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The patent issued for ACSS2 inhibitors and methods of use thereof by EpiVario Inc. focuses on targeting metabolic vulnerabilities in cancer cells, particularly those expressing ACSS2, to develop new anticancer therapeutics. The invention aims to suppress tumor growth by inhibiting acetyl-CoA synthesis from acetate, which is crucial for cancer cell survival under hypoxic conditions. Additionally, the patent suggests potential applications in treating alcoholism by targeting ACSS2. The research highlights the importance of metabolic enzymes in cancer therapy and offers promising avenues for future treatments. [Extracted from the article]

Inactivating mutations in any of the SDH subunits, or the SDH complex assembly factor (SDHAF2), are associated with susceptibility to develop neuroendocrine neoplasms and gastrointestinal stromal tumors as well as renal cell carcinoma. These SDH gene alterations, lead to the loss of enzyme activity and expression, and observed in several tumors such as renal cell carcinoma, gastrointestinal stromal tumors, colorectal cancer, gastric cancer, and ovarian cancer. In other embodiments, the cancer is familial, sporadic, early cancer, advanced cancer, invasive cancer, metastatic cancer, drug resistant cancer or any combination thereof. [Extracted from the article]

"This invention further provides a method of binding an ACSS2 inhibitor compound to an ACSS2 enzyme, comprising the step of contacting an ACSS2 enzyme with an ACSS2 inhibitor compound represented by the structure of formula I-III(a), and by the structures listed in Table 1, as defined herein below, in an amount effective to bind the ACSS2 inhibitor compound to the ACSS2 enzyme. The nucleocytosolic acetyl-CoA synthetase enzyme, ACSS2, supplies a key source of acetyl-CoA for tumors by capturing acetate as a carbon source. In various embodiments, the tumor growth is suppressed due to suppression of lipid (e.g., fatty acid) synthesis and/or histones synthesis induced by ACSS2 mediated acetate metabolism to acetyl-CoA. [Extracted from the article]