indisulam

Indisulam is a small molecule sulfonamide derivative developed as an antitumor agent. It acts primarily as a molecular glue that induces the proteasomal degradation of the mRNA splicing factor RBM39 (also known as CAPERα) by recruiting it to the DCAF15-containing cullin-RING E3 ubiquitin ligase complex, leading to aberrant pre-mRNA splicing and cell cycle arrest in cancer cells[3][4][6][10]. Indisulam has demonstrated anticancer activity in vitro and in animal models, particularly against hematological malignancies such as acute myeloid leukemia (AML), high-risk myelodysplastic syndrome (MDS), and T-cell acute lymphoblastic leukemia (ALL)[5][6][7]. Its mechanism also involves upregulation of p53 and p21, G1-S cell cycle arrest, apoptosis induction, and inhibition of carbonic anhydrase XII[3][4]. Developed by Eisai, indisulam has been evaluated in multiple phase 1/2 clinical trials for relapsed/refractory AML/MDS and solid tumors but is not currently approved for any indication[2][7].

Other names

indisulam