Motixafortide(TFA) (C09-0967-746)

InformationMotixafortide (BL-8040, BKT140, TF 14016, 4-fluorobenzoyl, 4F-benzoyl-TN14003, T140) is an antagonist ofCXCR4with IC50 of ～1 nM. BL-8040 induces theapoptosisof AML blasts by down-regulatingERK,BCL-2,MCL-1andcyclin-D1via altered miR-15a/16-1 expression.TargetsERK ; Bcl-2 ; MCL-1 ; cyclin-D1 ; CXCR4 (Cell-free assay) ; 1 nMIn vitroTreatment with BL-8040 induces the robust mobilization of AML blasts from the BM. In addition, AML cells exposed to BL-8040 undergoes differentiation. BL-8040 induces the apoptosis of AML cells in vitro. This apoptosis is mediated by the up-regulation of miR-15a/miR-16-1, resulting in down-regulation of the target genes BCL-2, MCL-1 and cyclin-D1. Overexpression of miR-15a/miR-16-1 directly induces leukemic cell death. BL-8040-induced apoptosis is also mediated by the inhibition of survival signals via the AKT/ERK pathways.In vivoBL-8040 induces the apoptosis of AML cells in vivo. Treatment with a BCL-2 inhibitor induces apoptosis and acts together with BL-8040 to enhance cell death. BL-8040 also synergizes with FLT3 inhibitors to induce AML cell death. Importantly, this combined treatment prolongs the survival of tumor-bearing mice and reduces minimal residual disease in vivo.Cell Research(from reference)Cell lines：The leukemic cell lines (MV4-11, THP-1, U937, HL-60) Concentrations：0.1 μM, 1 μM, 10 μM, 20 μM Incubation Time：24 h, 48 h. Specification: 0.98 Molecular Formula: C97H144FN33O19S2(free base) Molecular Weight: 2159.52(free base) Related Documents: https://ald-pub-files.oss-cn-shanghai.aliyuncs.com/aladdinsci/pdp/sds/1/M414450-SCI_56bf70dc0f3f4f77093a38284e401166.pdf