- Home
- Signaling Pathways
- Apoptosis
- Bcl-2 Family
- ABT-263 (Navitoclax)
ABT-263 (Navitoclax)
Catalog No.
A3007
Potent Bcl-2 family inhibitor, inhibits Bcl-2, Bcl-xL, and Bcl-w
Featured Products
ABT-263 is an orally sellecitive inhibitor of B-cell leukemia 2 (Bcl-2) family of proteins with potential antineoplastic activity. ABT-263 is a small molecular with the formula of C47H55ClF3N5O6S3 and Molecular Weight of 974. As a Bad-like Bh3 minetic, ABT-263 binds to Bcl-2 family proteins Bcl-2, Bcl-xl and Bcl-w, disrupts the interaction between Bcl-2/Bcl-xl /Bcl-w and pro-apoptotic proteins such as Bim, Bad and Bak, which trigger the caspases-initiated cell death pathway to induce apoptosis.
References:
1. Tse et al., ABT-263: A Potent and Orally Bioavailable Bcl-2 Family Inhibitor. Cancer Res. 2008, 68, 3421-3428.?
2. Shoemaker et al., Activity of the Bcl-2 Family Inhibitor ABT-263 in a Panel of Small Cell Lung Cancer Xenograft Models. Clin. Cancer Res. 2008, 14, 3268-3277
- 1. C Matthias Wilk, Flurin Cathomas, et al. "Circulating senescent myeloid cells drive blood brain barrier breakdown and neurodegeneration." bioRxiv. 2023 Oct 11:2023.10.10.561744. PMID: 37873371
- 2. Sarah K Jachim, Jian Zhong, et al. "BMAL1 modulates senescence programming via AP-1." Aging (Albany NY). 2023 Oct 10;15(19):9984-10009. PMID: 37819791
- 3. Anthonymuthu, Jenson, et al. "Charakterisierung des synergistischen anti-neoplastischen Effekts des BH3-Mimetikums ABT-263 und Vacquinol im Glioblastom" Communities & Collections. 10 Oct 2023.
- 4. Daméhan Tchelougou, Nicolas Malaquin, et al. "Defining melanoma combination therapies that provide senolytic sensitivity in human melanoma cells." bioRxiv. October 02, 2023.
- 5. Iseghohimen, Adesuwa. "Overcoming drug resistance: targeting the BCL-2 family and the long non-coding RNA HCP5 in medulloblastoma and colorectal cancer." University of Salford Manchester, ?Jul 3, 2023.
- 6. Jachim, Sarah Katherine. "Cellular Senescence, Circadian Rhythmicity, and Aging." College of Medicine - Mayo Clinic?ProQuest Dissertation & Theses, ?August 2023.?30640800.
- 7. Vanessa Smer-Barreto, Andrea Quintanilla, et al. "Discovery of senolytics using machine learning." Nat Commun. 2023 Jun 10;14(1):3445. PMID: 37301862
- 8. Alessandra Zonari, Lear E Brace, et al. "Senotherapeutic peptide treatment reduces biological age and senescence burden in human skin models." NPJ Aging. 2023 May 22;9(1):10. PMID: 37217561
- 9. Amani A. Gillette, Rebecca A. DeStefanis, et al. "Inhibition of B-cell lymphoma 2 family proteins alters optical redox ratio, mitochondrial polarization, and cell energetics independent of cell state." J Biomed Opt. 2022 May;27(5):056505. PMID: 35643815
- 10. Anna L. Koessinger, Catherine Cloix, et al. "Increased apoptotic sensitivity of glioblastoma enables therapeutic targeting by BH3-mimetics." Cell Death Differ. 2022 Apr 26. PMID: 35473984
- 11. Magdalena Delgado, Randall R. Rainwater, et al. "Primary acute lymphoblastic leukemia cells are susceptible to microtubule depolymerization in G1 and M phases through distinct cell death pathways." J Biol Chem. 2022 Jun;298(6):101939. PMID: 35436470
- 12. Maria Russo, Carmela Spagnuolo, et al. "Biochemical and Cellular Characterization of New Radio-Resistant Cell Lines Reveals a Role of Natural Flavonoids to Bypass Senescence." Int J Mol Sci. 2021 Dec 28;23(1):301. PMID: 35008725
- 13. Florian J Bock, Egor Sedov, et al. "Apoptotic stress-induced FGF signalling promotes non-cell autonomous resistance to cell death." Nat Commun. 2021 Nov 12;12(1):6572. PMID: 34772930
- 14. Barbara Schroeder, Travis Vander Steen, et al. "Fatty acid synthase (FASN) regulates the mitochondrial priming of cancer cells." Cell Death Dis. 2021 Oct 21;12(11):977. PMID: 34675185
- 15. Sebastian Igelmann, Fre′ de′ ric Lessard, et al. "A hydride transfer complex reprograms NAD metabolism and bypasses senescence." Mol Cell. 2021 Sep 16;81(18):3848-3865.e19. PMID: 34547241
- 16. Gabriele Manzella, Devmini C Moonamale, et al. "A combinatorial drug screen in PDX-derived primary rhabdomyosarcoma cells identifies the NOXA - BCL-XL/MCL-1 balance as target for re-sensitization to first-line therapy in recurrent tumors." Neoplasia. 2021 Sep;23(9):929-938. PMID: 34329950
- 17. Yuzhao Huang, Yuchen He, et al. "Senolytic Peptide FOXO4-DRI Selectively Removes Senescent Cells From in vitro Expanded Human Chondrocytes." Front Bioeng Biotechnol. 2021 Apr 29;9:677576. PMID: 33996787
- 18. Ji-Woon Kim, Joachim Herz, et al. "A key requirement for synaptic Reelin signaling in ketamine-mediated behavioral and synaptic action." Proc Natl Acad Sci U S A. 2021 May 18;118(20):e2103079118. PMID: 33975959
- 19. Hae Rim Jung, Yumi Oh, et al. "CRISPR screens identify a novel combination treatment targeting BCL-X L and WNT signaling for KRAS/BRAF-mutated colorectal cancers." Oncogene. 2021 May;40(18):3287-3302. PMID: 33846570
- 20. Melod Mehdipour, Taha Mehdipour, et al. "Plasma dilution improves cognition and attenuates neuroinflammation in old mice." Geroscience. 2020 Nov 15. PMID: 33191466
- 21. Mariana Boroni, Alessandra Zonari, et al. "Highly accurate skin-specific methylome analysis algorithm as a platform to screen and validate therapeutics for healthy aging." Clinical Epigenetics volume 12, Article number: 105 (2020);13 July 2020. PMID: 32660606
- 22. Nicolas Malaquin, Arthur Vancayseele, et al. "DNA Damage- But Not Enzalutamide-Induced Senescence in Prostate Cancer Promotes Senolytic Bcl-xL Inhibitor Sensitivity." Cells 2020, 9(7), 1593;1 July 2020. PMID: 32630281
- 23. Lee YC, Shi YJ, et al. "GSK3β suppression inhibits MCL1 protein synthesis in human acute myeloid leukemia cells." J Cell Physiol. 2020;10.1002/jcp.29884. PMID: 32572959
- 24. Wang LJ, Liou LR, et al. "Albendazole-Induced SIRT3 Upregulation Protects Human Leukemia K562 Cells from the Cytotoxicity of MCL1 Suppression." Int J Mol Sci. 2020;21(11):3907. PMID: 32486166
- 25. Shahbandi A, Rao SG, et al. "BH3 mimetics selectively eliminate chemotherapy-induced senescent cells and improve response in TP53 wild-type breast cancer." Cell Death Differ. 2020;10.1038/s41418-020-0564-6. PMID: 32457483
- 26. Lee YC, Wang LJ, et al. "Inhibition of EGFR pathway promotes the cytotoxicity of ABT-263 in human leukemia K562 cells by blocking MCL1 upregulation." Biochem Pharmacol. 2020;178:114047. PMID: 32446890
- 27. Parrilla A, Barber M, et al. "Aurora Borealis (Bora), Which Promotes Plk1 Activation by Aurora A, Has an Oncogenic Role in Ovarian Cancer." Cancers (Basel). 2020;12(4):886. PMID: 32268485
- 28. Hee Yeon Kim, Byung Il Lee, et al. "Gossypol Suppresses Growth of Temozolomide-Resistant Glioblastoma Tumor Spheres." Biomolecules 2019, 9(10), 595.
- 29. Villalobos-Ortiz M, Ryan J, et al. "BH3 profiling discriminates on-target small molecule BH3 mimetics from putative mimetics." Cell Death Differ. 2019 Jul 22. PMID: 31332296
- 30. Britt EL, Raman S, et al. "Combination of fenretinide and ABT-263 induces apoptosis through NOXA for head and neck squamous cell carcinoma treatment." PLoS One. 2019 Jul 5;14(7):e0219398. PMID: 31276572
- 31. Santos LC, Vogel R, et al. "Mitochondrial origins of fractional control in regulated cell death." Nat Commun. 2019 Mar 21;10(1):1313. PMID: 30899020
- 32. Joe T Sharick, Christine M Walsh, et al. "Optical Metabolic Imaging of Heterogeneous Drug Response in Pancreatic Cancer Patient Organoids." bioRxiv. 2019 February 06.
- 33. Wu S, Fatkhutdinov N, et al. "SWI/SNF catalytic subunits' switch drives resistance to EZH2 inhibitors in ARID1A-mutated cells." Nat Commun. 2018 Oct 8;9(1):4116. PMID: 30297712
- 34. Bera R, Chiu MC, et al. "Genetic and Epigenetic Perturbations by DNMT3A-R882 Mutants Impaired Apoptosis through Augmentation of PRDX2 in Myeloid Leukemia Cells." Neoplasia. 2018 Nov;20(11):1106-1120. PMID: 30245403
- 35. Roscoe I, Parker M, et al. "Human Serum Albumin and the p53-Derived Peptide Fusion Protein Promotes Cytotoxicity Irrespective of p53 Status in Cancer Cells." Mol Pharm. 2018 Oct 10. PMID: 30226785
- 36. Delgado M, Chambers TC. "Microtubules play an essential role in the survival of primary acute lymphoblastic leukemia cells advancing through G1 phase." Cell Cycle. 2018;17(14):1784-1796. PMID: 29995568
- 37. Lee YC, Wang LJ, et al. "ABT-263-induced MCL1 upregulation depends on autophagy-mediated 4EBP1 downregulation in human leukemia cells." Cancer Lett. 2018 Jun 15;432:191-204. PMID: 29913235
- 38. Cao Y, Chen M, et al. "The proton pump inhibitor pantoprazole disrupts protein degradation systems and sensitizes cancer cells to death under various stresses."Cell Death Dis. 2018 May 22;9(6):604. PMID: 29789637
- 39. Giampazolias E, Zunino B, et al. "Mitochondrial permeabilization engages NF-κB-dependent anti-tumour activity under caspase deficiency." Nat Cell Biol. 2017 Sep;19(9):1116-1129. PMID: 28846096
- 40. Russo M, Milito A, et al. "CK2 and PI3K are direct molecular targets of quercetin in chronic lymphocytic leukaemia." Oncotarget. 2017 Jun 27;8(26):42571-42587. PMID: 28489572
- 41. Luis C Santos, Robert Vogel, et al. "Origins of fractional control in regulated cell death" bioRxiv.Oct. 10, 2017.
- 42. Jubierre Zapater, Luz. "Epigenetic regulators in neuroblastoma: BRG1, a future therapeutic target." tdx.cat.2017-10-09.
- 43. Panayotopoulou EG, Müller AK, et al. "Targeting of apoptotic pathways by SMAC or BH3 mimetics distinctly sensitizes paclitaxel-resistant triple negative breast cancer cells."Oncotarget. 2017 Jul 11;8(28):45088-45104. PMID: 28187446
- 44. Olson OC, Kim H, et al. "Tumor-Associated Macrophages Suppress the Cytotoxic Activity of Antimitotic Agents." Cell Rep. 2017 Apr 4;19(1):101-113. PMID: 28380350
- 45. Jubierre, L., et al. "BRG1/SMARCA4 is essential for neuroblastoma cell viability through modulation of cell death and survival pathways." Oncogene (2016). PMID: 26996667
| Storage | Desiccate at -20°C |
| M.Wt | 974.61 |
| Cas No. | 923564-51-6 |
| Formula | C47H55ClF3N5O6S3 |
| Synonyms | Navitoclax,ABT-263,ABT263,ABT 263 |
| Solubility | ≥48.73 mg/mL in DMSO; insoluble in EtOH; insoluble in H2O |
| Chemical Name | (R)-4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((4-morpholino-1-(phenylthio)butan-2-yl)amino)-3-((trifluoromethyl)sulfonyl)phenyl)sulfonyl)benzamide |
| SDF | Download SDF |
| Canonical SMILES | CC(CC1)(C)CC(CN2CCN(C3=CC=C(C(NS(C4=CC=C(N[C@@H](CSC5=CC=CC=C5)CCN6CCOCC6)C(S(C(F)(F)F)(=O)=O)=C4)(=O)=O)=O)C=C3)CC2)=C1C7=CC=C(Cl)C=C7 |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment:[1] | |
|
Cell lines |
Murine DO11.10 T-hybridoma cells expressing murine Bcl-2, Bcl-xL and Bcl-w proteins |
|
Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months. |
|
Reaction Conditions |
None specifc suggestion |
|
Applications |
ABT-263 is an antitumor effector in preclinical and early clinical studies. It binds to Bcl-2, Bcl-xL, and Bcl-w in vitro, but only targets Bcl-2 in vivo. In human non-Hodgkin lymphomas, high expression of Bcl-2 sensitized to ABT-263 elevated proapoptotic Bim. |
| Animal experiment:[2] | |
|
Animal models |
Immune-deficient NOD/SCID or NOD/SCID, ILγ receptor negative mice |
|
Dosage form |
Orally taken at 100 mg/kg/day for 21 days |
|
Applications |
ABT-263 can largely inhibited the activity of patient-derived pediatric acute lymphoblastic leukemia xenograft. ABT-263 sensitivity was correlated with low MCL1 mRNA expression levels. BH3 profiling revealed that resistance to ABT-263 correlated with mitochondrial priming by NOXA peptide. |
|
Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
|
References: 1. Mérino D1, Khaw SL, Glaser SP et al. Bcl-2, Bcl-x(L), and Bcl-w are not equivalent targets of ABT-737 and navitoclax (ABT-263) in lymphoid and leukemic cells.Blood. 2012 Jun 14;119(24):5807-16. 2. Suryani S, Carol H, Chonghaile TN et al. Cell and Molecular Determinants of In Vivo Efficacy of the BH3 Mimetic ABT-263 against Pediatric Acute Lymphoblastic Leukemia Xenografts. Clin Cancer Res. 2014 Jul 10. |
|
| ABT-263 (Navitoclax) is a potent inhibitor of Bcl-xL, Bcl-2 and Bcl-w with Ki of ≤ 0.5 nM, ≤1 nM and ≤1 nM. | ||||||
| Targets | Bcl-xL | Bcl-2 | Bcl-w | |||
| IC50 | ≤ 0.5 nM (Ki) | ≤1 nM (Ki) | ≤ 1 nM (Ki) | |||
Quality Control & MSDS
- View current batch:
Chemical structure
Related Biological Data
Related Biological Data
Related Biological Data
Related Biological Data
Related Biological Data
Related Biological Data
Related Biological Data
