Spliceostatin A

Spliceostatin A, the FR901464 (HY-16212) methylated derivative, is a potent anti-tumor agent. Spliceostatin A inhibits splicing and promotes pre-mRNA accumulation by binding SF3B1. SF3B1 is a subcomplex of U2 small nuclear ribonucleoprotein in the spliceosome. Spliceostatin A induces Apoptosis in chronic lymphocytic leukemia (CLL) cells[1][2][3].

Research Areas >> Cancer

Signaling Pathways >> Others >> Others

IC50: 5.5 nM (wild-type SF3B1), 4.9 nM (SF3B1mutatant)[1]

Spliceostatin A (2.5-20 nM; 0-24 h) 以剂量和时间依赖的方式诱导 CLL 细胞出现 Caspase 依赖性凋亡[1]。 Spliceostatin A (10 nM, 20 nM; 24 h) 与 ABT-199 或 ABT-263 有协同作用，增加 IL4/CD40L (10 ng/mL, 300 ng/mL;6 h) 处理后 CLL 细胞的凋亡，并降低相关蛋白磷酸化水平[1]。 Spliceostatin A 抑制正常 B (CD19+) 和 T (CD3+) 淋巴细胞的活力，IC50 分别为 12.1 nM 和 61.7 nM[1]。 Apoptosis Analysis[1] Cell Line: CLL cells Concentration: 0, 2.5 nM, 5 nM, 10 nM, and 20 nM Incubation Time: 0, 6 h, 12 h, and 24 h Result: Increased cell apoptosis. Western Blot Analysis[1] Cell Line: CLL cells Concentration: 10 nM, and 20 nM Incubation Time: 24 h; treated after 10 ng/mL IL4 and/or 300 ng/mL CD40L for 6 h Result: Decreased the level of PARP, phosphorylated STAT6 (pSTAT6), phosphorylated IκBα (pIκBα), Mcl-1L, Bcl-xL , Bcl-2 and Hsc70.

[1]. Larrayoz M, et al. The SF3B1 inhibitor spliceostatin A (SSA) elicits apoptosis in chronic lymphocytic leukaemia cells through downregulation of Mcl-1. Leukemia. 2016 Feb;30(2):351-60.  

[2]. Kaida D, et al. Spliceostatin A targets SF3b and inhibits both splicing and nuclear retention of pre-mRNA. Nat Chem Biol. 2007 Sep;3(9):576-83.  

[3]. Roybal GA, et al. Spliceostatin A inhibits spliceosome assembly subsequent to prespliceosome formation. Nucleic Acids Res. 2010 Oct;38(19):6664-72.