SHIN1

SHIN1 is a potent, cell-permeable small molecule inhibitor that targets both human serine hydroxymethyltransferase 1 and 2 (SHMT1/2), key enzymes in one-carbon (1C) metabolism. SHIN1 acts as a folate-competitive antagonist at the SHMT1/2 enzymes, disrupting serine-to-glycine conversion and 1C unit generation, and exhibiting nanomolar inhibitory activity[1][4][8]. Developed from a pyrazolopyran scaffold originally used for plant SHMT inhibition, SHIN1 is specific for human SHMT1/2 and has shown pronounced activity in cancer cell lines—where it induces nucleotide depletion, impairs cell proliferation, and reveals synthetic lethal vulnerabilities in cells reliant on 1C metabolism. SHIN1's metabolic selectivity makes it effective against some tumors and has also demonstrated synergistic effects with DNA and RNA synthesis inhibitors as well as agents like methotrexate or 5-fluorouracil in preclinical studies[5][7]. Due to rapid clearance, SHIN1 is currently unsuitable for in vivo therapeutic use, but serves as a research tool for studying folate and glycine metabolism in vitro[3][4]. Its chemical name is 6-Amino-1,4-dihydro-4-[5-(hydroxymethyl)[1,1'-biphenyl]-3-yl]-3-methyl-4-(1-methylethyl)pyrano[2,3-c]pyrazole-5-carbonitrile[6].

Brand names

SHIN1SHIN-1SHIN 1

Other names

SHIN1SHIN-1SHIN 1RZ-2994RZ2994RZ 2994