Navitoclax (ABT-263)

Catalog No.S1001 Batch:S100130

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Technical Data

Formula

C47H55ClF3N5O6S3
Molecular Weight 974.61 CAS No. 923564-51-6
Solubility (25°C)* In vitro DMSO 100 mg/mL (102.6 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 A potent inhibitor of Bcl-xL, Bcl-2 and Bcl-w with Ki of ≤ 0.5 nM, ≤1 nM and ≤1 nM in cell-free assays, Navitoclax (ABT-263) binds more weakly to Mcl-1 and A1. Phase 2.
Targets
Bcl-xL [1]
(Cell-free assay)		 Bcl-2 [1]
(Cell-free assay)		 Bcl-w [1]
(Cell-free assay)
<=0.5 nM(Ki) <=1 nM(Ki) <=1 nM(Ki)
In vitro Structurally related to ABT-737, Navitoclax (ABT-263) is a disruptor of Bcl-2/Bcl-xL interactions with pro-apoptotic proteins. Overexpression of the prosurvival Bcl-2 family members is commonly associated with tumor maintenance, progression, and chemoresistance. [1] It displays the protection afforded by overexpression of Bcl-2 or Bcl-xL with EC50 values of 60 nM and 20 nM, respectively. [1] A wide range of cellular activity is observed with this compound having a 50% growth inhibition (EC50) of 110 nM against the most sensitive line (H146), whereas its activity in the least sensitive line (H82) results in an EC50 at 22 μM. All four cell lines with EC50 values of <400 nM (H146, H889, H1963, and H1417) are also highly sensitive to ABT-737, and the two most resistant lines (H1048 and H82) are similarly resistant to ABT-263. [2]
In vivo Navitoclax (ABT-263) demonstrates significant antitumor efficacy when administered at 100 mg/kg/day in the H345 xenograft model, with 80% TGI and 20% of treated tumors indicating at least a 50% reduction in tumor volume. [2] Oral administration of this compound alone causes complete tumor regressions in xenograft models of small-cell lung cancer and acute lymphoblastic leukemia. [2] In xenograft models of aggressive B-cell lymphoma and multiple myeloma where it displays modest or no single agent activity, ABT-263 significantly enhances the efficacy of clinically relevant therapeutic regimens.

Protocol (from reference)

Kinase Assay:

[1]
  • Affinity determination

    Binding affinities (Ki or IC50) of Navitoclax (ABT-263) 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. Bcl-xL (1 nM, His tagged) is mixed with 200 nM f-Bak, 1 nM Tb-labeled anti-His antibody, and this 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

    SCLC cell lines

  • Concentrations

    0-1 μM

  • Incubation Time

    48 hours

  • Method

    Human tumor cell lines SCLC cell lines are maintained at 37℃ containing 5% CO2. SCLC cell lines are cultured in RPMI 1640 with 10% fetal bovine serum (FBS), 1% sodium pyruvate, 25 mM HEPES, 4.5 g/L glucose, and 1% penicillin/streptomycin. Leukemia and lymphoma cell lines are cultured in RPMI 1640 supplemented with 10% FBS and 1% penicillin/streptomycin. Cells (1-5×10 4) are treated by Navitoclax (ABT-263) for 48 hours in 96-well culture plates in a final volume of 100 μL and cytotoxicity is assessed with the CellTiter Glo assay. In vitro cyto toxicity of this compound is assayed.
Animal Study:

[1]
  • Animal Models

    C.B.-17 scid-bg or C.B.-17 scid mice

  • Dosages

    100 mg/kg/d

  • Administration

    Administered via p.o.

References

  • https://pubmed.ncbi.nlm.nih.gov/18451170/
  • https://pubmed.ncbi.nlm.nih.gov/18519752/

Customer Product Validation

Data from [ PLoS One , 2011 , 6, e21980 ]

Data from [ PLoS One , 2011 , 6, e21980 ]

Data from [ PLoS One , 2011 , 6, e21980 ]

<p>Apoptosis induced by BCL2-inhibitors in P-glycoprotein expressing cells. MDCKII wild type or MDR1 cells were exposed to different concentrations of ABT-737 (C) or ABT-263 (D) for 24 h before apoptosis was assessed by flow cytometry using externalization of phosphatidylserine.</p>

Data from [ Biochem Biophys Res Commun , 2011 , 408(2), 344-9 ]

Selleck's Navitoclax (ABT-263) Has Been Cited by 434 Publications

Combination antiretroviral therapy and MCL-1 inhibition mitigate HTLV-1 infection in vivo [ Cell, 2025, S0092-8674(25)00689-0] PubMed: 40645177
First-in-class ultralong-target-residence-time p38α inhibitors as a mitosis-targeted therapy for colorectal cancer [ Nat Cancer, 2025, 6(2):259-277] PubMed: 39820127
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
Integrated omics reveals disease-associated radial glia-like cells with epigenetically dysregulated interferon response in multiple sclerosis [ Neuron, 2025, 113(24):4158-4177.e10] PubMed: 41075785
Secondary Necrosis Following Caspase-Activation can Occur Independently of Gasdermin E [ Adv Sci (Weinh), 2025, 12(46):e07381] PubMed: 41185624
A patient-derived T cell lymphoma biorepository uncovers pathogenetic mechanisms and host-related therapeutic vulnerabilities [ Cell Rep Med, 2025, S2666-3791(25)00102-8] PubMed: 40147445
Development of a robust BH3 drug toolkit for precision medicine in hematologic malignancies [ Theranostics, 2025, 15(12):5705-5718] PubMed: 40365276
S913 phosphorylation of Ulk1 protects the heart from aging through inhibition of cardiac senescence [ Cardiovasc Res, 2025, 121(10):1609-1622] PubMed: 40726430
LP-118 is a novel B-cell lymphoma 2 / extra-large inhibitor that demonstrates efficacy in models of venetoclaxresistant chronic lymphocytic leukemia [ Haematologica, 2025, 110(1):78-91] PubMed: 39113656
A human neuron alzheimer's disease model reveals barriers to senolytic translatability [ Alzheimers Res Ther, 2025, 17(1):176] PubMed: 40713864

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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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