BAY 43-9006: preclinical data.
The drug design and discovery efforts described in the previous section led to the development of a novel, small molecule Raf-1 kinase inhibitor, BAY 43-9006, which belongs to a class that can be broadly described as bis-aryl ureas (Figure 1). BAY 43-9006 was identified during a large medicinal chemistry optimization program, and this compound was selected for further pharmacological characterization based on its potent inhibition of Raf-1 (IC(50) 12 nM) and its favorable kinase selectivity profile. In vitro and in vivo experiments were designed to demonstrate effective blockade of the Raf/MEK/ERK signaling pathway in tumor cells and for anti tumor efficacy in human xenograft models.
D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D001557:Benzenesulfonates / Q000493:pharmacokinetics / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D018450:Disease Progression; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D010766:Phosphorylation / Q000187:drug effects; D019908:Proto-Oncogene Proteins c-raf / Q000037:antagonists & inhibitors / Q000502:physiology; D011725:Pyridines / Q000493:pharmacokinetics / Q000494:pharmacology*; D000077157:Sorafenib
D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D011725:Pyridines; D009536:Niacinamide; D000077157:Sorafenib; D019908:Proto-Oncogene Proteins c-raf