Molecular Weight(MW): 974.61
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.
Cited by 37 Publications
13 Customer Reviews
KP cells (A) and A549 cells (B) were treated with increasing doses of ATN-224 alone or with the BCL2 inhibitor ABT-263, and cell death (96 hours) was determined.
J Clin Invest, 2014, 124(1): 117-28 . Navitoclax (ABT-263) purchased from Selleck.
Cell lines are also resistant to dual inhibition of Bcl-xL and Bcl-2 by the inhibitor ABT-263 when dosed with NSC siRNA, but co-dosing ABT-263 with Mcl-1 siRNA decreases compound IC50 similar to that observed with WEHI-539. Representative curves for MDA-MB-157 are shown in f.
Cell Death Differ, 2015, 10.1038/cdd.2015.73. Navitoclax (ABT-263) purchased from Selleck.
ABT-263 has a higher albumin binding affinity than ABT-737. The binding capacity of ABT-737 (solid lines) and ABT-263 (dotted lines) to HSA was investigated using a fluorescence polarization assay. A, to measure binding to site 2 on HSA-IIIA, dansyl sarcosine was used as a probe. In this assay the IC50 was 711 and 37μmol/L for ABT-737 and ABT-263, respectively. B, to measure binding to site 1 on HSA-IIA, dansyl L-glutamate was used as a probe. The IC50 was >1,000 and 145 μmol/L for ABT-737 and ABT-263, respectively.
Clin Cancer Res 2010 16, 4217-4225. Navitoclax (ABT-263) purchased from Selleck.
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.
Biochem Biophys Res Commun 2011 408(2), 344-9. Navitoclax (ABT-263) purchased from Selleck.
(A) In vitro generated Mcl-1-deleted Arf-/- p185+ cells stably expressing the indicated constructs were treated with indicated doses of navitoclax (ABT-263) for 24 hours after which percent viable cells were determined (propidium iodide negative cells were scored as viable). Each point represents the average of three independent experiments and the error bars denote the SEM. p185+ Arf-/- cells serve as a control. (B) Arf -null p185+ cells were treated with navitoclax for 24 hours at indicated doses. Lysates were immunoprecipitated with anti-BIM antibody and immune complexes were resolved and western blotted for MCL-1, BCL-2 (human specific antibody), BCL-XL, BIM, PARP and Actin (loading control). Endogenous BIM serves as the control for equal immunoprecipitation. (E&F) p185+ Arf-/- cells were treated with indicated doses of navitoclax and/or (E) IM or (F) DAS for 24 hours after which percent viable cells was determined. Annexin-V and PI negative cells were scored as viable. IL-7 was added to a final concentration of 20 ng/mL.
Navitoclax (ABT-263) purchased from Selleck.
Human Ph+ cell lines: (A) OP-1 Ph+ B-ALL (B) TOM1 Ph+ B-ALL and (C) BV173 Ph+CML blast crisis cell lines were treated with navitoclax, imatinib (IM) or dasatinib (DAS) at indicated doses for 24 hours after which cell lysates were analyzed for expression of MCL-1, BCL-2, BCL-w, BFL-1 and BCL-XL. For potentiation experiments, the percentage of viable cells was determined by Annexin-V and PI negativity.
Navitoclax (ABT-263) purchased from Selleck.
Purity & Quality Control
Choose Selective Bcl-2 Inhibitors
|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.|
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.  ABT-263 displays the protection afforded by overexpression of Bcl-2 or Bcl-xL with EC50 values of 60 nM and 20 nM, respectively.  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. 
|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.  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. |
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.
|In vitro||DMSO||100 mg/mL (102.6 mM)|
|In vivo||Add solvents individually and in order:
5% DMSO+corn oil
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Clinical Trial Information
|NCT Number||Recruitment||Conditions||Sponsor/Collaborators||Start Date||Phases|
|NCT02520778||Recruiting||EGFR Activating Mutation|Recurrent Non-Small Cell Lung Carcinoma|Stage III Non-Small Cell Lung Cancer|Stage IIIA Non-Small Cell Lung Cancer|Stage IIIB Non-Small Cell Lung Cancer|Stage IV Non-Small Cell Lung Cancer||National Cancer Institute (NCI)||March 2016||Phase 1|
|NCT02591095||Active, not recruiting||Platinum-resistant or Refractory Ovarian Cancer||Centre Francois Baclesse|ARCAGY/ GINECO GROUP|French Cancer Research Hospital Program||January 2016||Phase 2|
|NCT02143401||Recruiting||Recurrent Hepatocellular Carcinoma|Solid Neoplasm|Stage IV Hepatocellular Carcinoma||National Cancer Institute (NCI)||November 2014||Phase 1|
|NCT02079740||Recruiting||Advanced Solid Neoplasm|KRAS Gene Mutation|Metastatic Solid Neoplasm|NRAS Gene Mutation|Recurrent Colorectal Carcinoma|Recurrent Lung Carcinoma|Recurrent Pancreatic Carcinoma|Stage III Colorectal Cancer|Stage III Lung Cancer|Stage III Pancreatic Cancer|Stage IIIA Colorectal Cancer|Stage IIIB Colorectal Cancer|Stage IIIC Colorectal Cancer|Stage IV Colorectal Cancer|Stage IV Lung Cancer|Stage IV Pancreatic Cancer|Stage IVA Colorectal Cancer|Stage IVB Colorectal Cancer||National Cancer Institute (NCI)||March 2014||Phase 1|Phase 2|
|NCT01989585||Recruiting||Metastatic Melanoma|Recurrent Melanoma|Solid Neoplasm|Stage IIIA Skin Melanoma|Stage IIIB Skin Melanoma|Stage IIIC Skin Melanoma|Stage IV Skin Melanoma||National Cancer Institute (NCI)||October 2013||Phase 1|Phase 2|
|NCT01828476||Completed||Prostate Cancer||Rutgers, The State University of New Jersey|Rutgers Cancer Institute of New Jersey|National Cancer Institute (NCI)|AbbVie||June 2013||Phase 2|
Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.
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Frequently Asked Questions
I would like to deliver S1001 via i.p. injection, can you suggest a vehicle solution?
S1001 ABT-263 (Navitoclax) can be dissolved in 5% DMSO+corn oil at 7mg/ml as a clear solution.
Could you tell me if the catalog number S1001 can go through the hemato-encephalic barrier?
According to the paper: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3223694/, ABT-263 can not cross brain-blood barrier.