venetoclax   

GtoPdb Ligand ID: 8318

Synonyms: ABT-199 | GDC-0199 | Venclexta® | Venclyxto®
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].
2D Structure
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Physico-chemical Properties
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
SMILES / InChI / InChIKey
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
Bioactivity Comments
Venetoclax is reported to be >4800-fold more selective for Bcl-2 compared to other protein family members Bcl-xL and Bcl-w [4].
Selectivity at other protein targets
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
BCL2 apoptosis regulator Hs Antagonist Antagonist >11.0 pKi - 1,4
pKi >11.0 (Ki <1x10-11 M) [1,4]
Description: Note that this Ki is below the detection limit of the assay.
Bcl-2-like 1 Hs Antagonist Antagonist 7.3 pKi - 4
pKi 7.3 (Ki 4.8x10-8 M) [4]
Bcl-2-like 2 Hs Antagonist Antagonist 6.6 pKi - 4
pKi 6.6 (Ki 2.45x10-7 M) [4]
MCL1 apoptosis regulator, BCL2 family member Hs Antagonist Antagonist <6.3 pKi - 4
pKi <6.3 (Ki >4.44x10-7 M) [4]