SHIN2

SHIN2 is a novel, potent small-molecule inhibitor that targets both the cytosolic (SHMT1) and mitochondrial (SHMT2) isoforms of serine hydroxymethyltransferase, key enzymes involved in folate-mediated one-carbon (1C) metabolism and nucleotide biosynthesis. It was developed as an improved analog of SHIN1, optimized for pharmacokinetics suitable for in vivo studies. SHIN2 demonstrates strong antiproliferative activity against T-cell acute lymphoblastic leukemia (T-ALL) cell lines and increases survival in mouse models of NOTCH1-driven T-ALL. It shows synergistic antileukemic effects when combined with methotrexate and may be effective in methotrexate-resistant disease. Mechanistically, SHIN2 blocks proliferation by depleting 1C units and intracellular glycine, resulting in S-phase cell cycle arrest with little cytotoxicity.

Other names

AOB11286AOB-11286AOB 11286