Discovery and development of sorafenib: a multikinase inhibitor for treating cancer.
Since the molecular revolution of the 1980s, knowledge of the aetiology of cancer has increased considerably, which has led to the discovery and development of targeted therapies tailored to inhibit cancer-specific pathways. The introduction and refinement of rapid, high-throughput screening technologies over the past decade has greatly facilitated this targeted discovery and development process. Here, we describe the discovery and continuing development of sorafenib (previously known as BAY 43-9006), the first oral multikinase inhibitor that targets Raf and affects tumour signalling and the tumour vasculature. The discovery cycle of sorafenib (Nexavar; Bayer Pharmaceuticals) - from initial screening for a lead compound to FDA approval for the treatment of advanced renal cell carcinoma in December 2005 - was completed in just 11 years, with approval being received approximately 5 years after the initiation of the first Phase I trial.
Wilhelm
Scott
S
Department of Cancer Research, Bayer Pharmaceuticals Corp., West Haven, Connecticut 06516, USA. scott.wilhelm.b@bayer.com
Carter
Christopher
C
Lynch
Mark
M
Lowinger
Timothy
T
Dumas
Jacques
J
Smith
Roger A
RA
Schwartz
Brian
B
Simantov
Ronit
R
Kelley
Susan
S
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001557:Benzenesulfonates / Q000494:pharmacology / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy; D002986:Clinical Trials as Topic; D020650:Combinatorial Chemistry Techniques; D015195:Drug Design; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy; D009369:Neoplasms / Q000188:drug therapy*; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011725:Pyridines / Q000494:pharmacology / Q000627:therapeutic use*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors; D000077157:Sorafenib; D048490:raf Kinases / Q000037:antagonists & inhibitors
D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D009536:Niacinamide; D000077157:Sorafenib; D040262:Receptors, Vascular Endothelial Growth Factor; D048490:raf Kinases