Venetoclax

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 Search

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	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/208573s000lbl.pdf | https://www.ncbi.nlm.nih.gov/pubmed/28057737 | https://www.ncbi.nlm.nih.gov/pubmed/27698099

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

Primary Target	Pharmacology	Condition	Potency
Apoptosis regulator Bcl-2 19 Target ID: CHEMBL4860 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23291630	Inhibitor 8504

Conditions

Condition	Modality	Highest Phase	Product
Chronic lymphocytic leukemia 59 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/208573s000lbl.pdf	Primary	Approved 8583	VENCLEXTA Approved Use VENCLEXTA is a BCL-2 inhibitor indicated 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. This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. Launch Date 2016
Refractory myeloma 2 Sources: https://www.ncbi.nlm.nih.gov/pubmed/28057737	Primary	Phase III 665	Unknown Approved Use Unknown
Acute myeloid leukemia 141 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27698099	Primary	Phase III 665	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
1.43 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27558232	400 mg 1 times / day multiple, oral dose: 400 mg route of administration: Oral experiment type: MULTIPLE co-administered:		VENETOCLAX plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: HIGH-FAT
2.1 μg/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/208573s000lbl.pdf	400 mg 1 times / day steady-state, oral dose: 400 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		VENETOCLAX plasma	Homo sapiens population: UNKNOWN age: ADULT sex: UNKNOWN food status: LOW-FAT

AUC

Value	Dose	Co-administered	Analyte	Population
30.2 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27558232	400 mg 1 times / day multiple, oral dose: 400 mg route of administration: Oral experiment type: MULTIPLE co-administered:		VENETOCLAX plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: HIGH-FAT
32.8 μg × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/208573s000lbl.pdf	400 mg 1 times / day steady-state, oral dose: 400 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		VENETOCLAX plasma	Homo sapiens population: UNKNOWN age: ADULT sex: UNKNOWN food status: LOW-FAT

T_1/2

Value	Dose	Co-administered	Analyte	Population
14.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27558232	400 mg 1 times / day multiple, oral dose: 400 mg route of administration: Oral experiment type: MULTIPLE co-administered:		VENETOCLAX plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: HIGH-FAT

F_unbound

Value	Dose	Co-administered	Analyte	Population
1% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/208573s000lbl.pdf	400 mg 1 times / day steady-state, oral dose: 400 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		VENETOCLAX plasma	Homo sapiens population: UNKNOWN age: ADULT sex: UNKNOWN food status: LOW-FAT

Doses

Dose	Population	Adverse events
1200 mg 1 times / day steady, oral Highest studied dose Dose: 1200 mg, 1 times / day Route: oral Route: steady Dose: 1200 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/28095146	unhealthy, 66 years (range: 25 - 86 years) Health Status: unhealthy Age Group: 66 years (range: 25 - 86 years) Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/28095146	Disc. AE: Nausea, Diarrhea... Other AEs: Nausea, Diarrhea... AEs leading to discontinuation/dose reduction: Nausea (5 patients) Diarrhea (4 patients) Other AEs: Nausea (grade 1-2, 53%) Diarrhea (grade 1-2, 53%) Diarrhea (grade 3-4, 2%) Fatigue (grade 1-2, 49%) Fatigue (grade 3-4, 6%) Decreased appetite (grade 1-2, 29%) Vomiting (grade 1-2, 24%) Constipation (grade 1-2, 18%) Headache (grade 1-2, 20%) Anemia (grade 1-2, 10%) Anemia (grade 3-4, 8%) Cough (grade 1-2, 10%) Neutropenia (grade 1-2, 12%) Neutropenia (grade 3-4, 8%) Back pain (grade 1-2, 16%) Back pain (grade 3-4, 2%) Upper respiratory tract infection (grade 1-2, 8%) Sources: https://pubmed.ncbi.nlm.nih.gov/28095146
400 mg 1 times / day steady, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: steady Dose: 400 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/208573s000lbl.pdf	unhealthy, 66 years (range: 29 - 85 years) Health Status: unhealthy Age Group: 66 years (range: 29 - 85 years) Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/208573s000lbl.pdf	Disc. AE: Neutropenia, Thrombocytopenia... Other AEs: Neutropenia, Neutrophil count decreased... AEs leading to discontinuation/dose reduction: Neutropenia (grade 3-4, 41%) Thrombocytopenia (grade 3-4, 15%) Febrile neutropenia (serious, 2%) Anemia hemolytic autoimmune (serious, 2%) Other AEs: Neutropenia (all grades, > 20) Neutrophil count decreased (all grades, 45%) Neutrophil count decreased (grade 3-4, 41%) Diarrhea (all grades, > 20) Diarrhea (grade 3-4, <1%) Nausea (grade 3-4, <1%) Nausea (all grades, > 20) Anemia (all grades, > 20) Anemia (grade 3-4, 18%) Hemoglobin decreased (all grades, 29%) Hemoglobin decreased (grade 3-4, 18%) Upper respiratory tract infection (all grades, > 20) Thrombocytopenia (all grades, > 20) Platelet count decreased (all grades, 22%) Platelet count decreased (grade 3-4, 15%) Fatigue (all grades, > 20) Fatigue (grade 3-4, 2%) Pneumonia (serious, 2%) Pyrexia (serious, 2%) Anemia (serious, 2%) Tumor lysis syndrome (serious, 2%) Vomiting (all grades, 15%) Vomiting (grade 3-4, <1%) Constipation (all grades, 14%) Peripheral edema (all grades, 11%) Peripheral edema (grade 3-4, <1%) Upper respiratory tract infection (all grades, 22%) Upper respiratory tract infection (grade 3-4, 1%) Pneumonia (all grades, 8%) Pneumonia (grade 3-4, 5%) Hypokalemia (all grades, 12%) Hypokalemia (grade 3-4, 4%) Back pain (all grades, 10%) Back pain (grade 3-4, <1%) Headache (all grades, 15%) Headache (grade 3-4, <1%) Cough (all grades, 13%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/208573s000lbl.pdf
600 mg 1 times / day steady, oral Dose: 600 mg, 1 times / day Route: oral Route: steady Dose: 600 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/29018077	unhealthy Health Status: unhealthy Sources: https://pubmed.ncbi.nlm.nih.gov/29018077	DLT: Nausea, Abdominal pain... Dose limiting toxicities: Nausea (grade 3, 1 patient) Abdominal pain (grade 2, 1 patient) Vomiting (grade 3, 1 patient) Epigastralgia (grade 3, 1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/29018077

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2252 inducer 1087	inhibitor 2438	inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1741 CYP2C8 1057 CYP1A2 2153 CYP2B6 926 CYP2C19 2057 BCRP 910	CYP3A4/5 91 P-gp 2052 BCRP 697 OATP1B1 503 OATP1B3 435	CYP1A2 832 CYP2B6 669

Drug as perpetrator

Target	Modality	Activity
CYP1A2 2333	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208573Orig1s000ClinPharmR.pdf#page=37 Page: 37.0	no
CYP1A2 2333	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208573Orig1s000ClinPharmR.pdf#page=36 Page: 36.0	no
CYP2B6 1160	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208573Orig1s000ClinPharmR.pdf#page=37 Page: 37.0	no
CYP2B6 1160	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208573Orig1s000ClinPharmR.pdf#page=36 Page: 36.0	no
CYP2C19 2141	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208573Orig1s000ClinPharmR.pdf#page=36 Page: 36.0	no
CYP2D6 2546	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208573Orig1s000ClinPharmR.pdf#page=36 Page: 36.0	no
CYP3A4 2633	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208573Orig1s000ClinPharmR.pdf#page=37 Page: 37.0	no
CYP3A4 2633	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208573Orig1s000ClinPharmR.pdf#page=36 Page: 36.0	no
BCRP 985	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208573Orig1s000ClinPharmR.pdf#page=37 Page: 37.0	yes [IC50 0.13 uM]
CYP2C9 2497	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208573Orig1s000ClinPharmR.pdf#page=36 Page: 36.0	yes [IC50 0.14 uM]
P-gp 1932	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208573Orig1s000ClinPharmR.pdf#page=6 Page: 6.0	yes [IC50 0.79 uM]
CYP2C8 1117	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208573Orig1s000ClinPharmR.pdf#page=36 Page: 36.0	yes [IC50 0.82 uM]

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP3A4/5 91	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208573Orig1s000ClinPharmR.pdf#page=6 Page: 6.0	major	yes (co-administration study) Comment: Co-administration of ketoconazole (a strong CYP3A, P-gp and BCRP inhibitor) increased venetoclax Cmax and AUCX by 2.3- and 6.4-fold, respectively. Co-administration of moderate CYP3A4/5 inhibitors showed a smaller effect on venetoclax exposrue (40 to 60% increase in Cmax and AUCo-24)- Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208573Orig1s000ClinPharmR.pdf#page=6 Page: 6.0
OATP1B1 503	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208573Orig1s000ClinPharmR.pdf#page=32 Page: 32.0	no
OATP1B3 435	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208573Orig1s000ClinPharmR.pdf#page=40 Page: 40.0	no
BCRP 697	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208573Orig1s000ClinPharmR.pdf#page=37 Page: 37.0	yes
P-gp 2052	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208573Orig1s000ClinPharmR.pdf#page=6 Page: 6.0	yes	yes (co-administration study) Comment: Venetoclax exposure also increased (Cmax t 106%, AUCX T 78%) after co-administration of single dose of rifampin, presumably due to the inhibition of P-gp by rifampin. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208573Orig1s000ClinPharmR.pdf#page=6 Page: 6.0

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208573Orig1s000PharmR.pdf#page=43 Page: 43.0

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:133021	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:133021
ChemicalBook	CB62645962	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB62645962
MolPort	MolPort-028-720-431	https://www.molport.com/shop/molecule-link/MolPort-028-720-431
Selleck Chemicals	abt-199	http://www.selleckchem.com/products/abt-199.html
ZINC	ZINC000150338755	http://zinc15.docking.org/substances/ZINC000150338755

PubMed

Title	Date	PubMed
Genomics and drug profiling of fatal TCF3-HLF-positive acute lymphoblastic leukemia identifies recurrent mutation patterns and therapeutic options.	2015-09	26214592
ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets.	2013-02	23291630
The Bcl-xL inhibitor, ABT-737, efficiently induces apoptosis and suppresses growth of hepatoma cells in combination with sorafenib.	2010-10	20799354
Discovery of an orally bioavailable small molecule inhibitor of prosurvival B-cell lymphoma 2 proteins.	2008-11-13	18841882
An inhibitor of Bcl-2 family proteins induces regression of solid tumours.	2005-06-02	15902208
Novel therapies for chronic lymphocytic leukemia.	2004-06	15010151
Potential roles of antisense oligonucleotides in cancer therapy. The example of Bcl-2 antisense oligonucleotides.	2002-11	12445555
Bcl-2 gene promotes haemopoietic cell survival and cooperates with c-myc to immortalize pre-B cells.	1988-09-29	3262202

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 Mar 31 21:27:09 GMT 2025` Edited by `admin` on `Mon Mar 31 21:27:09 GMT 2025`
Record UNII	N54AIC43PW
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

Venetoclax [INN]

Preferred Name

English

Venetoclax

Official Name

English

ABT199

Code

English

RG7601

Code

English

ABT-199

Code

English

Venclexta

Brand Name

English

Venetoclax [ORANGE BOOK]

Common Name

English

Venetoclax [WHO-DD]

Common 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

Systematic Name

English

RG-7601

Code

English

Venetoclax [MI]

Common Name

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)-

Systematic Name

English

Venclyxto

Common Name

English

Venetoclax [JAN]

Common Name

English

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)benzamide

Systematic Name

English

GDC-0199

Code

English

Classification Tree Code System Code

FDA ORPHAN DRUG

375612