NXT629

NXT629 is a potent, selective, and competitive PPAR-α antagonist, with an IC₅₀ of 77 nM for human PPARα, shows high selectivity over other nuclear hormone receptor, such as PPARδ, PPARγ, ERβ, GR and TRβ, IC₅₀s are 6.0, 15, 15.2, 32.5 and >100 μM, respectively^[1]. NXT629 has potent anti-tumor activity and inhibits experimental metastasis of cancer cell in animal models^[2]. In Vitro: NXT629 (Compound 33) is a potent, selective PPAR-α antagonist, with an IC₅₀ of 77 nM for human PPARα, shows high selectivity over other nuclear hormone receptor, such as PPARδ, PPARγ, Erβ, GR and TRβ, IC₅₀s are 6.0, 15, 15.2, 32.5 and >100 μM, respectively^[1]. NXT629 also competitively inhibits mousse PPARα, PPARβ/δ and PPARγ, with IC₅₀s of 2.3, 35.1, 6.9 μM, resepctively^[2]. In Vivo: NXT629 (Compound 33; 30 mg/kg, i.p.) exhibits good pharmacokinetics in mouse, and significantly decreases Fgf21 (Fibroblast growth factor 21), a PPARα target gene in fasted mice^[1].
NXT629 has poor oral bioavailability in mice and rats. NXT629 (30 mg/kg, i.p., daily for 6 weeks) delays growth of subcutaneous SKOV-3 tumors in nude mice, inhibits growth of subcutaneous B16F10 tumors in C57Bl/6 mice. NXT629 (30 mg/kg, i.p.) is weakly anti-angiogenic against FGF-induced angiogenesis. NXT629 (3, 30 mg/kg, i.p.) inhibits experimental metastasis of B16F10 melanoma cells to the mouse lung^[2].