Princeton University

Gregory S Ducker

Joshua D Rabinowitz

Hahn Kim

Jonathan M Ghergurovich

Jing Fan

The disclosure provides compounds. In certain embodiments, compounds of the disclosure are capable of inhibiting a mammalian SHMT, such as human SMHT1 and/or SHMT2. Compounds of the disclosure have numerous uses.

SHMT inhibitors

A 10-formyl-THF pathway for producing NADPH is useful in the diagnosis and treatment of cancer and metabolic disease, in the development of new antineoplastic agents and/or regimens, in the development of new methods for measuring metabolic pathway activity, and in the development of new therapeutics for treating metabolic disease.

NADPH production by the 10-formyl-THF pathway, and its use in the diagnosis and treatment of disease

The disclosure provides compounds of Formulae (I)-(IX). The disclosed compounds are capable of inhibiting a mammalian SHMT. Compounds of the disclosure have numerous uses, such as for treatment of cancer or autoimmune disorders.

The present invention relates to a method for the treatment of cancer or an autoimmune disorder, comprising the administration of a serine hydroxymethyltransferase (SHMT) inhibitor, and in particular the administration of pyrazolopyran compounds of Formula (VI) as presently described, wherein the compounds are capable of inhibiting a mammalian SHMT, such as human SHMT1 and/or SHMT2. The treatment method further comprises the optional administration of an additional agent as a rescue therapy to reduce toxicity, wherein said agent may be chosen from formate, a formate salt, folinic acid, formate ester, or leucovorin.

The disclosure provides compounds of Formulae (I)-(IX). The disclosed compounds are capable of inhibiting a mammalian SHMT. Compounds of the disclosure have numerous uses, such as for treatment of cancer or autoimmue disorders.

Growing community of inventors

Rocky Hill, NJ, United States of America

Gregory S Ducker