TVB-3166

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[1].

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

IC50: 42 nM (FASN) and 81 nM (cellular palmitate synthesis)[1]

TVB-3166 (0.001-10 μM; 24 hours) causes cell death in CALU-6 non-small-cell lung tumor cells with a cellular IC50 value of 0.10 μM[1]. TVB-3166 (0.02 or 0.20 μM; 7 days) inhibits palmitate synthesis and tumor cell viability in a dose-dependent manner[1]. TVB-3166 (0.2 μM; 48 hours) inhibits β-catenin pathway signal transduction and transcriptional activity[1]. Cell Proliferation Assay[1] Cell Line: CALU-6 tumor cells Concentration: 0.001, 0.01, 0.1, 1, 10 μM Incubation Time: 24 hours Result: Caused cell death in CALU-6 non-small-cell lung tumor cells with a cellular IC50 value of 0.10 μM. Cell Viability Assay[1] Cell Line: 90 different tumor cell lines (such as CALU-6 NSCLC cell line, NCI-H1975 NSCLC cell line) Concentration: 0.02 or 0.20 μM Incubation Time: 7 days Result: Dose-dependent induction of cell death was observed in all tumor cell lines. Western Blot Analysis[1] Cell Line: COLO-205 and A549 cells Concentration: 0.2 μM Incubation Time: 48 hours Result: Inhibited β-catenin pathway signal transduction and transcriptional activity.

TVB-3166 (Oral gavage; 30-100 mg/kg/day) inhibits xenograft tumor growth[1]. TVB-3166 (Oral gavage; 30-100 mg/kg/day) has the concentration is approximately 3-fold higher in plasma than tumor. The 100 and 30 mg/kg groups had plasma and tumor concentrations of 7 and 2.9 μM, respectively[1]. Animal Model: Female BALB-c-nude mice[1] Dosage: 30, 60, or 100 mg/kg Administration: Oral gavage; once daily Result: Inhibited xenograft tumor growth. Animal Model: Female BALB-c-nude mice[1] Dosage: 30, 60, or 100 mg/kg (Pharmacokinetic Study) Administration: Oral gavage; once daily Result: The concentration was approximately 3-fold higher in plasma than tumor. The 100 and 30 mg/kg groups had plasma and tumor concentrations of 7 and 2.9 μM, respectively.

[1]. Ventura R, et al. Inhibition of de novo Palmitate Synthesis by Fatty Acid Synthase Induces Apoptosis in Tumor Cells by Remodeling Cell Membranes, Inhibiting Signaling Pathways, and Reprogramming Gene Expression. EBioMedicine. 2015 Jul 2;2(8):808-24.