PF-06840003

Description: PF-06840003 (also known as EOS200271) is a highly potent and selective, orally bioavailable IDO-1 inhibitor with IC50 of 0.15 uM. It is a tryptophan analog, noncompetitive, and non-heme-binding IDO1 inhibitor licensed by iTeos SA to Pfizer for clinical development. Tumors use tryptophan-catabolizing enzymes such as indoleamine 2, 3-dioxygenase (IDO-1) to induce an immunosuppressive environment. IDO-1 is induced in response to inflammatory stimuli and promotes immune tolerance through effector T-cell anergy and enhanced Treg function. As such, IDO-1 is a nexus for the induction of a key immunosuppressive mechanism and represents an important immunotherapeutic target in oncology. PF-06840003 has favorable human pharmacokinetic characteristics, a prolonged human half-life that may allow single-dose daily administration, and CNS penetration. PF-0684000 has moderate hIDO1 enzyme inhibition with IC50 0.41 uM. It is a highly efficient compound which is driven by its tight packing within the enzyme, as well as the high density of hydrogen bonds it forms with hIDO-1 despite its small size.

References: AACR; Cancer Res 2016; 76(14 Suppl):Abstract nr4863.