ABT-199 (Venetoclax)

Catalog No.S8048 Batch:S804817

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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
In Vivo (Add solvents to the product individually and in order.)
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
* <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
(Cell-free assay)
<0.01 nM(Ki)
In vitro Venetoclax (ABT-199) shows less sensitivity to Bcl-xL, Mcl-1 and Bcl-w with Ki of 48 nM, > 444 nM and 245 nM, respectively. It 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. This compound 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 it correlated strongly with the expression of Bcl-2, including NHL, DLBCL, MCL, AML and ALL cell lines. It also induces apoptosis in CLL with an average EC50 of 3.0 nM.
In Vivo Venetoclax (ABT-199) causes a maximal tumour growth inhibition of 95% and tumour growth delay of 152% in RS4;11 xenografts. It also inhibits xenograft growth (DoHH2, Granta-519) as a single agent or in combination with SDX-105 and other agents.
Features Re-engineered version of ABT-263 (Navitoclax).

Protocol (from reference)

Kinase Assay:[1]
  • Binding affinity assays

    Binding affinities (Ki or IC50) of Venetoclax (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). Its binding affinities for Bcl-xL are also determined using a time-resolved fluorescence resonance energy transfer assay. In this assay, Bcl-xL (1 nM, His tagged) is mixed with 200 nM f-Bak, 1 nM Tb-labeled anti-His antibody, and the compound 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 Venetoclax (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 it 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

References

  • https://pubmed.ncbi.nlm.nih.gov/23291630/

Customer Product Validation

THP-1 cells were treated with cytarabine alone and in combination with ABT-199 for 8 h. Whole cell lysates were extracted and subjected to Western blotting, and probed with anti-γH2AX or -β-actin antibody. Densitometry for γH2AX expression was measured, normalized to β-actin, and graphed as fold change compared to the no drug control. The data are presented as mean ± standard error from at least 3 independent Western blots. * indicates p < 0.05.

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

<p>CLL cells were incubated with drugs immediately or co-cultured on CD154 stroma overnight and incubated with the indicated concentrations of ABT-199.</p>

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

(C) OCI-AML2 cells were cultured for 1 day with or without the indicated doses of CB-839 and ABT-199; apoptosis was evaluated based on Annexin V staining. (D) MOLM-14 cells were cultured for 1 day with or without the indicated doses of CB-839 and ABT-199; apoptosis was evaluated based on Annexin-V staining. Histograms show data that are representative of 3 independent experiments. The response of the combination was compared with its single agents against the widely used Loewe model for drug-with-itself dose additivity using Chalice software26 and presented as an isobologram. *P < .05, **P < .01, ***P < .001.

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

(b) MV4-11 cells were treated in vitro with ABT-199 (0.01, 0.1, 1 or 10 μM) with or without BL-8040 (20 μM) for 24 h in 1% FCS RPMI medium. The percentage of dead cells (PI+ cells) was evaluated by FACS. (c) miR-15a and miR-16-1 transfections were performed using Lipofectamine 2000 transfection reagent. At 72 h post-transfection, cells were stained with Annexin-V and PI. FACS plots and numerical data of % cells are shown. The results are expressed as the mean±s.d. and were analyzed using Student’s t-test (*P ⩽0.05 compared with control).

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

Sellecks ABT-199 (Venetoclax) Has Been Cited by 650 Publications

Combination antiretroviral therapy and MCL-1 inhibition mitigate HTLV-1 infection in vivo [ Cell, 2025, S0092-8674(25)00689-0] PubMed: 40645177
Inhibition of heme biosynthesis triggers cuproptosis in acute myeloid leukemia [ Cell, 2025, S0092-8674(25)01233-4] PubMed: 41265435
Anti-BCL2 therapy eliminates giant congenital melanocytic nevus by senolytic and immune induction [ Signal Transduct Target Ther, 2025, 10(1):161] PubMed: 40374605
High mtDNA content identifies oxidative phosphorylation-driven acute myeloid leukemias and represents a therapeutic vulnerability [ Signal Transduct Target Ther, 2025, 10(1):222] PubMed: 40653487
Co-targeting of epigenetic regulators and BCL-XL improves efficacy of immune checkpoint blockade therapy in multiple solid tumors [ Mol Cancer, 2025, 24(1):154] PubMed: 40442785
Tonic type I interferon signaling optimizes the antiviral function of plasmacytoid dendritic cells [ Nat Immunol, 2025, 26(11):1946-1961] PubMed: 41087726
Pathway coessentiality mapping reveals complex II is required for de novo purine biosynthesis in acute myeloid leukaemia [ Nat Metab, 2025, 7(12):2474-2488.] PubMed: 41350470
PIM2 inhibition promotes MCL1 dependency in plasma cells involving integrated stress response-driven NOXA expression [ Nat Commun, 2025, 16(1):256] PubMed: 39747141
CREBBP inactivation sensitizes B cell acute lymphoblastic leukemia to ferroptotic cell death upon BCL2 inhibition [ Nat Commun, 2025, 16(1):4274] PubMed: 40393984
Oncogenic role of RARG rearrangements in acute myeloid leukemia resembling acute promyelocytic leukemia [ Nat Commun, 2025, 16(1):617] PubMed: 39805831

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