GW 6471

GW 6471 is a potent dual PARα/γ antagonist with anti-proliferative activity in vivo and in vitro. The IC₅₀ values of GW 6471 binding affinity to PPARα and PPARγ are 95.3 ± 42.0 nM and 39.4 ± 18.2 nM, respectively^[1]. GW 6471 can be used in cancer research^[1-3].

GW 6471 inhibits the growth (0.5 μM to 8 μM), migration and invasion (0.5 μM to 10 μM) of human mesothelioma cells and, at higher concentrations, reduces the viability of human mesothelioma cell line VGE62 and murine mesothelioma cell lines AB1 and AE17^[1]. GW 6471 reduces HNPGL cell viability and growth by inducing cell cycle arrest and caspase-dependent apoptosis with IC₅₀ values of 10 μM and 16 μM in PTJ64i and PTJ86i cells, respectively. The effect of GW 6471 on HNPGL cells is associated with inhibition of the PI3K/GSK3β/β-catenin signaling pathway^[2].

GW 6471 (20 mg/kg) inhibited tumor growth in Caki-1 cell xenograft mouse models and the expression of c-Myc in mouse tumor tissues. No toxicity was observed at a dose of 20 mg/kg, and renal and liver functions were not adversely affected^[3]. Medial prefrontal cortex injection of GW6471 (10 μg) in rats delayed the onset of the early second phase of formalin-induced nociceptive behavior^[4].

References:
[1] Morales M L O, Rinaldi C A, de Jong E, et al. PPARα and PPARγ activation is associated with pleural mesothelioma invasion but therapeutic inhibition is ineffective[J]. Iscience, 2022, 25(1).
[2] Florio R, De Lellis L, di Giacomo V, et al. Effects of PPARα inhibition in head and neck paraganglioma cells[J]. PLoS One, 2017, 12(6): e0178995.
[3] Abu Aboud O, Donohoe D, Bultman S, Fitch M, Riiff T, Hellerstein M, Weiss RH. PPARα inhibition modulates multiple reprogrammed metabolic pathways in kidney cancer and attenuates tumor growth. Am J Physiol Cell Physiol. 2015 Jun 1;308(11):C890-8.
[4] Okine B N, Rea K, Olango W M, et al. A role for PPAR α in the medial prefrontal cortex in formalin‐evoked nociceptive responding in rats[J]. British journal of pharmacology, 2014, 171(6): 1462-1471.