ABT-263,923564-51-6,IC-0204116

ABT-263 (Navitoclax) is a inhibitor of Bcl-xL, Bcl-2 and Bcl-w, with Ki ≤0.5 nM, ≤1 nM and ≤1 nM respectively[1].
ABT-263 (Navitoclax) is senolytic in some, but not all types of senescent cells: Navitoclax reduced viability of senescent human umbilical vein epithelial cells (HUVECs), IMR90 human lung fibroblasts, and murine embryonic fibroblasts (MEFs)[2]. Navitoclax (1μM ; 60 hours) accelerates apoptosis mainly by inhibiting Bcl-xL[8].
ABT-263 (Navitoclax)exhibited modest (IC50=3-8 μM) single agent potency in 8 ovarian cancer cell lines. Navitoclax(0.4μM;30h) enhanced the activation of caspase 3/7 induced by carboplatin and/or paclitaxel in Igrov-1 cells [3]. Multiple lymphoid subpopulations isolated from the thymi or BM of vavP-Bcl-2 transgenic mice were markedly more sensitive to ABT-263 (Navitoclax)[4].
ABT-263 (Navitoclax) (100 mg/kg/d;p.o;once daily for 21 days) treated a mouse model inoculated with H345 cells, and significant antitumor efficacy was observed [6]. Navitoclax with venetoclax and chemotherapy was well tolerated and had promising efficacy in patients with relapsed/refractory acute lymphoblastic leukemia or lymphoblastic lymphoma[5]. In 44 xenograft models representing 9 different histologies, ABT-263 (Navitoclax) (100 mg/kg/d;i.g; 21 days)demonstrated limited single agent in vivo activity against the PPTP's(pediatric preclinical testing program)solid tumor panels but showed significant activity against xenografts in the ALL panel [7].