mitogen-activated protein kinase kinase kinase 5 | STE11 family | IUPHAR/BPS Guide to PHARMACOLOGY

来自 : 发布时间：2024-05-13

Annotated and awaiting review. Please contact us if you can help with reviewing. apoptosis signal regulating kinase 1|ASK1|MAPK/ERK kinase kinase 5|MAPKKK5|MEK kinase 5 Description: Crystal structure of human apoptosis signal-regulating kinase 1 (ASK1) with imidazopyridine inhibitor Download all structure-activity data for this target as a CSV file Description: Determined is aTR-FRET immunoassay, measuring phosphorylation of a biotinylated peptide substrate by ASK1 kinase. Description: Cellular assay; inhibition of ASK1-T838 autophosphorylation in HEK293T cells. EMD Millipore KinaseProfilerTM screen/Reaction Biology Kinase HotspotSM screen A screen profiling 158 kinase inhibitors (Calbiochem Protein Kinase Inhibitor Library I and II, catalogue numbers 539744 and 539745) for their inhibitory activity at 1 M and 10 M against 234 human recombinant kinases using the EMD Millipore KinaseProfilerTM service.A screen profiling the inhibitory activity of 178 commercially available kinase inhibitors at 0.5 M against a panel of 300 recombinant protein kinases using the Reaction Biology Corporation Kinase HotspotSM platform.http://www.millipore.com/techpublications/tech1/pf3036 http://www.reactionbiology.com/webapps/main/pages/kinase.aspx Physiological Consequences of Altering Gene Expression Ask1-/- mice have a normal phenotype and normal kidney structure and function. However, they exhibit dramatically reduced p38 MAPK activation and are protected from kidney injury in models of acute tubular necrosis and renal interstitial fibrosis. Apoptosis signal-regulating kinase 1 (ASK1, MAP3K5) is a stress-activated kinase. It is activated by cytotoxic stress factors such as TNF, Fas and reactive oxygen species (ROS), and once activated (autophosphorylated) it phosphorylates and activates downstream JNK and p38 MAP kinases which are responsible for the inflammatory and apoptotic stress responses [24]. ASK1 is an anti-fibrosis/anti-inflammatory drug target [6,17,20-21]. Modulation of ASK1 activity might also be relevant in the treatment of degenerative neurological disorders (MND [18], MS [9], Parkinson\'s disease [14], Alzheimer\'s disease [10] and ischemic stroke [4]) [11]. 1. Anastassiadis T, Deacon SW, Devarajan K, Ma H, Peterson JR.(2011)Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity. 2. Budas GR, Boehm M, Kojonazarov B, Viswanathan G, Tian X, Veeroju S, Novoyatleva T, Grimminger F, Hinojosa-Kirschenbaum F, Ghofrani HA et al..(2018)ASK1 Inhibition Halts Disease Progression in Preclinical Models of Pulmonary Arterial Hypertension. 3. Bunkoczi G, Salah E, Filippakopoulos P, Fedorov O, Müller S, Sobott F, Parker SA, Zhang H, Min W, Turk BE et al..(2007)Structural and functional characterization of the human protein kinase ASK1. 4. Cheon SY, Kim EJ, Kim SY, Kim JM, Kam EH, Park JK, Koo BN.(2018)Apoptosis Signal-regulating Kinase 1 Silencing on Astroglial Inflammasomes in an Experimental Model of Ischemic Stroke. 5. Davis MI, Hunt JP, Herrgard S, Ciceri P, Wodicka LM, Pallares G, Hocker M, Treiber DK, Zarrinkar PP.(2011)Comprehensive analysis of kinase inhibitor selectivity. 6. Furuichi K, Wada T, Iwata Y, Sakai N, Yoshimoto K, Kobayashi Ki K, Mukaida N, Matsushima K, Yokoyama H.(2002)Administration of FR167653, a new anti-inflammatory compound, prevents renal ischaemia/reperfusion injury in mice. 7. Gao Y, Davies SP, Augustin M, Woodward A, Patel UA, Kovelman R, Harvey KJ.(2013)A broad activity screen in support of a chemogenomic map for kinase signalling research and drug discovery. 8. Grynberg K, Ma FY, Nikolic-Paterson DJ.(2017)The JNK Signaling Pathway in Renal Fibrosis. 9. Guo X, Harada C, Namekata K, Matsuzawa A, Camps M, Ji H, Swinnen D, Jorand-Lebrun C, Muzerelle M, Vitte PA et al..(2010)Regulation of the severity of neuroinflammation and demyelination by TLR-ASK1-p38 pathway. 10. Hasegawa Y, Toyama K, Uekawa K, Ichijo H, Kim-Mitsuyama S.(2018)Role of ASK1/p38 Cascade in a Mouse Model of Alzheimer\'s Disease and Brain Aging. 11. Himmelbauer MK, Xin Z, Jones JH, Enyedy I, King K, Marcotte DJ, Murugan P, Santoro JC, Hesson T, Spilker K et al..(2019)Rational Design and Optimization of a Novel Class of Macrocyclic Apoptosis Signal-Regulating Kinase 1 Inhibitors. 12. Ichijo H, Nishida E, Irie K, ten Dijke P, Saitoh M, Moriguchi T, Takagi M, Matsumoto K, Miyazono K, Gotoh Y.(1997)Induction of apoptosis by ASK1, a mammalian MAPKKK that activates SAPK/JNK and p38 signaling pathways. 13. Lanier M, Pickens J, Bigi SV, Bradshaw-Pierce EL, Chambers A, Cheruvallath ZS, Cole D, Dougan DR, Ermolieff J, Gibson T et al..(2017)Structure-Based Design of ASK1 Inhibitors as Potential Agents for Heart Failure. 14. Lee KW, Woo JM, Im JY, Park ES, He L, Ichijo H, Junn E, Mouradian MM.(2015)Apoptosis signal-regulating kinase 1 modulates the phenotype of α-synuclein transgenic mice. 15. Liles JT, Corkey BK, Notte GT, Budas GR, Lansdon EB, Hinojosa-Kirschenbaum F, Badal SS, Lee M, Schultz BE, Wise S et al..(2018)ASK1 contributes to fibrosis and dysfunction in models of kidney disease. 16. Loomba R, Lawitz E, Mantry PS, Jayakumar S, Caldwell SH, Arnold H, Diehl AM, Djedjos CS, Han L, Myers RP et al..(2018)The ASK1 inhibitor selonsertib in patients with nonalcoholic steatohepatitis: A randomized, phase 2 trial. 17. Ma FY, Tesch GH, Nikolic-Paterson DJ.(2014)ASK1/p38 signaling in renal tubular epithelial cells promotes renal fibrosis in the mouse obstructed kidney. 18. Nishitoh H, Kadowaki H, Nagai A, Maruyama T, Yokota T, Fukutomi H, Noguchi T, Matsuzawa A, Takeda K, Ichijo H.(2008)ALS-linked mutant SOD1 induces ER stress- and ASK1-dependent motor neuron death by targeting Derlin-1. Patent number: US8742126 B2. Assignee: Gilead Sciences, Inc..Priority date: 27/01/2012. Publication date: 03/06/2014.20. Stambe C, Atkins RC, Tesch GH, Masaki T, Schreiner GF, Nikolic-Paterson DJ.(2004)The role of p38alpha mitogen-activated protein kinase activation in renal fibrosis. 21. Terada Y, Inoshita S, Kuwana H, Kobayashi T, Okado T, Ichijo H, Sasaki S.(2007)Important role of apoptosis signal-regulating kinase 1 in ischemic acute kidney injury. 22. Terao Y, Suzuki H, Yoshikawa M, Yashiro H, Takekawa S, Fujitani Y, Okada K, Inoue Y, Yamamoto Y, Nakagawa H et al..(2012)Design and biological evaluation of imidazo[1,2-a]pyridines as novel and potent ASK1 inhibitors. 23. Tesch GH, Ma FY, Han Y, Liles JT, Breckenridge DG, Nikolic-Paterson DJ.(2015)ASK1 Inhibitor Halts Progression of Diabetic Nephropathy in Nos3-Deficient Mice. 24. Tobiume K, Matsuzawa A, Takahashi T, Nishitoh H, Morita K, Takeda K, Minowa O, Miyazono K, Noda T, Ichijo H.(2001)ASK1 is required for sustained activations of JNK/p38 MAP kinases and apoptosis. 25. Wodicka LM, Ciceri P, Davis MI, Hunt JP, Floyd M, Salerno S, Hua XH, Ford JM, Armstrong RC, Zarrinkar PP et al..(2010)Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry. STE11 family: mitogen-activated protein kinase kinase kinase 5. Last modified on 30/01/2020. Accessed on 18/05/2020. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2080.