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]. IC50 & Target:IC50: 42 nM (FASN) and 81 nM (cellular palmitate synthesis)^[1] In Vitro: ISX-9 promotes neurogenesis in vivo, enhancing the proliferation and differentiation of hippocampal subgranular zone (SGZ) neuroblasts, and the dendritic arborization of adult-generated dentate gyrus neurons. At 2.5-20 μM, ISX-9 has been shown to dose-dependently trigger neurogenesis and block gliogenesis in adult rat hippocampal stem cells through a calcium-activated signaling pathway dependent on myocyte-enhancer factor 2-dependent gene expression^[1].
Molecular exploration of ISX-9-induced regulation of neurogenesis (via FACS and microarray of SGZ stem and progenitor cells) suggested the involvement of the myocyte-enhancer family of proteins (Mef2)^[1]. 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].