer positive for MET amplification.
2012 Jul
Phosphatidylinositol 3-kinase/Akt signaling pathway activates the WNK-OSR1/SPAK-NCC phosphorylation cascade in hyperinsulinemic db/db mice.
2012 Oct
PI3Kδ inhibition augments the efficacy of rapamycin in suppressing proliferation of Epstein-Barr virus (EBV)+ B cell lymphomas.
2013 Aug
Dual inhibitor of phosphoinositide 3-kinase/mammalian target of rapamycin NVP-BEZ235 effectively inhibits cisplatin-resistant urothelial cancer cell growth through autophagic flux.
2013 Jul 18
Preclinical evaluation of the mTOR-PI3K inhibitor BEZ235 in nasopharyngeal cancer models.
2014 Feb 1
Synergistic induction of cell death in haematological malignancies by combined phosphoinositide-3-kinase and BET bromodomain inhibition.
2015 Jul
Patents

Sample Use Guides

In Vivo Use Guide
400 or 300 mg twice daily
Route of Administration: Oral
In Vitro Use Guide
IC50 doses of dactolisib for P3 and U87 glioma cells were established at 12.7 nM and 15.8 nM, respectively.
Substance Class Chemical
Created
by admin
on Mon Oct 21 23:24:09 UTC 2019
Edited
by admin
on Mon Oct 21 23:24:09 UTC 2019
Record UNII
RUJ6Z9Y0DT
Record Status Validated (UNII)
Record Version
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Name Type Language
DACTOLISIB
INN   USAN   WHO-DD  
USAN   INN  
Official Name English
DACTOLISIB [INN]
Common Name English
2-METHYL-2-(4-(3-METHYL-2-OXO-8-(QUINOLIN-3-YL)-2,3-DIHYDROIMIDAZO(4,5-C)QUINOLIN-1-YL)PHENYL)PROPANENITRILE
Systematic Name English
2-METHYL-2-(4-(3-METHYL-2-OXO-8-QUINOLIN-3-YL-2,3-DIHYDRO-1H-IMIDAZO(4,5-C)QUINOLIN-1-YL)PHENYL)PROPANENITRILE
Systematic Name English
BEZ-235
Code English
BEZ235
Code English
DACTOLISIB [USAN]
Common Name English
DACTOLISIB [WHO-DD]
Common Name English
NVP-BEZ-235
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C2152
Created by admin on Mon Oct 21 23:24:09 UTC 2019 , Edited by admin on Mon Oct 21 23:24:09 UTC 2019
NCI_THESAURUS C129825
Created by admin on Mon Oct 21 23:24:09 UTC 2019 , Edited by admin on Mon Oct 21 23:24:09 UTC 2019
Code System Code Type Description
MESH
C531198
Created by admin on Mon Oct 21 23:24:09 UTC 2019 , Edited by admin on Mon Oct 21 23:24:09 UTC 2019
PRIMARY
CAS
915019-65-7
Created by admin on Mon Oct 21 23:24:09 UTC 2019 , Edited by admin on Mon Oct 21 23:24:09 UTC 2019
PRIMARY
PUBCHEM
11977753
Created by admin on Mon Oct 21 23:24:09 UTC 2019 , Edited by admin on Mon Oct 21 23:24:09 UTC 2019
PRIMARY
INN
9545
Created by admin on Mon Oct 21 23:24:09 UTC 2019 , Edited by admin on Mon Oct 21 23:24:09 UTC 2019
PRIMARY
WIKIPEDIA
BEZ235
Created by admin on Mon Oct 21 23:24:09 UTC 2019 , Edited by admin on Mon Oct 21 23:24:09 UTC 2019
PRIMARY
ChEMBL
CHEMBL1879463
Created by admin on Mon Oct 21 23:24:09 UTC 2019 , Edited by admin on Mon Oct 21 23:24:09 UTC 2019
PRIMARY
EPA CompTox
915019-65-7
Created by admin on Mon Oct 21 23:24:09 UTC 2019 , Edited by admin on Mon Oct 21 23:24:09 UTC 2019
PRIMARY
EVMPD
SUB183868
Created by admin on Mon Oct 21 23:24:09 UTC 2019 , Edited by admin on Mon Oct 21 23:24:09 UTC 2019
PRIMARY
NCI_THESAURUS
C74072
Created by admin on Mon Oct 21 23:24:09 UTC 2019 , Edited by admin on Mon Oct 21 23:24:09 UTC 2019
PRIMARY
Related Record Type Details
ACTIVE MOIETY