NCT503 是一种磷酸甘油酸脱氢酶 (PHGDH) 抑制剂，其IC50=2.5 μM。

NCT-503 is an inhibitor of 3-phosphoglycerate dehydrogenase (PHGDH), inhibiting serine synthesis from 3-phosphoglycerate in cells.

NCT-503 has reasonable aqueous solubility, and exhibits favorable absorption, distribution, metabolism and excretion (ADME) properties[1]. 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

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

Animal Models: NOD.SCID mice bearing MDA-MB-231 and MDA-MB-468 orthotropic xenograftsFormulation: 5% ethanol, 35% PEG 300, and 60% of an aqueous 30% hydroxypropyl-β-cyclodextrin solutionDosages: 40 mg/kgAdministration: i.p.(Only for Reference)

1916571-90-8

C20H23F3N4S

408.49

NCT 503

H2O:<1 mgml
Ethanol:75 mg/mL (183.6 mM)
DMSO:75 mg/mL (183.6 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years