Drug intelligence / Profile preview

spliceostatin A

Development stage
Preclinical
Lead developer
Astellas Pharma
Modality
Small Molecules
Administration
Intravenous
01

Overview

Spliceostatin A (SSA) is a potent small molecule spliceosome inhibitor and a methylated derivative of the natural product FR901464, which was originally isolated from *Pseudomonas* sp. No. 2663. SSA exerts its biological activity by binding to the SF3b complex, a critical component of the U2 small nuclear ribonucleoprotein (snRNP), specifically targeting the SF3B1 subunit. This interaction interferes with the recognition of the pre-mRNA branch point sequence, leading to widespread inhibition of splicing and the accumulation of unspliced pre-mRNAs. In preclinical research, SSA has demonstrated significant anti-tumor activity, inducing cell cycle arrest in the G1 and G2/M phases and promoting apoptosis in various cancer cell lines, including acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). Due to its high potency and specific mechanism, SSA is widely utilized as a chemical probe to investigate the role of the spliceosome in gene expression and disease pathology.

02

Targets

SF3B1 (Splicing factor 3B subunit 1)

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