Cevoglitazar is a dual agonist for the peroxisome proliferator-activated receptor (PPAR)-alpha and -gamma subtypes. Cevoglitazar was as effective as pioglitazone at improving glucose tolerance, normalizes intramyocellular lipids and reduces body weight gain and adiposity, independent of food intake. Metabolic profiling showed that in the muscle cevoglitazar improves the lipid profile via both PPARα‐ and PPARγ‐mediated mechanisms. Cevoglitazar only induced small changes to the lipid composition of visceral fat. In subcutaneous fat, however, cevoglitazar induced changes similar to those observed with fenofibrate suggesting export of fatty acids from this depot.

CHIR-265 (RAF265) is a potent selective orally active small molecule Raf-kinase inhibitor with anti‐angiogenic activity through inhibition of vascular endothelial growth factor type 2 (VEGFR‐2) in preclinical models. CHIR-265 effectively block phosphorylation of Raf's downstream substrates MEK and ERK in cells and also kill melanoma and colorectal cancer cell lines harboring B-Raf mutations independent of PTEN mutation status. Raf kinase inhibition by CHIR-265 in mutant B-Raf melanoma cell lines causes cell cycle arrest and induces apoptosis, mimicking the effect of Raf RNAi in these cells. CHIR-265 also potently inhibits the phosphorylation of VEGFR2 and proliferation of VEGF-stimulated hMVEC.