Venetoclax (ABT-199)

Catalog No.S8048 Batch:S804819

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Technical Data

Formula

C45H50ClN7O7S
Molecular Weight 868.44 CAS No. 1257044-40-8
Solubility (25°C)* In vitro DMSO 100 mg/mL (115.14 mM)
Water Insoluble
Ethanol Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

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.
Targets
Bcl-2 [1]
(Cell-free assay)
<0.01 nM(Ki)
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]
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]
Features Re-engineered version of ABT-263 (Navitoclax).

Protocol (from reference)

Kinase Assay:[1]
  • 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 Assay:[1]
  • 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.
Animal Study:[1]
  • 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

Customer Product Validation

Data from [Data independently produced by Mol Oncol, 2014, 10.1016/j.molonc.2014.09.008]

Data from [J Biol Chem, 2014, 289(23), 16190-9]

Data from [Data independently produced by , , Blood, 2015, 126(11):1346-56]

Data from [Data independently produced by , , Leukemia, 2017, 31(11):2336-2346]

Selleck's Venetoclax (ABT-199) has been cited by 638 publications

RAS-mutant leukaemia stem cells drive clinical resistance to venetoclax [ Nature, 2024, ] PubMed: 39478230
Dual blockade of IL-10 and PD-1 leads to control of SIV viral rebound following analytical treatment interruption [ Nat Immunol, 2024, 10.1038/s41590-024-01952-4] PubMed: 39266691
Proteasome inhibition enhances the anti-leukemic efficacy of chimeric antigen receptor (CAR) expressing NK cells against acute myeloid leukemia [ J Hematol Oncol, 2024, 17(1):85] PubMed: 39285441
Comprehensive characterization of IFNγ signaling in acute myeloid leukemia reveals prognostic and therapeutic strategies [ Nat Commun, 2024, 15(1):1821] PubMed: 38418901
AXL-specific single domain antibodies show diagnostic potential and anti-tumor activity in Acute Myeloid Leukemia [ Theranostics, 2024, 14(7):2656-2674] PubMed: 38773967
AXL-specific single domain antibodies show diagnostic potential and anti-tumor activity in Acute Myeloid Leukemia [ Theranostics, 2024, 14(7):2656-2674] PubMed: 38773967
BH3 mimetics and azacitidine show synergistic effects on juvenile myelomonocytic leukemia [ Leukemia, 2024, 38(1):136-148] PubMed: 37945692
8-Cl-Ado and 8-NH2-Ado synergize with venetoclax to target the methionine-MAT2A-SAM axis in acute myeloid leukemia [ Leukemia, 2024, 10.1038/s41375-024-02222-w] PubMed: 38643304
Targeting BCL2 with Venetoclax Enhances the Efficacy of the KRASG12D Inhibitor MRTX1133 in Pancreatic Cancer [ Cancer Res, 2024, 10.1158/0008-5472.CAN-23-3574] PubMed: 39137400
Dual ON/OFF-switch chimeric antigen receptor controlled by two clinically approved drugs [ Proc Natl Acad Sci U S A, 2024, 121(44):e2405085121] PubMed: 39453747

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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