Uses
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].
Biochem/physiol Actions
TVB-3166 is a cell-permeable pyrrazole derivative that inhibits cellular palmitate synthesis (IC50 <100 nM) by fatty acid synthase (FASN) keto-reductase activity in a potent and reversible manner (IC50 = 42 nM), effectively inhibiting palmitate-dependent survival of various cancer cells in cultures and xenografted tumor growth in mice vivo (60-100 mg/kg/d p.o.), while exhibiting little or no anti-proliferation activity toward non-palmitate-dependent growth of cancer and non-cancer cultures. FASN inhibition by TVB-3166 treatment is also effective against the replications respiratory viruses both in cultures (Effc. conc. 200 nM against RSV and PIV3 in A549, HEp2, and HeLa cultures) and in mice (50 mg/kg/12 h, p.o.; RSV) in vivo without significant adverse effects to the host cells or mice.
in vivo
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.
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| 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. |
References
[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. DOI:
10.1016/j.ebiom.2015.06.020
