NCT-503 (C007B-392270)

InformationNCT-503 NCT-503 is a phosphoglycerate dehydrogenase (PHGDH) inhibitor with the IC50 value of 2.5 μM. It is inactive against a panel of other dehydrogenases and shows minimal cross-reactivity in a panel of 168 GPCRs.TargetsPHGDH (Cell-free) 2.5 μMIn vitroNCT-503 has reasonable aqueous solubility, and exhibits favorable absorption, distribution, metabolism and excretion (ADME) properties. NCT-503 selectively blocks glucose-derived serine synthesis but at the same time triggers SHMT1-dependent one-carbon unit wasting to synthesize serine from glycine. This futile cycle depletes the cell of nucleotides and leads to cell cycle arrest.In vivoNCT-503 has good exposure (AUClast=14,700 hr*ng/mL), half-life (2.5 hr) and Cmax (~20 µM in plasma) following intraperitoneal administration with significant partitioning into the liver and brain. PHGDH inhibition by NCT-503 selectively increases necrosis in MDA-MB-468 xenografts, but not in MDA-MB-231 xenografts. It also reduces the growth and weight of PHGDH-dependent MDA-MB-468 xenografts but does not affect the growth or weight of PHGDH-independent MDA-MB-231 xenografts. Specification: 0.98 Molecular Formula: C20H23F3N4S Molecular Weight: 408.48 PubChem CID: 118796328 Isomeric SMILES: CC1=CC(=NC(=C1)NC(=S)N2CCN(CC2)CC3=CC=C(C=C3)C(F)(F)F)C Related Documents: https://ald-pub-files.oss-cn-shanghai.aliyuncs.com/aladdinsci/pdp/sds/1/N414084-SCI_225b0487a8e5c228ed5731e6f465a8ff.pdf