Princeton University

Glaxosmithkline LLC

Jonathan M Ghergurovich

Joshua D Rabinowitz

Nicholas D Adams

Cynthia A Parrish

Kenneth Wiggall

Hahn Kim

Christopher Joseph Aquino

Gregory S Ducker

Alexander Joseph Reif

Amita M Chaudhari

Terence John Kiesow

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

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.

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Philadelphia, PA, United States of America

Jonathan M Ghergurovich