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ABT-263

Cat. No. M1637
ABT-263 Structure
Synonym:

Navitoclax

Size Price Availability Quantity
10mg USD 80 In stock
50mg USD 200 In stock
100mg USD 350 In stock
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Quality Control
Biological Activity

ABT-263, a novel, orally bioavailable, BH3 mimetic, binds with high affinity (Ki ≤ 1nM) and inhibits multiple antiapoptotic Bcl-2 family proteins. ABT-263 displays activity (EC50 ≤ 1µM) against human lymphoid and small cell lung cancer cell lines. Mechanism based preclinical toxicities include reductions in circulating lymphocytes, apoptosis of circulating platelets, and decreased spermatogenesis, mediated by inhibition of Bcl-2, Bcl-XL and Bcl-w with IC50 values of ≤ 1 nM, ≤0.5 nM and ≤ 1 nM, respectively.

Protocol
Cell Experiment
Cell lines H1048 cells
Preparation method Flourescence Activated Cell Sorting (FACS) for death assays and cell cycle analysis Cells were plated in triplicate in 6-well plates or 6-cm dishes to reach ~30-40% confluency the next day. On the next day, cells were treated with the indicated drugs or no drug control. Apoptosis and cell cycle experiments were performed essentially as previously described and analyzed on a BD LSR III (Becton Dickenson, Franklin Lanes, NJ). The cell cycle experiments were gated to include only viable cells in order for the cell cycle distribution to be determined from this population. For apoptosis assays, the number of cells in quadrants II and IV (Annexin positive) were counted as apoptotic, where cells with subG0/G1 DNA3 were quantified and counted as apoptotic following staining with PI. The Annexin stain was conjugated to FITC and the analysis was done on a Guava easyCyte flow cytometer (EMD Millipore (Temecula, CA)). In the engineered H1048 cells, apoptosis determined by ABT-263 treatment and combination ABT-263/AZD8055 treatment were performed within the same experiment.
Concentrations 500 nM AZD8055, 1 μM ABT-2631
Incubation time 72h
Animal Experiment
Animal models Traditional human cell-line xenograft(6-10 week-old mice with a Nu/Nu background with exponentially growing NCI-H1048 or NCI-H82 cells into the right rear flanks)
Formulation AZD8055 was dissolved in Captisol ®. ABT-263 was dissolved in a mixture of 60% Phosal 50 PG, 30% PEG 400 and 10% EtOH.
Dosages 16 mg/kg/qd AZD8055, 80 mg/kg/qd ABT-263
Administration oral gavage
Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)
Species Mouse Rat Rabbit Guinea pig Hamster Dog
Weight (kg) 0.02 0.15 1.8 0.4 0.08 10
Body Surface Area (m2) 0.007 0.025 0.15 0.05 0.02 0.5
Km factor 3 6 12 8 5 20
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Chemical Information
Molecular Weight 974.61
Formula C47H55ClF3N5O6S3
CAS Number 923564-51-6
Purity 100.00%
Solubility DMSO ≥180 mg/mL
Storage at -20°C
Customer Product Validations & Biological Datas
Source Clin Cancer Res (2017). Figure 4. ABT-263 (Abmole Bioscience)
Method vitro observations
Cell Lines Mice harboring H1975 ER-TWIST+4-OHT tumors
Concentrations 80mg/kg
Incubation Time 5 d
Results The pharmaceutical approach of combining ABT-263 and an EGFRi could be successful in both EGFR mutant lung cancers with EMT-mediated acquired resistance, as well as mesenchymal cancers in the upfront setting.
Rating
Source Proc Natl Acad Sci U S A. (2015). Figure 3. ABT-263 and AZD8055 were purchased from Active Biochemicals (Hong Kong, China) and Abmole Bioscience (Houston, TX)
Method FACS analysis(Apoptosis), Western blotting, Immunoprecipitation (IP),Traditional human cell-line xenograft experiments
Cell Lines SCLC H82 and H1048 cells
Concentrations 500 nM AZD8055, 1 μM ABT-263
Incubation Time 2,16, 72h
Results Combination treatment with ABT-263 and the TORC1/2 inhibitor AZD8055 leads to robust apoptosis and antitumor activity in vivo.
Rating
Source Proc Natl Acad Sci U S A. (2015). Figure 2. ABT-263 and AZD8055 were purchased from Active Biochemicals (Hong Kong, China) and Abmole Bioscience (Houston, TX)
Method FACS analysis(Apoptosis),quantitative (q)RT-PCR, Western blotting, Immunoprecipitation (IP)
Cell Lines SCLC SW1271 and H1048 cells
Concentrations 1µM
Incubation Time 6,48,72h
Results BIM and MCL-1 mediate ABT-263–induced apoptosis in SCLC, and the ratio of BIM to MCL-1 expression predicts the magnitude of apoptosis in SCLC cell lines.
Rating
Source Proc Natl Acad Sci U S A. (2015). Figure 1. ABT-263 and AZD8055 were purchased from Active Biochemicals (Hong Kong, China) and Abmole Bioscience (Houston, TX)
Method quantitative (q)RT-PCR
Cell Lines SCLC cell lines
Concentrations 1µM
Incubation Time 72h
Results we found a modest, but significant, correlation between BIM expression and sensitivity to ABT-263.ABT-263 across both data sets (SI Appendix, Fig. S1 B and C). However, the ratio of BIM to MCL-1 predicted sensitivity to ABT-263 more effectively than the expression of either biomarker alone. SCLC lines have increased BIM expression compared with other solid tumor types along with enhanced sensitivity to ABT-263 compared with other solid tumor types across a large panel of cancer cell lines.
Rating
Product Citations
References

Assessment of ABT-263 activity across a cancer cell line collection leads to a potent combination therapy for small-cell lung cancer.
Faber AC,et.al. Proc Natl Acad Sci U S A. 2015 Mar 17;112(11). PMID: 25737542.

Efficient elimination of cancer cells by deoxyglucose-ABT-263/737 combination therapy.
Yamaguchi et al. PLoS One. 2011;6(9):e24102. PMID: 21949692.

Navitoclax (ABT-263) accelerates apoptosis during drug-induced mitotic arrest by antagonizing Bcl-xL.
Shi et al. Cancer Res. 2011 Jul 1;71(13):4518-26. PMID: 21546570.

Phase I study of Navitoclax (ABT-263), a novel Bcl-2 family inhibitor, in patients with small-cell lung cancer and other solid tumors.
Gandhi et al. J Clin Oncol. 2011 Mar 1;29(7):909-16. PMID: 21282543.

Identification of expression signatures predictive of sensitivity to the Bcl-2 family member inhibitor ABT-263 in small cell lung carcinoma and leukemia/lymphoma cell lines.
Tahir et al. Mol Cancer Ther. 2010 Mar;9(3):545-57. PMID: 20179162.

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  Catalog
Abmole Inhibitor Catalog 2017




Keywords: ABT-263, Navitoclax supplier, Bcl-2, inhibitors

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