TVB-3664 is an orally active, selective, reversible, and highly bioavailable fatty acid synthase inhibitor (FASN) with an IC50 for palmitate synthesis of 18 nM in human and 12 nM in mouse.Significantly inhibits microtubule protein palmitoylation and mRNA expression.

FASN:18 nM

METHODS: CaCo2, HT29 and LIM2405 cells were treated with TVB-3664 in cell line-specific medium supplemented with 10% FBS for 7 days without medium change and cell proliferation was assessed by cell counting.
RESULTS TVB-3664 inhibited the proliferation of CaCo2, HT29 and LIM2405 cells. [1]
METHODS: Primary CRC cells from Pt 93 and Pt 130 were treated with 0.2 μM TVB-3664 for 6 days under normal or serum-starved conditions and labeled with CD36-FITC antibody. Perform flow cytometric analysis.
RESULTS Inhibition of FASN activity by TVB-3664 resulted in an increase in membrane-associated CD36 compared to control cells under normal and serum-poor conditions. [2]

METHODS: Animals were treated with 3 mg/kg (Pt 2614 and Pt 2449PT) or 6 mg/kg (Pt 2402 and Pt 2449LM) of TVB-3664 daily by oral gavage.
RESULTS TVB-3664 treatment significantly reduced the tumor volume and tumor weight of Pt 2614, Pt 2449PT and Pt 2402 PDX models, with average tumor weight reductions of 30%, 37.5% and 51.5% respectively. [1]
METHODS: To assess the correlation between activation of major oncogenic pathways and tumor responses in vivo, the levels of pAkt, pAMPK, pErk1/2, and TIP47 in tumor tissues in the G0 PDX model were analyzed.
RESULTS TVB-3664 treatment induced the activation of pAkt and pAMPK, but reduced the level of TIP47 in the Pt 2387 model; analysis of tumor samples of TVB-3664-treated Pt 2377PT and LM models showed that the activation of pErk1/2 and pAMPK, respectively Increase. [1]
METHODS: A trial was conducted using the H2122 mouse xenograft model, in which we dosed mice with 5 mg/kg TVB-3664 and 10 mg/kg MRTX849 for approximately 3 weeks.
RESULTS The weight of the mice remained stable throughout. The combined treatment was significantly better than the single drug group and could prevent tumor growth. [2]