NCT-503是phosphoglycerate dehydrogenase (PHGDH)抑制剂，IC50为2.5 μM。NCT-503对其他脱氢酶基本没有活性，对所检测的168种GPCRs没有或仅具有微弱的交叉反应性。 Information NCT-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. Targets PHGDH (Cell-free) 2.5 μM In vitro NCT-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 vivo NCT-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.