2p3g › Citations

Pyrrolopyridine inhibitors of mitogen-activated protein kinase-activated protein kinase 2 (MK-2).

Anderson DR, Meyers MJ, Vernier WF, Mahoney MW, Kurumbail RG, Caspers N, Poda GI, Schindler JF, Reitz DB, Mourey RJ
J Med Chem 50 2647-54 (2007)
Cited: 100 times
EuropePMC logo PMID: 17480064

Abstract

A new class of potent kinase inhibitors selective for mitogen-activated protein kinase-activated protein kinase 2 (MAPKAP-K2 or MK-2) for the treatment of rheumatoid arthritis has been prepared and evaluated. These inhibitors have IC50 values as low as 10 nM against the target and have good selectivity profiles against a number of kinases including CDK2, ERK, JNK, and p38. These MK-2 inhibitors have been shown to suppress TNFalpha production in U397 cells and to be efficacious in an acute inflammation model. The structure-activity relationships of this series, the selectivity for MK-2 and their activity in both in vitro and in vivo models are discussed. The observed selectivity is discussed with the aid of an MK-2/inhibitor crystal structure.

Reviews - 2p3g mentioned but not cited (1)

  1. Targeting Mitogen-Activated Protein Kinase-Activated Protein Kinase 2 (MAPKAPK2, MK2): Medicinal Chemistry Efforts To Lead Small Molecule Inhibitors to Clinical Trials. Fiore M, Forli S, Manetti F. J Med Chem 59 3609-3634 (2016)

Articles - 2p3g mentioned but not cited (8)

  1. Chemical Composition and Immunomodulatory Activity of Hypericum perforatum Essential Oils. Schepetkin IA, Özek G, Özek T, Kirpotina LN, Khlebnikov AI, Quinn MT. Biomolecules 10 E916 (2020)
  2. Binding affinity prediction for ligands and receptors forming tautomers and ionization species: inhibition of mitogen-activated protein kinase-activated protein kinase 2 (MK2). Natesan S, Subramaniam R, Bergeron C, Balaz S. J Med Chem 55 2035-2047 (2012)
  3. Chemical Composition and Immunomodulatory Activity of Essential Oils from Rhododendron albiflorum. Schepetkin IA, Özek G, Özek T, Kirpotina LN, Khlebnikov AI, Quinn MT. Molecules 26 3652 (2021)
  4. Prediction of specificity-determining residues for small-molecule kinase inhibitors. Caffrey DR, Lunney EA, Moshinsky DJ. BMC Bioinformatics 9 491 (2008)
  5. The crystal structure of the active form of the C-terminal kinase domain of mitogen- and stress-activated protein kinase 1. Malakhova M, D'Angelo I, Kim HG, Kurinov I, Bode AM, Dong Z. J Mol Biol 399 41-52 (2010)
  6. Volatile Composition, Antimicrobial Activity, and In Vitro Innate Immunomodulatory Activity of Echinacea purpurea (L.) Moench Essential Oils. Dosoky NS, Kirpotina LN, Schepetkin IA, Khlebnikov AI, Lisonbee BL, Black JL, Woolf H, Thurgood TL, Graf BL, Satyal P, Quinn MT. Molecules 28 7330 (2023)
  7. In silico insights into prediction and analysis of potential novel pyrrolopyridine analogs against human MAPKAPK-2: a new SAR-based hierarchical clustering approach. Konidala KK, Bommu UD, Yeguvapalli S, Pabbaraju N. 3 Biotech 8 385 (2018)
  8. Mechanism of Progesterone in Treatment of Traumatic Brain Injury Based on Network Pharmacology and Molecular Docking Technology. Zheng C, Gong J, Zang L, Song D, Ran X, Li J, Jiang B, Xu J, Wu Q. Med Sci Monit 28 e937564 (2022)


Reviews citing this publication (15)

  1. Heat shock protein 27 phosphorylation: kinases, phosphatases, functions and pathology. Kostenko S, Moens U. Cell Mol Life Sci 66 3289-3307 (2009)
  2. Targeting innate immunity protein kinase signalling in inflammation. Gaestel M, Kotlyarov A, Kracht M. Nat Rev Drug Discov 8 480-499 (2009)
  3. p38 pathway kinases as anti-inflammatory drug targets. Schindler JF, Monahan JB, Smith WG. J Dent Res 86 800-811 (2007)
  4. Targeting protein kinases for the development of anti-inflammatory drugs. Cohen P. Curr Opin Cell Biol 21 317-324 (2009)
  5. Heat shock protein 27 phosphorylation state is associated with cancer progression. Katsogiannou M, Andrieu C, Rocchi P. Front Genet 5 346 (2014)
  6. MAPKAPK2: the master regulator of RNA-binding proteins modulates transcript stability and tumor progression. Soni S, Anand P, Padwad YS. J Exp Clin Cancer Res 38 121 (2019)
  7. The role of p38 mitogen-activated protein kinase in the pathogenesis of inflammatory bowel disease. Feng YJ, Li YY. J Dig Dis 12 327-332 (2011)
  8. Non-kinase targets of protein kinase inhibitors. Munoz L. Nat Rev Drug Discov 16 424-440 (2017)
  9. MK2: a novel molecular target for anti-inflammatory therapy. Duraisamy S, Bajpai M, Bughani U, Dastidar SG, Ray A, Chopra P. Expert Opin Ther Targets 12 921-936 (2008)
  10. Mitogen-activated protein kinase-activated protein kinase 2 in neuroinflammation, heat shock protein 27 phosphorylation, and cell cycle: role and targeting. Gurgis FM, Ziaziaris W, Munoz L. Mol Pharmacol 85 345-356 (2014)
  11. Regulation of cytokines by small RNAs during skin inflammation. Bak RO, Mikkelsen JG. J Biomed Sci 17 53 (2010)
  12. Innate immune regulation of autoimmunity in multiple sclerosis: Focus on the role of Toll-like receptor 2. Hossain MJ, Hossain MJ, Hossain MJ, Tanasescu R, Gran B. J Neuroimmunol 304 11-20 (2017)
  13. Use of p38 MAPK Inhibitors for the Treatment of Werner Syndrome. Bagley MC, Davis T, Murziani PG, Widdowson CS, Kipling D. Pharmaceuticals (Basel) 3 1842-1872 (2010)
  14. Microtubule Depolymerization by Kinase Inhibitors: Unexpected Findings of Dual Inhibitors. Tanabe K. Int J Mol Sci 18 E2508 (2017)
  15. Fluorine-18: Radiochemistry and Target-Specific PET Molecular Probes Design. Wang Y, Lin Q, Shi H, Cheng D. Front Chem 10 884517 (2022)

Articles citing this publication (76)

  1. Kinase drug discovery--what's next in the field? Cohen P, Alessi DR. ACS Chem Biol 8 96-104 (2013)
  2. A Cdc7 kinase inhibitor restricts initiation of DNA replication and has antitumor activity. Montagnoli A, Valsasina B, Croci V, Menichincheri M, Rainoldi S, Marchesi V, Tibolla M, Tenca P, Brotherton D, Albanese C, Patton V, Alzani R, Ciavolella A, Sola F, Molinari A, Volpi D, Avanzi N, Fiorentini F, Cattoni M, Healy S, Ballinari D, Pesenti E, Isacchi A, Moll J, Bensimon A, Vanotti E, Santocanale C. Nat Chem Biol 4 357-365 (2008)
  3. Towards an integrated description of hydrogen bonding and dehydration: decreasing false positives in virtual screening with the HYDE scoring function. Reulecke I, Lange G, Albrecht J, Klein R, Rarey M. ChemMedChem 3 885-897 (2008)
  4. MAPK-activated protein kinase-2 in cardiac hypertrophy and cyclooxygenase-2 regulation in heart. Streicher JM, Ren S, Herschman H, Wang Y. Circ Res 106 1434-1443 (2010)
  5. Reactive oxygen species and p38 mitogen-activated protein kinase mediate tumor necrosis factor α-converting enzyme (TACE/ADAM-17) activation in primary human monocytes. Scott AJ, O'Dea KP, O'Callaghan D, Williams L, Dokpesi JO, Tatton L, Handy JM, Hogg PJ, Takata M. J Biol Chem 286 35466-35476 (2011)
  6. Suppression of the senescence-associated secretory phenotype (SASP) in human fibroblasts using small molecule inhibitors of p38 MAP kinase and MK2. Alimbetov D, Davis T, Brook AJ, Cox LS, Faragher RG, Nurgozhin T, Zhumadilov Z, Kipling D. Biogerontology 17 305-315 (2016)
  7. A benzothiophene inhibitor of mitogen-activated protein kinase-activated protein kinase 2 inhibits tumor necrosis factor alpha production and has oral anti-inflammatory efficacy in acute and chronic models of inflammation. Mourey RJ, Burnette BL, Brustkern SJ, Daniels JS, Hirsch JL, Hood WF, Meyers MJ, Mnich SJ, Pierce BS, Saabye MJ, Schindler JF, South SA, Webb EG, Zhang J, Anderson DR. J Pharmacol Exp Ther 333 797-807 (2010)
  8. A general and efficient method for the Suzuki-Miyaura coupling of 2-pyridyl nucleophiles. Billingsley KL, Buchwald SL. Angew Chem Int Ed Engl 47 4695-4698 (2008)
  9. Cigarette smoke and its component acrolein augment IL-8/CXCL8 mRNA stability via p38 MAPK/MK2 signaling in human pulmonary cells. Moretto N, Bertolini S, Iadicicco C, Marchini G, Kaur M, Volpi G, Patacchini R, Singh D, Facchinetti F. Am J Physiol Lung Cell Mol Physiol 303 L929-38 (2012)
  10. Nanoscale synthesis and affinity ranking. Gesmundo NJ, Sauvagnat B, Curran PJ, Richards MP, Andrews CL, Dandliker PJ, Cernak T. Nature 557 228-232 (2018)
  11. Novel tetrahydro-beta-carboline-1-carboxylic acids as inhibitors of mitogen activated protein kinase-activated protein kinase 2 (MK-2). Trujillo JI, Meyers MJ, Anderson DR, Hegde S, Mahoney MW, Vernier WF, Buchler IP, Wu KK, Yang S, Hartmann SJ, Reitz DB. Bioorg Med Chem Lett 17 4657-4663 (2007)
  12. Damage-induced DNA replication stalling relies on MAPK-activated protein kinase 2 activity. Köpper F, Bierwirth C, Schön M, Kunze M, Elvers I, Kranz D, Saini P, Menon MB, Walter D, Sørensen CS, Gaestel M, Helleday T, Schön MP, Dobbelstein M. Proc Natl Acad Sci U S A 110 16856-16861 (2013)
  13. MAPK-activated protein kinase 2 contributes to Clostridium difficile-associated inflammation. Bobo LD, El Feghaly RE, Chen YS, Dubberke ER, Han Z, Baker AH, Li J, Burnham CA, Haslam DB. Infect Immun 81 713-722 (2013)
  14. Phosphorylation of lysophosphatidylcholine acyltransferase 2 at Ser34 enhances platelet-activating factor production in endotoxin-stimulated macrophages. Morimoto R, Shindou H, Oda Y, Shimizu T. J Biol Chem 285 29857-29862 (2010)
  15. Pyrazinoindolone inhibitors of MAPKAP-K2. Goldberg DR, Choi Y, Cogan D, Corson M, DeLeon R, Gao A, Gruenbaum L, Hao MH, Joseph D, Kashem MA, Miller C, Moss N, Netherton MR, Pargellis CP, Pelletier J, Sellati R, Skow D, Torcellini C, Tseng YC, Wang J, Wasti R, Werneburg B, Wu JP, Xiong Z. Bioorg Med Chem Lett 18 938-941 (2008)
  16. Pyrrolo-pyrimidones: a novel class of MK2 inhibitors with potent cellular activity. Schlapbach A, Feifel R, Hawtin S, Heng R, Koch G, Moebitz H, Revesz L, Scheufler C, Velcicky J, Waelchli R, Huppertz C. Bioorg Med Chem Lett 18 6142-6146 (2008)
  17. Non-ionotropic NMDA receptor signaling gates bidirectional structural plasticity of dendritic spines. Stein IS, Park DK, Claiborne N, Zito K. Cell Rep 34 108664 (2021)
  18. The role of mitogen-activated protein kinase-activated protein kinase 2 in the p38/TNF-alpha pathway of systemic and cutaneous inflammation. Schottelius AJ, Zügel U, Döcke WD, Zollner TM, Röse L, Mengel A, Buchmann B, Becker A, Grütz G, Naundorf S, Friedrich A, Gaestel M, Asadullah K. J Invest Dermatol 130 481-491 (2010)
  19. p38MAPK/MK2-mediated phosphorylation of RBM7 regulates the human nuclear exosome targeting complex. Tiedje C, Lubas M, Tehrani M, Menon MB, Ronkina N, Rousseau S, Cohen P, Kotlyarov A, Gaestel M. RNA 21 262-278 (2015)
  20. Benzothiophene inhibitors of MK2. Part 1: structure-activity relationships, assessments of selectivity and cellular potency. Anderson DR, Meyers MJ, Kurumbail RG, Caspers N, Poda GI, Long SA, Pierce BS, Mahoney MW, Mourey RJ. Bioorg Med Chem Lett 19 4878-4881 (2009)
  21. Mesenchymal MAPKAPK2/HSP27 drives intestinal carcinogenesis. Henriques A, Koliaraki V, Kollias G. Proc Natl Acad Sci U S A 115 E5546-E5555 (2018)
  22. Synthesis and SAR studies of indole-based MK2 inhibitors. Xiong Z, Gao DA, Cogan DA, Goldberg DR, Hao MH, Moss N, Pack E, Pargellis C, Skow D, Trieselmann T, Werneburg B, White A. Bioorg Med Chem Lett 18 1994-1999 (2008)
  23. Benzothiophene inhibitors of MK2. Part 2: improvements in kinase selectivity and cell potency. Anderson DR, Meyers MJ, Kurumbail RG, Caspers N, Poda GI, Long SA, Pierce BS, Mahoney MW, Mourey RJ, Parikh MD. Bioorg Med Chem Lett 19 4882-4884 (2009)
  24. Novel 3-aminopyrazole inhibitors of MK-2 discovered by scaffold hopping strategy. Velcicky J, Feifel R, Hawtin S, Heng R, Huppertz C, Koch G, Kroemer M, Moebitz H, Revesz L, Scheufler C, Schlapbach A. Bioorg Med Chem Lett 20 1293-1297 (2010)
  25. Treatment with MAPKAP2 (MK2) inhibitor and DNA methylation inhibitor, 5-aza dC, synergistically triggers apoptosis in hepatocellular carcinoma (HCC) via tristetraprolin (TTP). Tran DDH, Koch A, Allister A, Saran S, Ewald F, Koch M, Nashan B, Tamura T. Cell Signal 28 1872-1880 (2016)
  26. Cell division cycle 7 is a novel regulator of transforming growth factor-β-induced smooth muscle cell differentiation. Shi N, Xie WB, Chen SY. J Biol Chem 287 6860-6867 (2012)
  27. Inhibition of the protein kinase MK-2 protects podocytes from nephrotic syndrome-related injury. Pengal R, Guess AJ, Agrawal S, Manley J, Ransom RF, Mourey RJ, Benndorf R, Smoyer WE. Am J Physiol Renal Physiol 301 F509-19 (2011)
  28. The potent Cdc7-Dbf4 (DDK) kinase inhibitor XL413 has limited activity in many cancer cell lines and discovery of potential new DDK inhibitor scaffolds. Sasi NK, Tiwari K, Soon FF, Bonte D, Wang T, Melcher K, Xu HE, Weinreich M. PLoS One 9 e113300 (2014)
  29. Viral activation of MK2-hsp27-p115RhoGEF-RhoA signaling axis causes cytoskeletal rearrangements, p-body disruption and ARE-mRNA stabilization. Corcoran JA, Johnston BP, McCormick C. PLoS Pathog 11 e1004597 (2015)
  30. Discovery of novel indolinone-based, potent, selective and brain penetrant inhibitors of LRRK2. Troxler T, Greenidge P, Zimmermann K, Desrayaud S, Drückes P, Schweizer T, Stauffer D, Rovelli G, Shimshek DR. Bioorg Med Chem Lett 23 4085-4090 (2013)
  31. Distinct roles of MK2 and MK5 in cAMP/PKA- and stress/p38MAPK-induced heat shock protein 27 phosphorylation. Shiryaev A, Dumitriu G, Moens U. J Mol Signal 6 4 (2011)
  32. High-resolution crystal structure of human Mapkap kinase 3 in complex with a high affinity ligand. Cheng R, Felicetti B, Palan S, Toogood-Johnson I, Scheich C, Barker J, Whittaker M, Hesterkamp T. Protein Sci 19 168-173 (2010)
  33. The MAPK-activated protein kinase 2 mediates gemcitabine sensitivity in pancreatic cancer cells. Köpper F, Binkowski AM, Bierwirth C, Dobbelstein M. Cell Cycle 13 884-889 (2014)
  34. Discovery and Hit-to-Lead Optimization of Non-ATP Competitive MK2 (MAPKAPK2) Inhibitors. Huang X, Shipps GW, Cheng CC, Spacciapoli P, Zhang X, McCoy MA, Wyss DF, Yang X, Achab A, Soucy K, Montavon DK, Murphy DM, Whitehurst CE. ACS Med Chem Lett 2 632-637 (2011)
  35. Mitogen-activated protein kinase-activated protein kinase 2 mediates resistance to hydrogen peroxide-induced oxidative stress in human hepatobiliary cancer cells. Nguyen Ho-Bouldoires TH, Clapéron A, Mergey M, Wendum D, Desbois-Mouthon C, Tahraoui S, Fartoux L, Chettouh H, Merabtene F, Scatton O, Gaestel M, Praz F, Housset C, Fouassier L. Free Radic Biol Med 89 34-46 (2015)
  36. Novel 1-(2-aminopyrazin-3-yl)methyl-2-thioureas as potent inhibitors of mitogen-activated protein kinase-activated protein kinase 2 (MK-2). Lin S, Lombardo M, Malkani S, Hale JJ, Mills SG, Chapman K, Thompson JE, Zhang WX, Wang R, Cubbon RM, O'Neill EA, Luell S, Carballo-Jane E, Yang L. Bioorg Med Chem Lett 19 3238-3242 (2009)
  37. Osmotic stress induces the phosphorylation of WNK4 Ser575 via the p38MAPK-MK pathway. Maruyama J, Kobayashi Y, Umeda T, Vandewalle A, Takeda K, Ichijo H, Naguro I. Sci Rep 6 18710 (2016)
  38. beta-Naphthoflavone analogs as potent and soluble aryl hydrocarbon receptor agonists: improvement of solubility by disruption of molecular planarity. Fujita Y, Yonehara M, Tetsuhashi M, Noguchi-Yachide T, Hashimoto Y, Ishikawa M. Bioorg Med Chem 18 1194-1203 (2010)
  39. Crucial roles of the protein kinases MK2 and MK3 in a mouse model of glomerulonephritis. Guess AJ, Ayoob R, Chanley M, Manley J, Cajaiba MM, Agrawal S, Pengal R, Pyle AL, Becknell B, Kopp JB, Ronkina N, Gaestel M, Benndorf R, Smoyer WE. PLoS One 8 e54239 (2013)
  40. NHC-Copper Mediated Ligand-Directed Radiofluorination of Aryl Halides. Sharninghausen LS, Brooks AF, Winton WP, Makaravage KJ, Scott PJH, Sanford MS. J Am Chem Soc 142 7362-7367 (2020)
  41. 2,4-Diaminopyrimidine MK2 inhibitors. Part II: Structure-based inhibitor optimization. Harris CM, Ericsson AM, Argiriadi MA, Barberis C, Borhani DW, Burchat A, Calderwood DJ, Cunha GA, Dixon RW, Frank KE, Johnson EF, Kamens J, Kwak S, Li B, Mullen KD, Perron DC, Wang L, Wishart N, Wu X, Zhang X, Zmetra TR, Talanian RV. Bioorg Med Chem Lett 20 334-337 (2010)
  42. Cytotoxic activity of the MK2 inhibitor CMPD1 in glioblastoma cells is independent of MK2. Gurgis F, Åkerfeldt MC, Heng B, Wong C, Adams S, Guillemin GJ, Johns TG, Chircop M, Munoz L. Cell Death Discov 1 15028 (2015)
  43. In vivo and in vitro SAR of tetracyclic MAPKAP-K2 (MK2) inhibitors. Part II. Revesz L, Schlapbach A, Aichholz R, Dawson J, Feifel R, Hawtin S, Littlewood-Evans A, Koch G, Kroemer M, Möbitz H, Scheufler C, Velcicky J, Huppertz C. Bioorg Med Chem Lett 20 4719-4723 (2010)
  44. MK2 signaling: lessons on tissue specificity in modulation of inflammation. Fyhrquist N, Matikainen S, Lauerma A. J Invest Dermatol 130 342-344 (2010)
  45. Direct ortho-arylation of N-phenacylpyridinium bromide by palladium-catalyzed C-H-bond activation. Xu J, Cheng G, Su D, Liu Y, Wang X, Hu Y. Chemistry 15 13105-13110 (2009)
  46. Discovery of selective and orally available spiro-3-piperidyl ATP-competitive MK2 inhibitors. Kaptein A, Oubrie A, de Zwart E, Hoogenboom N, de Wit J, van de Kar B, van Hoek M, Vogel G, de Kimpe V, Schultz-Fademrecht C, Borsboom J, van Zeeland M, Versteegh J, Kazemier B, de Roos J, Wijnands F, Dulos J, Jaeger M, Leandro-Garcia P, Barf T. Bioorg Med Chem Lett 21 3823-3827 (2011)
  47. Identification and SAR of squarate inhibitors of mitogen activated protein kinase-activated protein kinase 2 (MK-2). Lovering F, Kirincich S, Wang W, Combs K, Resnick L, Sabalski JE, Butera J, Liu J, Parris K, Telliez JB. Bioorg Med Chem 17 3342-3351 (2009)
  48. Structure-based lead identification of ATP-competitive MK2 inhibitors. Barf T, Kaptein A, de Wilde S, van der Heijden R, van Someren R, Demont D, Schultz-Fademrecht C, Versteegh J, van Zeeland M, Seegers N, Kazemier B, van de Kar B, van Hoek M, de Roos J, Klop H, Smeets R, Hofstra C, Hornberg J, Oubrie A. Bioorg Med Chem Lett 21 3818-3822 (2011)
  49. The MAP kinase-activated protein kinase 2 (MK2) contributes to the Shiga toxin-induced inflammatory response. Saenz JB, Li J, Haslam DB. Cell Microbiol 12 516-529 (2010)
  50. Novel ATP competitive MK2 inhibitors with potent biochemical and cell-based activity throughout the series. Oubrie A, Kaptein A, de Zwart E, Hoogenboom N, Goorden R, van de Kar B, van Hoek M, de Kimpe V, van der Heijden R, Borsboom J, Kazemier B, de Roos J, Scheffers M, Lommerse J, Schultz-Fademrecht C, Barf T. Bioorg Med Chem Lett 22 613-618 (2012)
  51. Rational mutagenesis to support structure-based drug design: MAPKAP kinase 2 as a case study. Argiriadi MA, Sousa S, Banach D, Marcotte D, Xiang T, Tomlinson MJ, Demers M, Harris C, Kwak S, Hardman J, Pietras M, Quinn L, DiMauro J, Ni B, Mankovich J, Borhani DW, Talanian RV, Sadhukhan R. BMC Struct Biol 9 16 (2009)
  52. The diterpenoid alkaloid noroxoaconitine is a Mapkap kinase 5 (MK5/PRAK) inhibitor. Kostenko S, Khan MT, Sylte I, Moens U. Cell Mol Life Sci 68 289-301 (2011)
  53. 2,4-Diaminopyrimidine MK2 inhibitors. Part I: Observation of an unexpected inhibitor binding mode. Argiriadi MA, Ericsson AM, Harris CM, Banach DL, Borhani DW, Calderwood DJ, Demers MD, Dimauro J, Dixon RW, Hardman J, Kwak S, Li B, Mankovich JA, Marcotte D, Mullen KD, Ni B, Pietras M, Sadhukhan R, Sousa S, Tomlinson MJ, Wang L, Xiang T, Talanian RV. Bioorg Med Chem Lett 20 330-333 (2010)
  54. Achieving multi-isoform PI3K inhibition in a series of substituted 3,4-dihydro-2H-benzo[1,4]oxazines. Perry B, Alexander R, Bennett G, Buckley G, Ceska T, Crabbe T, Dale V, Gowers L, Horsley H, James L, Jenkins K, Crépy K, Kulisa C, Lightfoot H, Lock C, Mack S, Morgan T, Nicolas AL, Pitt W, Sabin V, Wright S. Bioorg Med Chem Lett 18 4700-4704 (2008)
  55. In vivo and in vitro SAR of tetracyclic MAPKAP-K2 (MK2) inhibitors. Part I. Revesz L, Schlapbach A, Aichholz R, Feifel R, Hawtin S, Heng R, Hiestand P, Jahnke W, Koch G, Kroemer M, Möbitz H, Scheufler C, Velcicky J, Huppertz C. Bioorg Med Chem Lett 20 4715-4718 (2010)
  56. Mitogen-activated protein kinase-activated protein kinase-2 (MK2) and its role in cell survival, inflammatory signaling, and migration in promoting cancer. Morgan D, Berggren KL, Spiess CD, Smith HM, Tejwani A, Weir SJ, Lominska CE, Thomas SM, Gan GN. Mol Carcinog 61 173-199 (2022)
  57. The effect of small-molecule inhibition of MAPKAPK2 on cell ageing phenotypes of fibroblasts from human Werner syndrome. Davis T, Rokicki MJ, Bagley MC, Kipling D. Chem Cent J 7 18 (2013)
  58. Two additive mechanisms impair the differentiation of 'substrate-selective' p38 inhibitors from classical p38 inhibitors in vitro. Hendriks BS, Seidl KM, Chabot JR. BMC Syst Biol 4 23 (2010)
  59. A novel aminosaccharide compound blocks immune responses by Toll-like receptors and nucleotide-binding domain, leucine-rich repeat proteins. Lee KH, Liu YJ, Biswas A, Ogawa C, Kobayashi KS. J Biol Chem 286 5727-5735 (2011)
  60. Rank order entropy: why one metric is not enough. McLellan MR, Ryan MD, Breneman CM. J Chem Inf Model 51 2302-2319 (2011)
  61. Discovery and Optimization of Macrocyclic Quinoxaline-pyrrolo-dihydropiperidinones as Potent Pim-1/2 Kinase Inhibitors. Cee VJ, Chavez F, Herberich B, Lanman BA, Pettus LH, Reed AB, Wu B, Wurz RP, Andrews KL, Chen J, Hickman D, Laszlo J, Lee MR, Guerrero N, Mattson BK, Nguyen Y, Mohr C, Rex K, Sastri CE, Wang P, Wu Q, Wu T, Xu Y, Zhou Y, Winston JT, Lipford JR, Tasker AS, Wang HL. ACS Med Chem Lett 7 408-412 (2016)
  62. A computational study on thiourea analogs as potent MK-2 inhibitors. Hao M, Ren H, Luo F, Zhang S, Qiu J, Ji M, Si H, Li G. Int J Mol Sci 13 7057-7079 (2012)
  63. Assessment of the putative binding conformation of a pyrazolopyridine class of inhibitors of MAPKAPK2 using computational studies. Miglani R, Cliffe IA, Voleti SR. Eur J Med Chem 45 98-105 (2010)
  64. Comparative molecular dynamics simulations of mitogen-activated protein kinase-activated protein kinase 5. Lindin I, Wuxiuer Y, Ravna AW, Moens U, Sylte I. Int J Mol Sci 15 4878-4902 (2014)
  65. Discovery of a Potent Dihydrooxadiazole Series of Non-ATP-Competitive MK2 (MAPKAPK2) Inhibitors. Qin J, Dhondi P, Huang X, Aslanian R, Fossetta J, Tian F, Lundell D, Palani A. ACS Med Chem Lett 3 100-105 (2012)
  66. Microwave-Assisted Synthesis of a MK2 Inhibitor by Suzuki-Miyaura Coupling for Study in Werner Syndrome Cells. Bagley MC, Baashen M, Chuckowree I, Dwyer JE, Kipling D, Davis T. Pharmaceuticals (Basel) 8 257-276 (2015)
  67. Structural analysis of an MK2-inhibitor complex: insight into the regulation of the secondary structure of the Gly-rich loop by TEI-I01800. Fujino A, Fukushima K, Namiki N, Kosugi T, Takimoto-Kamimura M. Acta Crystallogr D Biol Crystallogr 66 80-87 (2010)
  68. A general direct arylation of polyfluoroarenes with heteroaryl and aryl chlorides catalyzed by palladium indolylphosphine complexes. Yuen OY, Charoensak M, So CM, Kuhakarn C, Kwong FY. Chem Asian J 10 857-861 (2015)
  69. Deciphering the true antiproliferative target of an MK2 activation inhibitor in glioblastoma. Brennan PE. Cell Death Dis 7 e2069 (2016)
  70. Design, Synthesis and Biological Evaluation of Arylpyridin-2-yl Guanidine Derivatives and Cyclic Mimetics as Novel MSK1 Inhibitors. An Application in an Asthma Model. Bollenbach M, Nemska S, Wagner P, Camelin G, Daubeuf F, Obrecht A, Villa P, Rognan D, Bihel F, Bourguignon JJ, Schmitt M, Frossard N. Molecules 26 E391 (2021)
  71. Ammonium Acetate-Promoted One-Pot Tandem Aldol Condensation/Aza-Addition Reactions: Synthesis of 2,3,6,7-Tetrahydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-ones. Zhang Z, Gao X, Wan Y, Huang Y, Huang G, Zhang G. ACS Omega 2 6844-6851 (2017)
  72. Nijmegen breakage syndrome fibroblasts expressing the C-terminal truncated NBN(p70) protein undergo p38/MK2-dependent premature senescence. Davis T, Tivey HS, Brook AJ, Kipling D. Biogerontology 16 43-51 (2015)
  73. Selective Inhibition of the MK2 Pathway: Data From a Phase IIa Randomized Clinical Trial in Rheumatoid Arthritis. Gordon D, Kivitz A, Singhal A, Burt D, Bangs MC, Huff EE, Hope HR, Monahan JB. ACR Open Rheumatol 5 63-70 (2023)
  74. Prediction of kinase-inhibitor binding affinity using energetic parameters. Usha S, Selvaraj S. Bioinformation 12 172-181 (2016)
  75. Regulation of CCR4-NOT complex deadenylase activity and cellular responses by MK2-dependent phosphorylation of CNOT2. Suzuki T, Hoshina M, Nishijima S, Hoshina N, Kikuguchi C, Tomohiro T, Fukao A, Fujiwara T, Yamamoto T. RNA Biol 19 234-246 (2022)
  76. Small molecule targeting of the p38/Mk2 stress signaling pathways to improve cancer treatment. Alimbetov D, Umbayev B, Tsoy A, Begimbetova D, Davis T, Kipling D, Askarova S. BMC Cancer 23 895 (2023)


Quick links