Fatty Acid Synthase (FASN) Inhibitor

Fatostatin (125B11), a specific inhibitor of SREBP activation, impairs the activation of SREBP-1 and SREBP-2. Fatostatin binds to SCAP (SREBP cleavage-activating protein), and inhibits the ER-Golgi translocation of SREBPs. Fatostatin decreases the transcription of lipogenic genes in cells. Fatostatin possesses antitumor properties, and lowers hyperglycemia in ob/ob mice.

C75 is a synthetic fatty-acid synthase (FASN) inhibitor; inhibits prostate cancer cells PC3 with an IC₅₀ of 35 μM. C75 is a potent CPT1A activator.

Denifanstat (TVB-2640) is an orally active and potent Fatty Acid Synthase (FASN) inhibitor with an IC₅₀ of 0.052 μM and an EC₅₀ of 0.072 μM. Denifanstat has the potential for fatty liver disease and cancer research.

Orlistat (Tetrahydrolipstatin) is a well-known irreversible inhibitor of pancreatic and gastric lipases. Orlistat is also an inhibitor of fatty acid synthase (FASN), is used orally for long-term research of obesity. Anti-atherosclerotic effect.

Esculeogenin A is the sapogenol of tomato saponin Esculeoside A (HY-N18067). Esculeogenin A is an orally active hepatoprotective, hypolipidemic, and antioxidant agent. Esculeogenin A regulates molecular targets like PPARα, SREBP1, Nrf2, NF-κB, ACAT1/ACAT2 to promote hepatic fatty acid oxidation, suppress de novo lipogenesis, enhance antioxidant defense, and inhibit inflammation. Esculeogenin A improves liver function, alleviates hyperlipidemia, and inhibits hepatic steatosis and foam cell formation, preventing nonalcoholic fatty liver disease in high-fat-diet-fed rats and reducing atherosclerotic lesions in apoE-deficient mice. Esculeogenin A can be used for the research of nonalcoholic fatty liver disease, atherosclerosis, and hyperlipidemia.

Canola oil is an orally effective adipogenesis inhibitor and gut microbiota modulator. Canola oil inhibits the expression of PPARγ, SREBP1, SREBP2, Insig1 and Insig2, and increases the phosphorylation level of the AMPK pathway. Canola oil inhibits adipogenesis and reshapes gut microbiota in mice to ameliorate obesity. Canola oil can be used in obesity-related research.

Cerulenin, a potent, natural inhibitor of fatty acid synthase (FASN), is an epoxide produced by the fungus Cephalosporium caeruleus. Cerulenin inhibits topoisomerase I catalytic activity and augments SN-38-induced apoptosis. Cerulenin has antifungal and antitumor activies.

Lycorine is a natural alkaloid extracted from the Amaryllidaceae plant. Lycorine is a potent and orally active SCAP inhibitor with a K_d value 15.24 nM. Lycorine downregulates the SCAP protein level without changing its transcription. Lycorine is also a melanoma vasculogenic inhibitor. Lycorine can be used for the study of prostate cancer and metabolic diseases.

PF429242 dihydrochloride is a reversible and competitive SREBP site 1 protease (S1P) inhibitor with an IC₅₀ of 175 nM.

Malic enzyme inhibitor ME1 (ME1; compound 1) is a potent inhibitor of Malic enzyme (ME1) with an IC₅₀ of 0.15 μM.

TVB-3166 is an orally-available, reversible, and selective fatty acid synthase (FASN) inhibitor with IC₅₀s of 42 nM and 81 nM for biochemical FASN and cellular palmitate synthesis, respectively. TVB-3166 induces apoptosis, and inhibits in-vivo xenograft tumor growth.

Fatostatin hydrobromide (125B11 hydrobromide), a specific inhibitor of SREBP activation, impairs the activation of SREBP-1 and SREBP-2. Fatostatin hydrobromide binds to SCAP (SREBP cleavage-activating protein), and inhibits the ER-Golgi translocation of SREBPs. Fatostatin hydrobromide decreases the transcription of lipogenic genes in cells. Fatostatin hydrobromide possesses antitumor properties, and lowers hyperglycemia in ob/ob mice.

Ferroheme is the ferrous form of heme in hemoglobin, reversibly binding oxygen as an oxygen carrier. Its free form induces oxidative stress and ferroptosis by releasing iron ions, which catalyze reactive oxygen species generation via Fenton reactions, leading to lipid peroxidation and cell death. This mechanism is critical in pathological contexts like intracerebral hemorrhage and neurodegenerative diseases, making it a target for studying iron-overload disorders and ferroptosis-related pathologies[1][2][3].

Betulin (Trochol), is a sterol regulatory element-binding protein (SREBP) inhibitor with an IC₅₀ of 14.5 μM in K562 cell line.

TVB-3664 is an orally available, reversible, potent, selective and highly bioavailable fatty acid synthase (FASN) inhibitor, with IC₅₀ values of 18 nM and 12 nM for human and mouse cell palmitate synthesis, respectively. TVB-3664 significantly reduces tubulin palmitoylation and mRNA expression.

Desmosterol is a cholesterol-like molecule. In the Bloch pathway of cholesterol biosynthesis, Desmosterol is a direct precursor of cholesterol. As an endogenous metabolite, Desmosterol is used to study cholesterol metabolism . Desmosterol is an LXR activator and SREBP inhibitor, which can suppress macrophage inflammasome activation and prevent vascular inflammation and atherosclerosis. A reduction in Desmosterol promotes the production of mitochondrial reactive oxygen species (ROS) in macrophages and pyrin domain-dependent inflammasome activation of NLRP3. Desmosterol holds potential for research in inflammation, metabolism, and cardiovascular diseases .

GSK2194069 is a potent inhibitor of β-ketoyl reductase (KR) of fatty acid synthase (FASN), with an IC₅₀ value of 7.7 nM. GSK2194069 shows specifically inhibitory effect on FAS expressing cancer cells, by acting potent efficacy on acetoacetyl-CoA, NADPH with IC₅₀ or K_i values of 4.8 nM and 5.6 nM, respectively.

BI 99179, a chemical probe, is a potent and selective type I fatty acid synthase (FAS) inhibitor with an IC₅₀ of 79 nM. BI 99179 is a tool compound suitable for the in vivo validation of FAS as a target for lipid metabolism related diseases. BI 99179 exhibits significant exposure (both peripheral and central) upon oral administration in rats.

Agrimol B, a polyphenol, is an orally active and potent SIRT1 activator. Agrimol B shows anti-adipogenic and anticancer activity. Agrimol B shows antibacterial activity against plant pathogens. Agrimol B dramatically inhibits 3T3-L1 adipocyte differentiation by reducing PPARγ, C/EBPα, FAS, UCP-1, and apoE expression. The action of Agrimol B on the cancer cells is likely derived from its effect on c-MYC, SKP2 and p27.

IPI-9119 is an orally active, selective and irreversible FASN inhibitor with an IC₅₀ of 0.3 nM in vitro biochemical assay. IPI-9119 inhibits tumor growth of castration-resistant prostate cancer (CRPC) xenografts mouse models.