title: MLN4924 therapy as a novel approach in cancer treatment modalities.
abstract: MLN4924 is an investigational and a newly discovered small molecule that is a potent and selective inhibitor of the NEDD8 (Neural precursor cell-Expressed Developmentally down-regulated 8) Activating Enzyme (NAE), a pivotal regulator of the Cullin Ring Ligases E3 (CRL), which has been implicated recently in DNA damage. MLN4924 effectively inhibits tumour cell growth by inducing all three common types of death, namely apoptosis, autophagy and senescence and it was also reported that the formation of capillary vessels was significantly suppressed by MLN4924.In this review, we are going to highlight the molecular mechanism of MLN4924 in cancer therapy and its pros and cons in cancer therapy.
authors: a Cellular & Molecular Biology Research Center, Medical Physics Department , Babol University of Medical Sciences , Iran.
authors: Maryam
authors: M
authors: Oladghaffari
authors: b Immonology Research Center , Tabriz University of Medical Sciences , Tabriz , Iran.|c Department of Medical Physics, Faculty of Medicine , Tabriz University of Medical Sciences , Tabriz , Iran.
authors: Jalil Pirayesh
authors: JP
authors: Islamian
authors: c Department of Medical Physics, Faculty of Medicine , Tabriz University of Medical Sciences , Tabriz , Iran.
authors: Behzad
authors: B
authors: Baradaran
authors: a Cellular & Molecular Biology Research Center, Medical Physics Department , Babol University of Medical Sciences , Iran.
authors: Ali Shabestani
authors: AS
authors: Monfared
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis; D001343:Autophagy; D018797:Cell Cycle Proteins / Q000378:metabolism; D044842:Cullin Proteins / Q000037:antagonists & inhibitors; D003517:Cyclopentanes / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D000072000:NF-KappaB Inhibitor alpha / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology / Q000627:therapeutic use*; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; C467199:CDT1 protein, human; D018797:Cell Cycle Proteins; D044842:Cullin Proteins; D003517:Cyclopentanes; C498702:PMAIP1 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D011743:Pyrimidines; D011838:Radiation-Sensitizing Agents; D000072000:NF-KappaB Inhibitor alpha; C539933:pevonedistat
keywords: Apoptosis; Cancer treatment; MLN4924; NEDD8 activating enzyme; UPS inhibitors (UPSI); Ubiquitin-proteasome system (UPS)