Recent advances of RAF (rapidly accelerated fibrosarcoma) inhibitors as anti-cancer agents

• Published in: European journal of medicinal chemistry Vol. 158; pp. 144 - 166
• Main Authors: Ammar, Usama M., Abdel-Maksoud, Mohammed S., Oh, Chang-Hyun
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 05.10.2018
• Subjects: Animals; Anti-cancer agents; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Drug Discovery; Humans; MAP Kinase Signaling System - drug effects; MAPK; Models, Molecular; Neoplasms - drug therapy; Neoplasms - metabolism; Neoplasms - pathology; Protein Kinase Inhibitors - chemistry; Protein Kinase Inhibitors - pharmacology; Protein Kinase Inhibitors - therapeutic use; RAF inhibitors; raf Kinases - antagonists & inhibitors; raf Kinases - chemistry; raf Kinases - metabolism; Bcl-2; FDA; Scr; COX-2; DFG; RAS; SAR; PKC-α; CNS; Abl; INF-β; STKs; RAF inhibitors; Anti-cancer agents; PDGFR; VEGFR; FBDD; UV; EGF; PKB; NRTKs; MAPK; RTKs; FGFR; CR; MEK; RCC; CRD; JAK; RAF; ATP; ERK
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2018.09.005

Frequent oncogenic mutations have been identified in MAPK (mitogen-activated protein kinase) signaling pathway components. As a result, MAPK pathway is associated with human cancer initiation, in particular RAF (rapidly accelerated fibrosarcoma) component. The mutation in RAF component leads to auto-activation of MAPK signaling pathway, stimulating the uncontrolled cell growth and proliferation. In last few years, diverse chemical scaffolds have been identified as RAF inhibitors. Most of these scaffolds show potent anti-cancer activity. The present review highlights the recent investigations of RAF inhibitors during the last five years. [Display omitted] •MAPK signaling pathway activation contributes to stimulation of cell proliferation.•RAF kinases are considered as key components in MAPK signaling pathway.•RAF protein kinase mutation triggers the auto-activation of MAPK signaling pathway.•RAF inhibitors exhibit potent anti-cancer activity.•The present review provides the recent progress in RAF inhibitors identification.