Venetoclax (ABT-199)

Synonyms: GDC-0199

Venetoclax (ABT-199, GDC-0199) is a Bcl-2-selective inhibitor with Ki of <0.01 nM in cell-free assays, >4800-fold more selective versus Bcl-xL and Bcl-w, and no activity to Mcl-1. Venetoclax is reported to induce cell growth suppression, apoptosis, cell cycle arrest, and autophagy in triple negative breast cancer MDA-MB-231 cells. Phase 3.

Venetoclax (ABT-199) Chemical Structure

Venetoclax (ABT-199) Chemical Structure

CAS: 1257044-40-8

Selleck's Venetoclax (ABT-199) has been cited by 520 publications

Purity & Quality Control

Batch: Purity: 99.97%
99.97

Products often used together with Venetoclax (ABT-199)

A-1331852


Venetoclax and A-1331852, when used in combination with nilotinib, synergistically reduce cell viability, and enhance apoptosis in blast phase-chronic myeloid leukemia cell lines.


Parry N, et al. Cell Death Discov. 2022 Nov 15;8(1):457.

Azacitidine (5-Azacytidine)


Combining Venetoclax and Azacitidine targets leukemia stem cells and disrupts abnormal energy metabolism in AML patients with poor outcomes.


Pollyea DA, et al.Nat Med. 2018 Dec;24(12):1859-1866.

A-1210477


Venetoclax and A-1210477 increase MCL1 expression and synergistically induce apoptosis in acute myeloid leukemia (AML) cells, MOLM13/MV4-11/SKM1/OCI-AML5.


Fiskus W, et al. Blood Cancer J. 2019 Jan 15;9(2):4.

Navitoclax (ABT-263)


Venetoclax, Navitoclax and chemotherapy show promising efficacy and tolerability in patients with relapsed/refractory acute lymphoblastic leukemia.


Pullarkat VA, et al. Cancer Discov. 2021 Jun;11(6):1440-1453.

S63845


Venetoclax and S63845 significantly delay the time to viral rebound by 4-fold after antiretroviral therapy (ART) cessation in a humanized mouse model of HIV-1 infection.


Arandjelovic P, et al. Cell Rep Med. 2023 Aug 23;101178.

Venetoclax (ABT-199) Related Products

Signaling Pathway

Choose Selective Bcl-2 Inhibitors

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
CS-THL1 Growth Inhibition Assay 20 nM 72 h DMSO Inhibits cell growth assessed by cell viability 25916698
CS-THL1 Apoptotic Assay 25 nM DMSO Induces apoptosis 25916698
DoGKiT Apoptotic Assay 50 nM DMSO Induces apoptosis 25916698
RS4-11 Growth Inhibition Assay 72 h IC50=0.0402 μM 25649768
NALM-6 Growth Inhibition Assay 72 h IC50>3 μM 25649768
SU-DHL-6 Growth Inhibition Assay 0.8 μM Inhibits cell growth assessed by cell viability 25590803
OCI-Ly19 Growth Inhibition Assay 1 μM Inhibits cell growth assessed by cell viability 25590803
SU-DHL-6 Function Assay 0.75 μM 18 h Increases pro-survival protein MCL-1 expression 25590803
KCL22 Function Assay 2 μM 48 h DMSO Increases DNA fragamentation 25333252
LOUCY Growth Inhibition Assay 10 μM 48 h DMSO IC50=0.0139 μM 25301704
ALL-SIL Growth Inhibition Assay 10 μM 48 h DMSO IC50=0.1803 μM 25301704
CUTLL1 Growth Inhibition Assay 10 μM 48 h DMSO IC50=0.3823 μM 25301704
KOPTK1 Growth Inhibition Assay 10 μM 48 h DMSO IC50=0.6432 μM 25301704
DND-41 Growth Inhibition Assay 10 μM 48 h DMSO IC50=1.9695 μM 25301704
PF-382 Growth Inhibition Assay 10 μM 48 h DMSO IC50=2.1824 μM 25301704
KARPAS-45 Growth Inhibition Assay 10 μM 48 h DMSO IC50=3.2225 μM 25301704
PEER Growth Inhibition Assay 10 μM 48 h DMSO IC50=4.6403 μM 25301704
CX-1 Growth Inhibition Assay 100 μM 72 h IC50=6.7 μM 25208882
LS147T Growth Inhibition Assay 100 μM 72 h IC50=29.5 μM 25208882
HL-60 Growth Inhibition Assay 48 h IC50<1 μM 24346116
MOLM-13 Growth Inhibition Assay 48 h IC50<1 μM 24346116
OCI-AML2 Growth Inhibition Assay 48 h IC50<1 μM 24346116
Kasumi-1 Growth Inhibition Assay 48 h IC50<1 μM 24346116
KG-1 Growth Inhibition Assay 48 h IC50<1 μM 24346116
THP-1 Growth Inhibition Assay 48 h IC50<1 μM 24346116
MOLM-14 Growth Inhibition Assay 48 h IC50<1 μM 24346116
MOLM-13 Apoptotic Assay 50 nM 24 h Apoptosis induction 24346116
HSB Growth Inhibition Assay 10 μM 48 h DMSO IC50=4.448 μM 24342948
MOLT4 Growth Inhibition Assay 10 μM 48 h DMSO IC50=4.154 μM 24342948
SKW-3/KE-37 Growth Inhibition Assay 10 μM 48 h DMSO IC50=0.712 μM 24342948
SUPT-11 Growth Inhibition Assay 10 μM 48 h DMSO IC50=4.473 μM 24342948
JURKAT Growth Inhibition Assay 10 μM 48 h DMSO IC50=4.893 μM 24342948
CCRF-CEM Growth Inhibition Assay 10 μM 48 h DMSO IC50=1.360 μM 24342948
LOUCY Apoptotic Assay 2 μM 48 h DMSO Apoptosis induction 24342948
RS4:11 Cytotoxicity assay 29407973
RS4:11 MTS assay 72 h 30278333
RS4:11 MTS assay 28926247
Toledo MTS assay 72 h 30278333
NCI60 SRB assay 48 h 27994761
RS4:11 MTT assay 24 h 29453135
melanoma SRB assay 48 h 27994761
leukemia SRB assay 48 h 27994761
renal cancer SRB assay 48 h 27994761
non-small cell lung cancer SRB assay 48 h 27994761
breast cancer SRB assay 48 h 27994761
colon cancer SRB assay 48 h 27994761
ovarian cancer SRB assay 48 h 27994761
CNS cancer SRB assay 48 h 27994761
prostate cancer SRB assay 48 h 27994761
Remb1 MTT assay 24 h 29453135
Click to View More Cell Line Experimental Data

Biological Activity

Description Venetoclax (ABT-199, GDC-0199) is a Bcl-2-selective inhibitor with Ki of <0.01 nM in cell-free assays, >4800-fold more selective versus Bcl-xL and Bcl-w, and no activity to Mcl-1. Venetoclax is reported to induce cell growth suppression, apoptosis, cell cycle arrest, and autophagy in triple negative breast cancer MDA-MB-231 cells. Phase 3.
Features Re-engineered version of ABT-263 (Navitoclax).
Targets
Bcl-2 [1]
(Cell-free assay)
<0.01 nM(Ki)
In vitro
In vitro 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 potently inhibits FL5.12-Bcl-2 cells, RS4;11 cells with EC50 of 4 nM and 8 nM, while shows low activity against FL5.12-Bcl-xL cells with EC50 of 261 nM. ABT-199 induces a rapid apoptosis in RS4;11 cells with cytochrome c release, caspase activation, the externalization of phosphatidylserine and the accumulation of sub-G0/G1 DNA. Quantitative immunoblotting reveals that sensitivity to ABT-199 correlated strongly with the expression of Bcl-2, including NHL, DLBCL, MCL, AML and ALL cell lines. ABT-199 also induces apoptosis in CLL with an average EC50 of 3.0 nM. [1]
Kinase Assay Binding affinity assays
Binding affinities (Ki or IC50) of ABT-199 against different isoforms of Bcl-2 family are determined with competitive fluorescence polarization assays. The following peptide probe/protein pairs are used: 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). Binding affinities for Bcl-xL are also determined using a time-resolved fluorescence resonance energy transfer assay. Bcl-xL (1 nM, His tagged) is mixed with 200 nM f-Bak, 1 nM Tb-labeled anti-His antibody, and ABT-199 at room temperature for 30 min. Fluorescence is measured on an Envision plate reader using a 340/35 nm excitation filter and 520/525 (f-Bak) and 495/510 nm (Tb-labeled anti-His antibody) emission filters.
Cell Research Cell lines NHL, DLBCL, MCL, AML and ALL cell lines
Concentrations ~1 μM
Incubation Time 48 hours
Method RS4;11 cells are seeded at 5 × 104 per well in 96-well plates and treated with ABT-199 diluted in half-log steps starting at 1 μM-0.05 nM. Leukemia and lymphoma cell lines are seeded at 1.5-2 × 104 cells per well in the appropriate medium and incubated with ABT-199 for 48 h. Effects on proliferation are determined using Cell TiterGlo reagent. EC50 values are determined by nonlinear regression analysis of the concentration-response data.
Experimental Result Images Methods Biomarkers Images PMID
Western blot Mcl-1 / Bcl-xl / Bcl-2 / Bak / NOXA / Bim PARP / Cleaved PARP / Caspase 3 / Cleaved caspase3 / p-S6(Ser236/236) 30663221
Growth inhibition assay Cell death Cell viability 28714472
Immunofluorescence Bcl-2 / Mcl-1 28767232
In Vivo
In vivo 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 also inhibits xenograft growth (DoHH2, Granta-519) as a single agent or in combination with SDX-105 and other agents. [1]
Animal Research Animal Models Female C.B-17 SCID mice (DoHH2 and Granta-519 xenografts) and female C.B-17 SCID-beige mice (RS4;11 and Toledo xenografts)
Dosages ~100 mg/kg
Administration Orally
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT05668026 Not yet recruiting
HIV-1-infection
University of Aarhus|The Peter Doherty Institute for Infection and Immunity|Walter and Eliza Hall Institute of Medical Research|The Alfred|Aarhus University Hospital
March 1 2024 Phase 1|Phase 2
NCT06191263 Not yet recruiting
Acute Myeloid Leukemia
Ryvu Therapeutics SA
January 2024 Phase 2
NCT06014489 Not yet recruiting
AML Adult
Stichting Hemato-Oncologie voor Volwassenen Nederland
December 2023 Phase 2

Chemical Information & Solubility

Molecular Weight 868.44 Formula

C45H50ClN7O7S

CAS No. 1257044-40-8 SDF Download Venetoclax (ABT-199) SDF
Smiles CC1(CCC(=C(C1)C2=CC=C(C=C2)Cl)CN3CCN(CC3)C4=CC(=C(C=C4)C(=O)NS(=O)(=O)C5=CC(=C(C=C5)NCC6CCOCC6)[N+](=O)[O-])OC7=CN=C8C(=C7)C=CN8)C
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 100 mg/mL ( (115.14 mM); Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble


Molecular Weight Calculator

In vivo
Batch:

Add solvents to the product individually and in order.


In vivo Formulation Calculator

Preparing Stock Solutions

Molarity Calculator

Mass Concentration Volume Molecular Weight

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

mg/kg g μL

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

Tel: +1-832-582-8158 Ext:3
If you have any other enquiries, please leave a message.

* Indicates a Required Field

Please enter your name.
Please enter your email. Please enter a valid email address.
Please write something to us.

Frequently Asked Questions

Question 1:
Could you please offer some advice on the half-life of the drug ?

Answer:
According to the reference (https://www.ncbi.nlm.nih.gov/pubmed/24212376), the half-life of ABT-199 in dogs is 12.9 hr.

Tags: buy Venetoclax (ABT-199) | Venetoclax (ABT-199) supplier | purchase Venetoclax (ABT-199) | Venetoclax (ABT-199) cost | Venetoclax (ABT-199) manufacturer | order Venetoclax (ABT-199) | Venetoclax (ABT-199) distributor