Inhibition of proline catabolism for the treatment of cancer and other therapeutic applications
AssigneeBuck Institute for Research on Aging
InventorsGary K. Scott, Christopher C. Benz
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Abstract
In various embodiments a cancer treatment method is provided based on inhibition of proline catabolism. When combined with p53 restoration therapy and/or inhibition of glutaminase, the inhibition of proline catabolism results in a “synthetic lethal” and synergistic anticancer response. Novel suicide inhibitors that induce the degradation of proline dehydrogenase (PRODH) are also provided. Also provided is a method of assaying PRODH to identify responders/non-responders to inhibition of proline catabolism and/or glutaminase.
Claims19
An analog of N-propargylglycine (PPG) that is capable of occupying the proline binding pocket of proline dehydrogenase (PRODH) and forming a covalent bond with PRODH or a flavin adenine dinucleotide (FAD) cofactor of PRODH, wherein the PPG analog comprises a compound with the formula:
- wherein R1 is selected from the group consisting of H, C1-C4 alkyl, halogen, and C1-C4 haloalkyl.
Dependencies are inferred from the claim text.