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Fatty acid synthase (FASN) inhibitors block the enzyme that assembles palmitate from acetyl and malonyl units. FASN is a large homodimeric protein that carries all catalytic steps of fatty acid synthesis on one polypeptide chain. Many tumor cells express high FASN levels and rely on de novo lipogenesis, so the enzyme is studied in cancer metabolism. C75, a synthetic α-methylene-γ-butyrolactone, was described in 2000 as a FASN inhibitor tested in xenografts. Orlistat, known as a pancreatic lipase inhibitor, was shown in 2004 to inhibit the thioesterase domain of FASN. Denifanstat, TVB-3166 and TVB-3664 are later reversible FASN inhibitors from a related chemical series. The list also includes natural products reported to inhibit FASN, such as dihydrocurcumin and praeruptorin B.
Leelamine hydrochloride is a tricyclic diterpene molecule that is extracted from the bark of pine trees. Leelamine hydrochloride is a cannabinoid receptor type 1 (CB1) agonist and a inhibitor of SREBP1-regulated fatty acid/lipid synthesis in prostate cancer cells that is not affected by androgen receptor status.
