Venetoclax (formerly known as ABT-199 or GDC-0199; Venclexta) is a potent, selective and orally bioavailable small molecule inhibitor of the anti-apoptotic protein BCL-2 (B-cell lymphoma-2) with Ki of<0.01 nM. On April 11, 2016, the FDA authorized venetoclax for use in CLL patients who have a 17p deletion (a deletion on the short arm of chromosome 17) and who have received at least one prior therapy. Venetoclax works as a BCL-2 inhibitor by mimicking BH3, which is the native ligand of BCL-2. It prevents the anti-apoptotic BCL-2 protein, causing CLL cells to undergo programmed cell death.
Bcl-2 (Ki = 0.01 nM); Bcl-xL (Ki = 48 nM); Bcl-W (Ki = 245 nM)
ABT-199 shows less sensitivity to Bcl-xL, Mcl-1 and Bcl-w with Ki of 48 nM, > 444 nM and 245 nM, respectively. ABT-199 exhibits weak activity against FL5.12-Bcl-xL cells with an EC50 of 261 nM, but potently inhibits FL5.12-Bcl-2 cells, RS4;11 cells with EC50s of 4 nM and 8 nM. In RS4;11 cells, ABT-199 causes a rapid apoptosis that is accompanied by the release of cytochrome c, activation of caspase, externalization of phosphatidylserine, and accumulation of sub-G0/G1 DNA. According to quantitative immunoblotting, Bcl-2 expression was strongly correlated with ABT-199 sensitivity in cell lines from NHL, DLBCL, MCL, AML, and ALL. The average EC50 for ABT-199 inducing apoptosis in CLL is 3.0 nM. 
ABT-199 (100 mg/kg) causes a maximal tumor growth inhibition of 95% and tumor growth delay of 152% in RS4;11 xenografts. ABT-199 can be used alone or in combination with other drugs, such as SDX-105, to inhibit the growth of xenografts (DoHH2, Granta-519). 
Binding affinities (Ki or IC50) of ABT-199 against different isoforms of Bcl-2 family are determined with competitive fluorescence polarization assays. The peptide probe and protein pairs used are as follows: : f-bad (1 nM) and Bcl-xL (6 nM), f-Bax (1 nM) and Bcl-2 (10 nM), f-Bax (1 nM) and Bcl-w (40 nM), f-Noxa (2 nM) and Mcl-1 (40 nM), and f-Bax (1 nM) and Bcl-2-A1 (15 nM). A time-resolved fluorescence resonance energy transfer assay is also used to determine the binding affinities for Bcl-xL. At room temperature, for 30 minutes, Bcl-xL (1 nM, His tagged), 200 nM f-Bak, 1 nM Tb-labeled anti-His antibody, and ABT-199 are combined.
RS4;11 cells are treated with ABT-199 diluted in half-log steps starting at 1 μM-0.05 nM after being seeded at a density of 5 × 104 per well in 96-well plates. ABT-199 is incubated with leukemia and lymphoma cell lines for 48 hours after they have been seeded at 1.5-2 × 104 cells per well in the appropriate medium. Using the Cell TiterGlo reagent, effects on proliferation are assessed. The concentration-response data are analyzed using nonlinear regression to determine the EC50 values.
Mice: Nonobese diabetic/severe combined immunodeficient γ (NSG) mice are given a 150 µL injection of phosphate-buffered saline containing 5×106 luciferase-labeled LOUCY cells at the age of 6 weeks in the tail vein. The IVIS Lumina II imaging system measures the bioluminescence at regular intervals. After the cells have engrafted and the mice have been randomly split into two groups at 6 weeks (each group contains an equal number of males and females), the treatment is initiated on day 0 of the experiment. Venetoclax (ABT-199) 100 mg/kg body weight or vehicle is administered orally to mice for 4 days in a row. Days 0, 2, and 4 are used to measure the bioluminescene.
C, 62.24; H, 5.80; Cl, 4.08; N, 11.29; O, 12.90; S, 3.69
|Related CAS #||
Yellow solid powder
|HS Tariff Code||
Powder -20°C 3 years
4°C 2 years
In solvent -80°C 6 months
-20°C 1 month
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|Solubility (In Vitro)||
DMSO: ~100 mg/mL (~115.1 mM)
Water: <1 mg/mL(slightly soluble or insoluble)
Ethanol: <1 mg/mL
|Solubility (In Vivo)||
5% DMSO+50% PEG 300+5% Tween 80+ddH2O: 5 mg/mL (Please use freshly prepared in vivo formulations for optimal results.)
|Preparing Stock Solutions||1 mg||5 mg||10 mg|
|1 mM||1.1515 mL||5.7575 mL||11.5149 mL|
|5 mM||0.2303 mL||1.1515 mL||2.3030 mL|
|10 mM||0.1151 mL||0.5757 mL||1.1515 mL|
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
In vivo formula preparation method：take μL DMSO mother liquor，join μL Corn oil，mix well and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
|NCT Number||Recruitment||interventions||Conditions||Sponsor/Collaborators||Start Date||Phases|
|NCT05464836||Not yetrecrulting||Drug: CB-103/Drug:Venetoclax||LeukemiaLymphoblastic]Leukemta||M.D.Anderson Cancer Center||December 30 2022||Phase 2|
|NCT05360160||Recruiting||DrugSNDX-5613DrugVenetoclax]Drug-ASTX727||LeukemiaLymphoblastic]Leukemta||M.D.Anderson Cancer Centerastex PharmaceuticalsIncSyndax Pharmaceutic als inc||December 30 2022||Phase 2|