molecules of the month

compound 19

oral DHODH inhibitor

tumor growth inhibition in xenograft models

from virtual screening and SBDD

J. Med. Chem.

Janssen, Spring House, PA

compound 19 chemical structure oral DHODH inhibitor - Janssen, Spring House, PA
5 mins read

Context. “Compound 19” (Janssen) is an oral dihydroorotate dehydrogenase (DHODH) inhibitor being developed for acute myelogenous leukemia (AML). DHODH is a ubiquitously expressed, essential enzyme in the de novo pyrimidine biosynthesis pathway. Despite its ubiquitous expression and lack of known mutations or overexpression in cancer, DHODH has been explored as a potential target, primarily because malignant cells seem to be more reliant on de novo pyrimidine biosynthesis. Although DHODH inhibitors have been explored is solid tumors, their use in liquid tumors, such as AML, is much more promising.  Fewer than 30% of patients survive for more than 5 years with AML. One hallmark of AML is cell differentiation arrest, and treatment of AML patients with acute promyelocytic leukemia (APL) with…

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