Spliceostatin A, the FR901464 metlated 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.
Spliceostatin A (2.5-20 nM; 0-24 h) induces caspase-dependent apoptosis of CLL cells in a dose- and time-dependent manner[1].Spliceostatin A (10 nM, 20 nM; 24 h) in combination with ABT-199 or ABT-263 synergises, augments apoptosis in CLL cells following IL4/CD40L (10 ng/mL, 300 ng/mL; 6 h) treatment, and reduce phosphorylation levels of related proteins[1].Spliceostatin A inhibits the viability of normal B (CD19+) and T (CD3+) lymphocytes with IC50s of 12.1 nM, and 61.7 nM, respectively[1].
References:
[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.