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SHIN1 is an inhibitor of serine hydroxymethyltransferase 1 (SHMT1) and SHMT2 (IC50s = 5 and 13 nM, respectively).1 It inhibits proliferation of H1299 non-small cell lung cancer (NSCLC) cells overexpressing the proto-oncogene FRAT1 (IC50 = 0.6 µM). SHIN1 decreases tumor volume in an NSCLC mouse xenograft model using FRAT1-overexpressing H1299 cells when administered at a dose of 100 mg/kg three times a week.
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1. Suppression of nuclear GSK3 signaling promotes serine/one-