title: PI3K/Akt/mTOR and Ras/Raf/MEK/ERK signaling pathways inhibitors as anticancer agents: Structural and pharmacological perspectives.
abstract: The protein kinases regulate cellular functions such as transcription, translation, proliferation, growth and survival by the process of phosphorylation. Over activation of signaling pathways play a major role in oncogenesis. The PI3K signaling pathway is dysregulated almost in all cancers due to the amplification, genetic mutation of PI3K gene and the components of the PI3K pathway themselves. Stimulation of the PI3K/Akt/mTOR and Ras/Raf/MEK/ERK pathways enhances growth, survival, and metabolism of cancer cells. Recently, the PI3K/Akt/mTOR and Ras/Raf/MEK/ERK signaling pathways have been identified as promising therapeutic targets for cancer therapy. The kinase inhibitors with enhanced specificity and improved pharmacokinetics have been considered for design and development of anticancer agents. This review focuses primarily on the Ras/Raf/MEK/ERK and PI3K/Akt/mTOR signaling pathways as therapeutic targets of anticancer drugs, their specific and dual inhibitors, structure activity relationships (SARs) and inhibitors under clinical trials.
authors.affiliation: Institute of Pharmaceutical Sciences, Guru Ghasidas Vishwavidyalaya (A Central University), Bilaspur 495009, Chhattisgarh, India.
authors.forename: Vivek
authors.initials: V
authors.lastname: Asati
authors.affiliation: Institute of Pharmaceutical Sciences, Guru Ghasidas Vishwavidyalaya (A Central University), Bilaspur 495009, Chhattisgarh, India.
authors.forename: Debarshi Kar
authors.initials: DK
authors.lastname: Mahapatra
authors.affiliation: Institute of Pharmaceutical Sciences, Guru Ghasidas Vishwavidyalaya (A Central University), Bilaspur 495009, Chhattisgarh, India. Electronic address: skbharti.ggu@gmail.com.
authors.forename: Sanjay Kumar
authors.initials: SK
authors.lastname: Bharti
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D055808:Drug Discovery; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D048490:raf Kinases / Q000378:metabolism; D018631:ras Proteins / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D048490:raf Kinases; D018631:ras Proteins; C546842:MTOR protein, human
keywords: Cancer; Inhibitors; PI3K; Ras; SAR; Signaling pathways