NCT-503

**NCT-503** is a chemically synthesized, selective small-molecule inhibitor of **phosphoglycerate dehydrogenase (PHGDH)**, an enzyme that catalyzes the first, rate-limiting step in the de novo serine biosynthesis pathway from glucose-derived 3-phosphoglycerate. It functions by binding to PHGDH and blocking its activity, thereby reducing serine synthesis[1][5]. Preclinical studies reveal that NCT-503 is selective for PHGDH with minimal cross-reactivity for other dehydrogenases and G-protein-coupled receptors[1]. NCT-503 demonstrates anticancer efficacy in PHGDH-dependent cancer cell lines and xenograft mouse models, attenuating tumor growth without significant toxicity or weight loss in treated mice[1][5]. It has also shown synergistic effects in combination with other metabolic inhibitors (e.g., PKM2-IN-1)[2]. Notably, NCT-503 displays some off-target metabolic effects on TCA (tricarboxylic acid) cycle intermediates independent of PHGDH expression, suggesting additional mechanisms beyond PHGDH inhibition[3]. NCT-503 is considered a research probe and has not advanced to clinical trials[1].