CBR-5884 is a potent and selective inhibitor of 3-phosphoglycerate dehydrogenase (PHGDH), IC50=33 μM. The action of PHGDH is the first committed step of serine biosynthesis?and certain cancer cells overexpress PHGDH. 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 agents.?
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