TS-002455

TS-002455 is a small molecule inhibitor of the terminal uridyltransferases TUT4 (ZCCHC11) and TUT7 (ZCCHC6), which are key regulators of RNA stability and microRNA (miRNA) biogenesis. Developed by 128-7 Therapeutics, TS-002455 is the weakly active enantiomer of the more potent inhibitor TS-002266. In preclinical studies focusing on MLL-rearranged acute myeloid leukemia (AML), inhibition of TUT4/7 has been shown to reduce cell proliferation and sensitize cells to BCL-2 inhibitors like venetoclax. However, TS-002455 itself demonstrated minimal activity in these combination assays, serving primarily as a pharmacological control to validate the stereospecific effects of the active lead compound.