CBR-5884 (681159-27-3) is a potent and selective inhibitor of 3-phosphoglycerate dehydrogenase (PHGDH), IC50=33 μM1. The action of PHGDH is the first committed step of serine biosynthesis2 and certain cancer cells overexpress PHGDH3. CBR-5884 inhibits serine biosynthesis in cells with no effect on two other dehydrogenases, lactate dehydrogenase and MDH1 and without general cytotoxic effects up to 40 μM. CBR-5884 is selectively toxic to tumor cells with high serine synthesis activity. A novel tool for selective inhibition of serine biosynthesis in cells which also provides further proof that PHGDH is a viable target for the development of novel anticancer agents1.
1) Mullarky et al. (2016), Identification of a small molecule inhibitor of 3-phosphoglycerate dehydrogenase to target serine biosynthesis in cancers; Proc. Natl. Acad. Sci. USA, 113 1778
2) Snelll et al. (1986), The duality of pathways for serine biosynthesis is a fallacy; Trends Biochem. Sci., 11(6) 241
3) DeNicola et al. (2015), NFR2 regulates serine biosynthesis in non-small cell lung cancer; Nat. Genet., 47 1475