DACTOLISIB

Details

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

SHOW SMILES / InChI

Structure Search

SMILES

CN1C(=O)N(C2=C1C=NC3=CC=C(C=C23)C4=CN=C5C=CC=CC5=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

Description
Sources: https://newdrugapprovals.org/2015/06/12/bez-235-nvp-bez235-dactolisib/
Curator's Comment: description was created based on several sources, including: http://adisinsight.springer.com/drugs/800026094 https://www.ncbi.nlm.nih.gov/pubmed/18606717

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

Targets

Primary Target	Pharmacology	Potency
Serine/threonine-protein kinase mTOR 35 Target ID: CHEMBL2842 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19671762 \| https://www.ncbi.nlm.nih.gov/pubmed/18606717	Inhibitor 8297	21.0 nM [IC50]
PI3-kinase p110-alpha subunit 41 Target ID: CHEMBL4005 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19671762 \| https://www.ncbi.nlm.nih.gov/pubmed/18606717	Inhibitor 8297	4.0 nM [IC50]
PI3-kinase p110-beta subunit 31 Target ID: CHEMBL3145 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19671762 \| https://www.ncbi.nlm.nih.gov/pubmed/18606717	Inhibitor 8297	76.0 nM [IC50]
PI3-kinase p110-gamma subunit 32 Target ID: CHEMBL3267 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19671762 \| https://www.ncbi.nlm.nih.gov/pubmed/18606717	Inhibitor 8297	7.0 nM [IC50]
PI3-kinase p110-delta subunit 43 Target ID: CHEMBL3130 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19671762 \| https://www.ncbi.nlm.nih.gov/pubmed/18606717	Inhibitor 8297	5.0 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Pancreatic neuroendocrine tumors 8 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26851029	Primary	Phase II 1132	Unknown Approved Use Unknown
Breast cancer 434 Sources: http://adisinsight.springer.com/drugs/800026094 https://newdrugapprovals.org/2015/06/12/bez-235-nvp-bez235-dactolisib/	Primary	Phase II 1132	Unknown Approved Use Unknown
Influenza virus infections 33 Sources: http://adisinsight.springer.com/drugs/800026094	Primary	Phase II 1132	Unknown Approved Use Unknown

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P008TV6	https://www.1pchem.com/search?query=1P008TV6
1PlusChem LLC	1P00GSBM	https://www.1pchem.com/search?query=1P00GSBM
A2B Chem	AH82402	http://a2bchem.com/prod/AH82402
AChemBlock	10290	http://www.achemblock.com/catalogsearch/result/?q=10290
AK Scientific	3486AH	https://aksci.com/item_detail.php?cat=3486AH
AK Scientific	X7430	https://aksci.com/item_detail.php?cat=X7430
AOBIOUS INC	AOB87110	http://aobious.com/aobious/search?search_query=AOB87110
ApexBio Technology	A8246	https://www.apexbt.com/catalogsearch/result/?q=A8246
AstaTech	41099	http://astatechinc.com/CPSResult.php?CRNO=41099
Axon MedChem	1281	https://www.axonmedchem.com/product/1281
BLD Pharm	BD629838	http://www.bldpharm.com/search/Search.html?keyword=BD629838
BOC Sciences	915019-65-7	http://www.bocsci.com/description.asp?cas=915019-65-7
Capot Chemical	16657	https://www.capotchem.com/search.do?q=16657
Cayman Chemical	10565	http://www.caymanchem.com/app/template/Product.vm/catalog/10565
Cayman Chemical	21185	http://www.caymanchem.com/app/template/Product.vm/catalog/21185
Chem Scene	CS-0080	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0080
Chem Scene	CS-0711	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0711
ChemShuttle	104794	https://www.chemshuttle.com/catalogsearch/result/?q=104794
Enamine	EN300-60135	https://www.enaminestore.com/catalog/EN300-60135
Excenen	EX-A404	http://www.excenen.com/searchresultlist.php?id=EX-A404
Exclusive Chemistry	2325	http://www.exchemistry.com/chem-catalog/product-2325.html
KeyOrganics	ES-0038	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=ES-0038
Lab Seeker	SC-50495	http://www.labseeker.com/search.php?keywords=SC-50495&category=0
LabSeeker	SC-50495	http://www.labseeker.com/search.php?keywords=SC-50495&category=0
Matrix Scientific	90884	http://www.matrixscientific.com/090884.html
MedChem Express	HY-15174	https://www.medchemexpress.com/search.html?q=HY-15174&ft=&fa=&fp=
MedChem Express	HY-50673	https://www.medchemexpress.com/search.html?q=HY-50673&ft=&fa=&fp=
MolPort	MolPort-005-737-784	https://www.molport.com/shop/molecule-link/MolPort-005-737-784
MolPort	MolPort-039-139-569	https://www.molport.com/shop/molecule-link/MolPort-039-139-569
MolPort	MolPort-044-561-823	https://www.molport.com/shop/molecule-link/MolPort-044-561-823
Molnova	M16571	https://www.molnova.com/en/serch-list.html?keywords=M16571
MuseChem	R043987	https://www.musechem.com/product/R043987.html
MuseChem	R066919	https://www.musechem.com/product/R066919.html
PI Chemicals	PI-42629	http://www.pipharm.com/catalog_products/PI-42629.html
Princeton BioMolecular Research	PBMR227128	http://www.princetonbio.com/order_online?common_id=PBMR227128
ShangHai Biochempartner	BCP000019	http://www.biochempartner.com/search_BCP000019
ShangHai Biochempartner	BCP00216	http://www.biochempartner.com/search_BCP00216
ShangHai Biochempartner	BCP16240	http://www.biochempartner.com/search_BCP16240
Synthonix	14315	https://synthonix.com/catalogsearch/result/?q=14315
TargetMol	T2235	https://www.targetmol.com/search?keyword=T2235
Tetrahedron	TS59327	http://www.thsci.com/search.do?q=TS59327
Toronto Research Chemicals	N925750	https://www.trc-canada.com/product-detail/?CatNum=N925750
Wonderchem	WD06ZUP	http://www.wonder-chem.com/search.html?text=WD06ZUP
eMolecules	114311714	https://orderbb.emolecules.com/search/#?query=114311714
eMolecules	18867474	https://orderbb.emolecules.com/search/#?query=18867474
eMolecules	44811472	https://orderbb.emolecules.com/search/#?query=44811472
mcule	MCULE-1407851271	https://mcule.com/MCULE-1407851271/
mcule	MCULE-7077128450	https://mcule.com/MCULE-7077128450/

PubMed

Title	Date	PubMed
		252160020
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	18606717
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	19435893
Inhibition profiles of phosphatidylinositol 3-kinase inhibitors against PI3K superfamily and human cancer cell line panel JFCR39.	2010 Apr	20129775
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	21372221
Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies.	2011 Jul	21633166
A cell-based screen identifies ATR inhibitors with synthetic lethal properties for cancer-associated mutations.	2011 Jun	21552262
Comparison of the effects of the PI3K/mTOR inhibitors NVP-BEZ235 and GSK2126458 on tamoxifen-resistant breast cancer cells.	2011 Jun 1	21464613
The dual PI3K/mTOR inhibitor BEZ235 is effective in lung cancer cell lines.	2011 Mar	21498705
Modulators of sensitivity and resistance to inhibition of PI3K identified in a pharmacogenomic screen of the NCI-60 human tumor cell line collection.	2012	23029544
The synergistic interaction of MEK and PI3K inhibitors is modulated by mTOR inhibition.	2012 Apr 10	22415236
Antitumor action of the MET tyrosine kinase inhibitor crizotinib (PF-02341066) in gastric cancer positive for MET amplification.	2012 Jul	22729845
Phosphatidylinositol 3-kinase/Akt signaling pathway activates the WNK-OSR1/SPAK-NCC phosphorylation cascade in hyperinsulinemic db/db mice.	2012 Oct	22949526
PI3Kδ inhibition augments the efficacy of rapamycin in suppressing proliferation of Epstein-Barr virus (EBV)+ B cell lymphomas.	2013 Aug	23841834
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	23651616
Preclinical evaluation of the mTOR-PI3K inhibitor BEZ235 in nasopharyngeal cancer models.	2014 Feb 1	24041865
Synergistic induction of cell death in haematological malignancies by combined phosphoinositide-3-kinase and BET bromodomain inhibition.	2015 Jul	25640480

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.

Name

Type

Language

DACTOLISIB

Official Name

English

RTB101

Code

English

RTB-101

Code

English

NSC-751249

Code

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