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].

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].

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].

[1]. Bravo Y, et al. Identification of the first potent, selective and bioavailable PPARα antagonist. Bioorg Med Chem Lett. 2014 May 15;24(10):2267-72. [2]. Stebbins KJ, et al. In vitro and in vivo pharmacology of NXT629, a novel and selective PPARα antagonist. Eur J Pharmacol. 2017 Aug 15;809:130-140.