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
* <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.)

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Biological Activity

Description Navitoclax (ABT-263) is 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, but 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 ABT-263 is structurally related to ABT-737; it 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] ABT-263 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 ABT-263 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 When ABT-263 is administered at 100 mg/kg/day in the H345 xenograft model, significant antitumor efficacy is observed with 80% TGI and 20% of treated tumors indicating at least a 50% reduction in tumor volume. [2] Oral administration of ABT-263 alone causes complete tumor regressions in xenograft models of small-cell lung cancer and acute lymphoblastic leukemia. In xenograft models of aggressive B-cell lymphoma and multiple myeloma where ABT-263 displays modest or no single agent activity, it significantly enhances the efficacy of clinically relevant therapeutic regimens. [2]

Protocol (from reference)

Kinase Assay:

[1]
  • Affinity determination

    Binding affinities (Ki or IC50) of 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). 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-263 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 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 ABT-263 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.

Customer Product Validation

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

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

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

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

Selleck's Navitoclax (ABT-263) has been cited by 387 publications

Dual Inhibition of CDK4/6 and XPO1 Induces Senescence With Acquired Vulnerability to CRBN-Based PROTAC Drugs [ Gastroenterology, 2024, S0016-5085(24)00062-3] PubMed: 38262581
Detection of senescence using machine learning algorithms based on nuclear features [ Nat Commun, 2024, 15(1):1041] PubMed: 38310113
Targeting of vulnerabilities of drug-tolerant persisters identified through functional genetics delays tumor relapse [ Cell Rep Med, 2024, 5(3):101471] PubMed: 38508142
Tumor cell senescence-induced macrophage CD73 expression is a critical metabolic immune checkpoint in the aging tumor microenvironment [ Theranostics, 2024, 14(3):1224-1240] PubMed: 38323313
Tryptanthrin targets GSTP1 to induce senescence and increases the susceptibility to apoptosis by senolytics in liver cancer cells [ Redox Biol, 2024, 76:103323] PubMed: 39180983
Bi-directional neuro-immune dysfunction after chronic experimental brain injury [ J Neuroinflammation, 2024, 21(1):83] PubMed: 38581043
Bi-directional neuro-immune dysfunction after chronic experimental brain injury [ J Neuroinflammation, 2024, 21(1):83] PubMed: 38581043
Combined inhibition of class 1-PI3K-alpha and delta isoforms causes senolysis by inducing p21WAF1/CIP1 proteasomal degradation in senescent cells [ Cell Death Dis, 2024, 15(5):373] PubMed: 38811535
Recruitment of BAG2 to DNAJ-PKAc scaffolds promotes cell survival and resistance to drug-induced apoptosis in fibrolamellar carcinoma [ Cell Rep, 2024, 43(2):113678.] PubMed: 38236773
Treatment of advanced atherosclerotic mice with ABT-263 reduced indices of plaque stability and increased mortality [ JCI insight, 2024, 9(2):e173863.] PubMed: none

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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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