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IUPAC name
Other names
ABT263; ABT-263
3D model (JSmol)
Molar mass 974.61 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Infobox references

Navitoclax (previously ABT-263) is an experimental orally active anti-cancer drug, which is similar in action to obatoclax, except that unlike obatoclax, it does not have off-target effects.[1][2]

Mechanism of action[edit]

Navitoclax inhibits not only Bcl-2, but also Bcl-XL and Bcl-w proteins.[3] Because navitoclax inhibits Bcl-XL, it reduces platelet lifespan, causing thrombocytopenia, and this makes it dose-limiting.

Effects against senescent cells[edit]

In animal studies, navitoclax was found to be a senolytic agent, inducing apoptosis in senescent, but not non-senescent cells.[4] Oral administration of ABT263 to either sublethally irradiated or normally aged mice reduced senescent cells, including senescent bone marrow hematopoietic stem cells and senescent muscle stem cells. This depletion mitigated total-body irradiation-induced premature aging of the hematopoietic system and rejuvenated the aged hematopoietic stem cells and muscle stem cells in normally aged mice.[5]

Clinical trials[edit]

ABT-263 was in clinical trials in 2009.[6] In January 2017, Navitoclax was evaluated as a combination treatment against solid tumors together with trametinib in a clinical trial sponsored by the National Cancer Institute.[7]


Not directly related to cancer, rather as a therapy for scleroderma, Navitoclax appeared to reduce existing fibrosis though inducing apoptosis of myofibroblasts. Further research is required to elucidate the exact mechanisms and confirm studies.


  1. ^ Gandhi, L.; Camidge, D. R.; de Oliveira, M. R.; Bonomi, P.; Gandara, D.; Khaira, D.; Dive, C. (2011). "Phase I study of Navitoclax (ABT-263), a novel Bcl-2 family inhibitor, in patients with small-cell lung cancer and other solid tumors". Journal of Clinical Oncology. 29 (7): 909–916. doi:10.1200/JCO.2010.31.6208. PMC 4668282Freely accessible. PMID 21282543. 
  2. ^ Leverson, J. D., Phillips, D. C., Mitten, M. J., Boghaert, E. R., Diaz, D., Tahir, S. K., ... & Lowes, K. N. (2015). Exploiting selective BCL-2 family inhibitors to dissect cell survival dependencies and define improved strategies for cancer therapy. Science translational medicine, 7(279), 279ra40-279ra40. doi:10.1126/scitranslmed.aaa4642
  3. ^ The Bcl-2/Bcl-XL/Bcl-w Inhibitor, Navitoclax, Enhances the Activity of Chemotherapeutic Agents In Vitro and In Vivo
  4. ^ Zhu, Y; Tchkonia, T; Fuhrmann-Stroissnigg, H; Dai, HM; Ling, YY; Stout, MB; Pirtskhalava, T; Giorgadze, N; Johnson, KO; Giles, CB; Wren, JD; Niedernhofer, LJ; Robbins, PD; Kirkland, JL (2015). "Identification of a Novel Senolytic Agent, Navitoclax, Targeting the Bcl-2 Family of Anti-Apoptotic Factors". Aging Cell. doi:10.1111/acel.12445. PMID 26711051. 
  5. ^ Chang J, Wang Y, Shao L, Laberge RM, Demaria M, Campisi J, Janakiraman K, Sharpless NE, Ding S, Feng W, Luo Y, Wang X, Aykin-Burns N, Krager K, Ponnappan U, Hauer-Jensen M, Meng A, Zhou D (2015). "Clearance of senescent cells by ABT263 rejuvenates aged hematopoietic stem cells in mice". Nature Medicine. 22: 78–83. doi:10.1038/nm.4010. PMC 4762215Freely accessible. PMID 26657143. Retrieved 2015-12-23. 
  6. ^ Alterations in the Noxa/Mcl-1 axis determine sensitivity of small cell lung cancer to the BH3 mimetic ABT-737. Hauck. 2009
  7. ^ National Cancer Institute (sponsor); Corcoran, Ryan. "Trametinib and Navitoclax in Treating Patients With Advanced or Metastatic Solid Tumors". National Institutes of Health. Retrieved 24 June 2017. Identifier: NCT02079740