Table 4.

RAF inhibitors

Compound (Pharmaceutical Company)	Tumors	Primary Target(s)	Potential side effects
Bay 43-9006* Sorafenib (Bayer)	Squamous cell carcinoma, Non small cell lung, Leukemia, Hepatocellular carcinoma, Kidney cancer, Pancreatic cancer, Bladder cancer, Lung cancer, Urothelial cancer, Neuroendocrine tumors, Thyroid cancer, Renal cell carcinoma	C-Raf B-Raf B-Raf V600E	Fatigue, Anorexia, Diarrhoea, Nausea, Skin reaction, Alopecia, Rash, Stomatitis, Elevated bilirubin, Pancreatitis
LErafAON (NeoPharm, Inc)	Different advanced malignancies	C-Raf	Back Pain, Chills Fatigue, Hypertension, Fever, Flushing, Dyspnea
ISIS 5132 (Isis Pharmaceuticals)	Ovarian cancer, Breast cancer	C-Raf	Minimal side effects
PLX4720 (Plexxikon/Roche)	Melanoma	B-Raf V600E	Minimal side effects, further studies are needed
PLX4032 (Plexxikon/Roche)	Malignant melanoma, Colorectal carcinoma	B-Raf B-Raf V600E	Cutaneous side effects, Arthralgia, Fatigue
Raf-265 (Novartis Oncology)	Metastatic Melanoma	Raf	Recruiting phase
XL281 (Exelixis)	Non small cell lung cancer, Colorectal cancer, Melanoma, Papillary thyroid cancer	Raf	Recruiting phase
GDC-0879 (Genentech)	Melanoma	Raf	Preclinical Phase Studies
GSK2118436 (GlaxoSmithKline)	Melanoma	B-Raf V600E	Nausea, Fatigue, Fever, Rash, SCC, Headache

WT, wild type,

^*sorafenib is a multityrosine kinase inhibitors, which inhibits additional targets such as, VEGFR2, drugs target additional markers. SCC, squamous cell carcinoma. Another novel multikinase inhibitor is BAY 73-4506 (Regorafenib), which potently inhibits endothelial cell kinases in biochemical and cellular kinase phosphorylation assays. Furthermore, regorafenib inhibits additional angiogenic kinases such as VEGFR1/3, platelet-derived growth factor receptor-β and FGFR 1 and the mutant oncogenic kinases KIT, RET and BRAF. This compound exhibited potent dose-dependent tumor growth inhibition in various preclinical human xenograft models in mice, with tumor shrinkages observed in breast MDA-MB-231 and renal carcinoma models.