venetoclax   Click here for help

GtoPdb Ligand ID: 8318

Synonyms: ABT-199 | GDC-0199 | Venclexta® | Venclyxto®
Approved drug PDB Ligand Immunopharmacology Ligand
venetoclax is an approved drug (FDA and EMA (2016))
Compound class: Synthetic organic
Comment: Venetoclax is a BH3 mimetic that selectively targets Bcl-2 [4], utilised for its pro-apoptotic activity. It is noteworthy that venetoclax is the first approved medicine designed to induce a natural process that helps cells self-destruct.
The IUPAC name provided by PubChem matches 'Example 5' claimed in patent US8580794 [1].
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species

venetoclax is commercially available from our sponsors

2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 9
Hydrogen bond donors 3
Rotatable bonds 14
Topological polar surface area 180.41
Molecular weight 867.32
XLogP 9.38
No. Lipinski's rules broken 2

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES Clc1ccc(cc1)C1=C(CCC(C1)(C)C)CN1CCN(CC1)c1ccc(c(c1)Oc1cnc2c(c1)cc[nH]2)C(=O)NS(=O)(=O)c1ccc(c(c1)[N+](=O)[O-])NCC1CCOCC1
Isomeric SMILES Clc1ccc(cc1)C1=C(CCC(C1)(C)C)CN1CCN(CC1)c1ccc(c(c1)Oc1cnc2c(c1)cc[nH]2)C(=O)NS(=O)(=O)c1ccc(c(c1)[N+](=O)[O-])NCC1CCOCC1
InChI 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)
InChI Key LQBVNQSMGBZMKD-UHFFFAOYSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
No information available.
Summary of Clinical Use Click here for help
Venetoclax (in combination with and in comparison with currently approved anti-neoplastics) was assessed in Phase 3 clinical trials as a potential treatment for chronic lymphocytic leukemia (CLL). See NCT02005471 and NCT02242942 for full details.
In January 2016, the US FDA granted venetoclax (in combination with hypomethylating agents) breakthrough designation as a first-line treatment for patients with acute myeloid leukemia (AML) who are ineligible to receive high-dose chemotherapy.

Full marketing authorisation: In April 2016, the US FDA granted full approval for venetoclax as an oral treatment regimen for patients with chronic lymphocytic leukemia (CLL) with 17p deletion (or TP53 mutation) (detected by an FDA-approved test), who have received at least one prior therapy. EMA approval followed in December 2016. In June 2018, the FDA expanded approval to include treatment of both CLL and small lymphocytic lymphoma (SLL), with or without 17p deletion in patients who have received at least one prior therapy. This approval is for a combined regimen using venetoclax plus the anti-CD20 monoclonal rituximab [3], and offers a chemotherapy-free option for CLL patients. Venetoclax plus anti-CD20 obinutuzumab gained FDA approval for use in adults with CLL or SLL in May 2019, based on results from the CLL14 trial (NCT02242942).
Mechanism Of Action and Pharmacodynamic Effects Click here for help
Venetoclax selectively inhibits the ability of the Bcl-2 protein to sequester its pro-apoptotic family members, thereby restoring the apoptotic balance in cells with aberrant Bcl-2 activity. Venetoclax does not inhibit Bcl-xL, so does not exhibit the anti-platelet side-effect of previously investigated non-selective Bcl-2 inhibitors (eg navitoclax; research code ABT-263).
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT02005471 A Study to Evaluate the Benefit of Venetoclax Plus Rituximab Compared With Bendamustine Plus Rituximab in Participants With Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL) Phase 3 Interventional Hoffmann-La Roche
NCT02242942 A Study to Compare the Efficacy and Safety of Obinutuzumab + Venetoclax (GDC-0199) Versus Obinutuzumab + Chlorambucil in Participants With Chronic Lymphocytic Leukemia Phase 3 Interventional Hoffmann-La Roche
External links Click here for help
For extended ADME data see the following:

Electronic Medicines Compendium (eMC)
Drugs.com
European Medicines Agency (EMA)