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Details

Stereochemistry ACHIRAL
Molecular Formula C45H50ClN7O7S
Molecular Weight 868.439
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of VENETOCLAX

SMILES

CC1(C)CCC(CN2CCN(CC2)C3=CC=C(C(=O)NS(=O)(=O)C4=CC=C(NCC5CCOCC5)C(=C4)[N+]([O-])=O)C(OC6=CN=C7NC=CC7=C6)=C3)=C(C1)C8=CC=C(Cl)C=C8

InChI

InChIKey=LQBVNQSMGBZMKD-UHFFFAOYSA-N
InChI=1S/C45H50ClN7O7S/c1-45(2)15-11-33(39(26-45)31-3-5-34(46)6-4-31)29-51-17-19-52(20-18-51)35-7-9-38(42(24-35)60-36-23-32-12-16-47-43(32)49-28-36)44(54)50-61(57,58)37-8-10-40(41(25-37)53(55)56)48-27-30-13-21-59-22-14-30/h3-10,12,16,23-25,28,30,48H,11,13-15,17-22,26-27,29H2,1-2H3,(H,47,49)(H,50,54)

HIDE SMILES / InChI

Molecular Formula C45H50ClN7O7S
Molecular Weight 868.439
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description

Venetoclax (trade name Venclexta, also known as ABT-199) is a selective and orally bioavailable small-molecule inhibitor of BCL-2, an antiapoptotic protein. BCL-2 and its related proteins BCL-XL and MCL-1 bind to and sequester pro-apoptotic signals in the cell, causing a down-regulation of apoptosis. As an oncogene and an important regulator of apoptosis, BCL-2 overexpression therefore results in increased tumor cell survival and resistance to chemotherapy. FDA approved Venetoclax in April 2016 for the treatment of patients with chronic lymphocytic leukemia (CLL) with 17p deletion, as detected by an FDA approved test, who have received at least one prior therapy. Also this drug in phase 3 clinical trial in combination therapy for the treatment patients with refractory myeloma and Acute Myeloid Leukemia. Common side effects include neutropenia, nausea, anemia, diarrhea, upper respiratory tract infection. Major side effects include tumor lysis syndrome and severe neutropenia.

Originator

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Conditions
PubMed

PubMed

TitleDatePubMed
Bcl-2 gene promotes haemopoietic cell survival and cooperates with c-myc to immortalize pre-B cells.
1988 Sep 29
Potential roles of antisense oligonucleotides in cancer therapy. The example of Bcl-2 antisense oligonucleotides.
2002 Nov
Novel therapies for chronic lymphocytic leukemia.
2004 Jun
An inhibitor of Bcl-2 family proteins induces regression of solid tumours.
2005 Jun 2
Discovery of an orally bioavailable small molecule inhibitor of prosurvival B-cell lymphoma 2 proteins.
2008 Nov 13
The Bcl-xL inhibitor, ABT-737, efficiently induces apoptosis and suppresses growth of hepatoma cells in combination with sorafenib.
2010 Oct
ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets.
2013 Feb
Genomics and drug profiling of fatal TCF3-HLF-positive acute lymphoblastic leukemia identifies recurrent mutation patterns and therapeutic options.
2015 Sep
Patents

Sample Use Guides

In Vivo Use Guide
Initiate therapy with VENCLEXTA (venetoclax) at 20 mg once daily for 7 days, followed by a weekly ramp-up dosing schedule to the recommended daily dose of 400 mg. VENCLEXTA tablets should be taken orally once daily with a meal and water.
Route of Administration: Oral
In Vitro Use Guide
ABT-199 (Venetoclax) shows less sensitivity to Bcl-xL, Mcl-1 and Bcl-w with Ki of 48 nM, > 444 nM and 245 nM, respectively. ABT-199 potently inhibits FL5.12-Bcl-2 cells, RS4;11 cells with EC50 of 4 nM and 8 nM, while shows low activity against FL5. ABT-199 also induces apoptosis in CLL with an average EC50 of 3.0 nM.
Substance Class Chemical
Created
by admin
on Mon Oct 21 20:43:51 UTC 2019
Edited
by admin
on Mon Oct 21 20:43:51 UTC 2019
Record UNII
N54AIC43PW
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
VENETOCLAX
DASH   INN   USAN   WHO-DD  
USAN   INN  
Official Name English
RG7601
Code English
ABT-199
Code English
VENETOCLAX [INN]
Common Name English
VENCLEXTA
Brand Name English
VENETOCLAX [USAN]
Common Name English
4-(4-((2-(4-CHLOROPHENYL)-4,4-DIMETHYLCYCLOHEX-1-EN-1-YL)METHYL)PIPERAZIN-1-YL)-N-((3-NITRO-4-((TETRAHYDRO-2HPYRAN-4-YLMETHYL) AMINO)PHENYL)SULFONYL)-2-(1H-PYRROLO(2,3-B)PYRIDIN-5-YLOXY)BENZAMIDE
Common Name English
RG-7601
Code English
BENZAMIDE, 4-(4-((2-(4-CHLOROPHENYL)-4,4-DIMETHYL-1-CYCLOHEXEN-1-YL)METHYL)-1-PIPERAZINYL)-N-((3-NITRO-4-(((TETRAHYDRO-2H-PYRAN-4-YL)METHYL)AMINO)PHENYL)SULFONYL)-2-(1H-PYRROLO(2,3-B)PYRIDIN-5-YLOXY)-
Common Name English
4-(4-((2-(4-CHLOROPHENYL)-4,4-DIMETHYLCYCLOHEX-1-EN-1-YL)METHYL)PIPERAZIN-1-YL)-N-((3-NITRO-4-((TETRAHYDRO-2H-PYRAN-4-YLMETHYL)AMINO)PHENYL)SULFONYL)-2-(1H-PYRROLO(2,3-B)PYRIDIN-5-YLOXY)BENZAMIDE
Systematic Name English
VENETOCLAX [WHO-DD]
Common Name English
GDC-0199
Code English
Classification Tree Code System Code
FDA ORPHAN DRUG 375612
Created by admin on Mon Oct 21 20:43:51 UTC 2019 , Edited by admin on Mon Oct 21 20:43:51 UTC 2019
NDF-RT N0000192515
Created by admin on Mon Oct 21 20:43:51 UTC 2019 , Edited by admin on Mon Oct 21 20:43:51 UTC 2019
FDA ORPHAN DRUG 536116
Created by admin on Mon Oct 21 20:43:51 UTC 2019 , Edited by admin on Mon Oct 21 20:43:51 UTC 2019
EU-Orphan Drug EU/3/16/1617
Created by admin on Mon Oct 21 20:43:51 UTC 2019 , Edited by admin on Mon Oct 21 20:43:51 UTC 2019
FDA ORPHAN DRUG 664118
Created by admin on Mon Oct 21 20:43:51 UTC 2019 , Edited by admin on Mon Oct 21 20:43:51 UTC 2019
FDA ORPHAN DRUG 423814
Created by admin on Mon Oct 21 20:43:51 UTC 2019 , Edited by admin on Mon Oct 21 20:43:51 UTC 2019
FDA ORPHAN DRUG 506815
Created by admin on Mon Oct 21 20:43:51 UTC 2019 , Edited by admin on Mon Oct 21 20:43:51 UTC 2019
NCI_THESAURUS C129824
Created by admin on Mon Oct 21 20:43:51 UTC 2019 , Edited by admin on Mon Oct 21 20:43:51 UTC 2019
WHO-ATC L01XX52
Created by admin on Mon Oct 21 20:43:51 UTC 2019 , Edited by admin on Mon Oct 21 20:43:51 UTC 2019
FDA ORPHAN DRUG 600117
Created by admin on Mon Oct 21 20:43:51 UTC 2019 , Edited by admin on Mon Oct 21 20:43:51 UTC 2019
Code System Code Type Description
RXCUI
1747556
Created by admin on Mon Oct 21 20:43:51 UTC 2019 , Edited by admin on Mon Oct 21 20:43:51 UTC 2019
PRIMARY
NCI_THESAURUS
C103147
Created by admin on Mon Oct 21 20:43:51 UTC 2019 , Edited by admin on Mon Oct 21 20:43:51 UTC 2019
PRIMARY
EVMPD
SUB176260
Created by admin on Mon Oct 21 20:43:51 UTC 2019 , Edited by admin on Mon Oct 21 20:43:51 UTC 2019
PRIMARY
PUBCHEM
49846579
Created by admin on Mon Oct 21 20:43:51 UTC 2019 , Edited by admin on Mon Oct 21 20:43:51 UTC 2019
PRIMARY
WIKIPEDIA
Venetoclax
Created by admin on Mon Oct 21 20:43:51 UTC 2019 , Edited by admin on Mon Oct 21 20:43:51 UTC 2019
PRIMARY
EPA CompTox
1257044-40-8
Created by admin on Mon Oct 21 20:43:51 UTC 2019 , Edited by admin on Mon Oct 21 20:43:51 UTC 2019
PRIMARY
CAS
1257044-40-8
Created by admin on Mon Oct 21 20:43:51 UTC 2019 , Edited by admin on Mon Oct 21 20:43:51 UTC 2019
PRIMARY
NDF-RT
N0000009176
Created by admin on Mon Oct 21 20:43:51 UTC 2019 , Edited by admin on Mon Oct 21 20:43:51 UTC 2019
PRIMARY Increased Cellular Death [PE]
NDF-RT
N0000185503
Created by admin on Mon Oct 21 20:43:51 UTC 2019 , Edited by admin on Mon Oct 21 20:43:51 UTC 2019
PRIMARY P-Glycoprotein Inhibitors [MoA]
ChEMBL
CHEMBL3137309
Created by admin on Mon Oct 21 20:43:51 UTC 2019 , Edited by admin on Mon Oct 21 20:43:51 UTC 2019
PRIMARY
INN
9925
Created by admin on Mon Oct 21 20:43:51 UTC 2019 , Edited by admin on Mon Oct 21 20:43:51 UTC 2019
PRIMARY
Related Record Type Details
EXCRETED UNCHANGED
AMOUNT EXCRETED
FECAL
TARGET -> INHIBITOR
BINDING
Ki
METABOLIC ENZYME -> SUBSTRATE
TRANSPORTER -> INHIBITOR
IC50
TRANSPORTER -> SUBSTRATE
EFFLUX RATIO
TRANSPORTER -> INHIBITOR
INHIBITOR
IC50
TRANSPORTER -> SUBSTRATE
EFFLUX RATIO
BINDER->LIGAND
BINDING
METABOLIC ENZYME -> SUBSTRATE
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC
Tmax PHARMACOKINETIC ORAL ADMINISTRATION