SB-T-101141

SB-T-101141 is a novel taxane. SB-T-101141 effectively induces a noncanonical ferroptosis to overcome Paclitaxel (HY-B0015) resistance of breast cancer. SB-T-101141 facilitates the production of iron and ferrous ions and ROS. SB-T-101141 stably binds to KHSRP to inhibit the iron-dependent expression of CISD1 related to iron homeostasis. SB-T-101141 synergistically enhances the iron-dependent activation of JNK and PERK pathways via KHSRP. SB-T-101141 suppresses breast tumor growth in MCF-7(PR)/MDA-MB-231(PR) or KHSRP knock-down MCF-7 xenograft mice model^[1]. In Vitro:SB-T-101141 (1-3 μM, 12 h) efficiently induces microtubule polymerization and tubulin protein expression in MCF-7 and MDA-MB-453 cells^[1].
SB-T-101141 (1-3 μM, 72 h) has potent cytotoxicity with IC₅₀ of 0.03, 0.8 and 6.5 μM for MCF-7, MDA-MB-453 and MDA-MB-231 cells, respectively, while similar effect on normal MCF-10A cells^[1].
SB-T-101141 (0.001-8 μM, 1-14 days) strongly inhibits cell proliferation and colony formation, and increased cell death in MCF-7 and MDA-MB-453 cells^[1].
SB-T-101141 (9 μM, 5 days) effectively inhibits the growth of patient breast cancer organoids^[1].
SB-T-101141 (1-8 μM, 12-60 h) significantly induces cell apoptosis and G2/M phase arrest at 1 μM (no efficacy at high dose), without level changes of cleavages of PARP and caspase-7 in MCF-7 and MDA-MB-453 cells^[1].
SB-T-101141 (3-16 μM, 4-72 h) induces a ferroptosis-like cell death morphology with a low accumulation and increase of membrane permeability, and this effect is markedly blocked by Z-VAD-FMK and Necrostatin-1, with a mild effect on mitochondria numbers and ATP level in MCF-7 and MDA-MB-453 cells^[1].
SB-T-101141 (0.17-8 μM, 0-48 h) significantly increases intracellular iron and ferrous ion as well as MDA level, and reduces GSH level without obvious effect on GPX4 expression in MCF-7, MDA-MB-453 and MCF-7PR cells^[1].
SB-T-101141 (0.17-16 μM, 3-48 h) induces the total ROS (neutralized by DFOM and NAC), lipid ROS, membrane permeability the impaired cell viability and cell death, not be attenuated by DFOM, Fer-1, or Lip-1, in MCF-7, MDA-MB-453, MCF-7PR and MDA-MB-453PR cells^[1].
SB-T-101141 (3-5 nM, 14 days) significantly inhibits Paclitaxel-resistant MCF-7PR and MDA-MB-231PR cells proliferation^[1].
SB-T-101141 (0.25-1.5 μM, 24 h) induces Paclitaxel-resistant cell death and this effect is only only efficiently inhibited by iron chelators DFOM and CPX in MCF-7PR and MDA-MB-453PR cells^[1].
SB-T-101141(0.001-3 μM, 1-14 days) is more sensitive to MCF-7 cellular with knocking down KHSRP than knocking down HDGF and CYP2S1^[1].
SB-T-101141 (0.01-100 μM, 2-24 h) enhances the thermal stability of KHSRP protein without influence on KHSRP expression in MCF-7 cells^[1].
SB-T-101141 (1.5-3 μM, 0-24 h) promotes lipid peroxidation and effectively reduced the mRNA and protein level of CISD1while increase of 4-HNE level via KHSRP in MCF-7 and MCF-7PR cells^[1].
SB-T-101141 (10 μM, 4 h) prominently exertes ER stress-related G3BP1 granule aggregation, without affecting G3BP1 expression^[1].
SB-T-101141 (0.17-16 μM, 24-48 h) increases protein level of eIF2α and induces cell death via the iron-dependent JNK and PERK signaling with in MCF-7, MDA-MB-453, MCF-7PR and MDA-MB-231PR cells^[1].
In Vivo:SB-T-101141 (5  mg/kg, i.p., once every three days) strongly represses tumor growth in MCF-7(PR)/ MDA-MB-453(PR) xenografted tumor mice mode, without side effects on body weight.^[1].
SB-T-101141 (5  mg/kg, i.p., once every three days) induces no inhibitory activity in tumor growth without increase of aldehyde 4-HNE level in KHSRP knock-down MCF-7 xenografted mice model^[1].