715
Views
30
CrossRef citations to date
0
Altmetric
Reviews

System-based drug discovery within the human kinome

Pages 1053-1070 | Published online: 13 Sep 2012

Bibliography

  • Manning G, Whyte DB, Martinez R, The protein kinase complement of the human genome. Science 2002;298(5600):1912-34
  • Weinmann H, Metternich R. Drug discovery process for kinase inhibitors. ChemBioChem 2005;6(3):455-9
  • Walker I, Newell H. Do molecularly targeted agents in oncology have reduced attrition rates? Nat Rev Drug Discov 2009;8(1):15-16
  • Fedorov O, Muller S, Knapp S. The (un)targeted cancer kinome. Nat Chem Biol 2010;6(3):166-9
  • World Intellectual Property Indicators. World Intellectual Property Organization. 2011. Avilable from www.wipo.int
  • LaMattina JL. The impact of mergers on pharmaceutical R&D. Nat Rev Drug Discov 2011;10(8):559-60
  • Pammolli F, Magazzini L, Riccaboni M. The productivity crisis in pharmaceutical R&D. Nat Rev Drug Discov 2011;10(6):428-38
  • Karaman MW, Herrgard S, Treiber DK, A quantitative analysis of kinase inhibitor selectivity. Nat Biotechnol 2008;26(1):127-32
  • Davies SP, Reddy H, Caivano M, Specificity and mechanism of action of some commonly used protein kinase inhibitors. Biochem J 2000;351(Pt 1):95-105
  • Jester BW, Gaj A, Shomin CD, Testing the Promiscuity of Commercial Kinase Inhibitors Against the AGC Kinase Group Using a Split-luciferase Screen. J Med Chem 2012;55(4):1526-37
  • Draft guidance for industry and food and drug administration staff - in vitro companion diagnostic devices. US Food and Drug Administration. 2011. Avilable from http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm262292.htm/
  • Schubert C. Cancer drugs find a companion with new diagnostic tests. Nat Med 2011;17(10):1157
  • Chiang A, Million RP. Personalized medicine in oncology: next generation. Nat Rev Drug Discov 2011;10(12):895-6
  • Barouch-Bentov R, Sauer K. Mechanisms of drug resistance in kinases. Expert Opin Investig Drugs 2011;20(2):153-208
  • Liegl B, Kepten I, Le C, Heterogeneity of kinase inhibitor resistance mechanisms in GIST. J Pathol 2008;216(1):64-74
  • Zhang Z, Stiegler AL, Boggon TJ, EGFR-mutated lung cancer: a paradigm of molecular oncology. Oncotarget 2010;1(7):497-514
  • Talpaz M, Shah NP, Kantarjian H, Dasatinib in imatinib-resistant Philadelphia chromosome-positive leukemias. N Engl J Med 2006;354(24):2531-41
  • Kantarjian H, Giles F, Wunderle L, Nilotinib in imatinib-resistant CML and Philadelphia chromosome-positive ALL. N Engl J Med 2006;354(24):2542-51
  • Mellinghoff IK, Wang MY, Vivanco I, Molecular determinants of the response of glioblastomas to EGFR kinase inhibitors. N Engl J Med 2005;353(19):2012-24
  • Stommel JM, Kimmelman AC, Ying H, Coactivation of receptor tyrosine kinases affects the response of tumor cells to targeted therapies. Science 2007;318(5848):287-90
  • Knight ZA, Lin H, Shokat KM. Targeting the cancer kinome through polypharmacology. Nat Rev Cancer 2010;10(2):130-7
  • Maira SM, Stauffer F, Schnell C, PI3K inhibitors for cancer treatment: where do we stand? Biochem Soc Trans 2009;37(Pt 1):265-72
  • Apsel B, Blair JA, Gonzalez B, Targeted polypharmacology: discovery of dual inhibitors of tyrosine and phosphoinositide kinases. Nat Chem Biol 2008;4(11):691-9
  • Sabbah DA, Brattain MG, Zhong H. Dual inhibitors of PI3K/mTOR or mTOR-selective inhibitors: which way shall we go? Curr Med Chem 2011;18(36):5528-44
  • Maira SM, Stauffer F, Brueggen J, Identification and characterization of NVP-BEZ235, a new orally available dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor with potent in vivo antitumor activity. Mol Cancer Ther 2008;7(7):1851-63
  • Chang KY, Tsai SY, Wu CM, Novel phosphoinositide 3-kinase/mTOR dual inhibitor, NVP-BGT226, displays potent growth-inhibitory activity against human head and neck cancer cells in vitro and in vivo. Clin Cancer Res 2011;17(22):7116-26
  • Cheng H, Bagrodia S, Bailey S, Discovery of the highly potent PI3K/mTOR dual inhibitor PF-04691502. MedChemComm 2010;1(1):139-44
  • Wallin JJ, Edgar KA, Guan J, GDC-0980 is a novel class I PI3K/mTOR kinase inhibitor with robust activity in cancer models driven by the PI3K pathway. Mol Cancer Ther 2011;10(12):2426-36
  • Muller S, Knapp S. Targeting kinases for the treatment of inflammatory diseases. Expert Opin Drug Discov 2010;5(9):867-81
  • Bamborough P, Drewry D, Harper G, Assessment of chemical coverage of kinome space and its implications for kinase drug discovery. J Med Chem 2008;51(24):7898-914
  • Wenlock MC, Austin RP, Barton P, A comparison of physiochemical property profiles of development and marketed oral drugs. J Med Chem 2003;46(7):1250-6
  • Gill AL, Verdonk M, Boyle RG, A comparison of physicochemical property profiles of marketed oral drugs and orally bioavailable anti-cancer protein kinase inhibitors in clinical development. Curr Top Med Chem 2007;7(14):1408-22
  • Waring MJ. Lipophilicity in drug discovery. Expert Opin Drug Discov 2010;5(3):235-48
  • Rusnak DW, Lackey K, Affleck K, The effects of the novel, reversible epidermal growth factor receptor/ErbB-2 tyrosine kinase inhibitor, GW2016, on the growth of human normal and tumor-derived cell lines in vitro and in vivo. Mol Cancer Ther 2001;1(2):85-94
  • Capdeville R, Buchdunger E, Zimmermann J, Glivec (STI571, imatinib), a rationally developed, targeted anticancer drug. Nat Rev Drug Discov 2002;1(7):493-502
  • Weisberg E, Manley PW, Breitenstein W, Characterization of AMN107, a selective inhibitor of native and mutant Bcr-Abl. Cancer Cell 2005;7(2):129-41
  • Wilhelm S, Carter C, Lynch M, Discovery and development of sorafenib: a multikinase inhibitor for treating cancer. Nat Rev Drug Discov 2006;5(10):835-44
  • Fejzo J, Lepre C, Xie X. Application of NMR screening in drug discovery. Curr Top Med Chem 2003;3(1):81-97
  • Hartshorn MJ, Murray CW, Cleasby A, Fragment-based lead discovery using X-ray crystallography. J Med Chem 2005;48(2):403-13
  • Erlanson DA. Introduction to fragment-based drug discovery. Top Curr Chem 2012;317:1-32
  • Bamborough P, Brown MJ, Christopher JA, Selectivity of kinase inhibitor fragments. J Med Chem 2011;54(14):5131-43
  • Goldstein DM, Kuglstatter A, Lou Y, Selective p38alpha inhibitors clinically evaluated for the treatment of chronic inflammatory disorders. J Med Chem 2010;53(6):2345-53
  • Genovese MC. Inhibition of p38: has the fat lady sung? Arthritis Rheum 2009;60(2):317-20
  • Damjanov N, Kauffman RS, Spencer-Green GT. Efficacy, pharmacodynamics, and safety of VX-702, a novel p38 MAPK inhibitor, in rheumatoid arthritis: results of two randomized, double-blind, placebo-controlled clinical studies. Arthritis Rheum 2009;60(5):1232-41
  • Cohen SB, Cheng TT, Chindalore V, Evaluation of the efficacy and safety of pamapimod, a p38 MAP kinase inhibitor, in a double-blind, methotrexate-controlled study of patients with active rheumatoid arthritis. Arthritis Rheum 2009;60(2):335-44
  • Genovese MC, Cohen SB, Wofsy D, A 24-week, randomized, double-blind, placebo-controlled, parallel group study of the efficacy of oral SCIO-469, a p38 mitogen-activated protein kinase inhibitor, in patients with active rheumatoid arthritis. J Rheumatol 2011;38(5):846-54
  • Tong SE, Daniels SE, Black P, Novel p38alpha Mitogen-Activated Protein Kinase Inhibitor Shows Analgesic Efficacy in Acute Postsurgical Dental Pain. J Clin Pharmacol 2012;52(5):717-28
  • O'Shea JJ, Plenge R. JAK and STAT signaling molecules in immunoregulation and immune-mediated disease. Immunity 2012;36(4):542-50
  • Garber K. Pfizer's JAK inhibitor sails through phase 3 in rheumatoid arthritis. Nat Biotechnol 2011;29(6):467-8
  • FDA Arthritis Advisory Committee Recommends Approval of Tofacitinib for Adult Patients with Moderately to Severely Active Rheumatoid Arthritis. Pfizer press release. 2012. Avilable from: http://www.pfizer.com/news/press_releases/pfizer_press_release.jsp?guid=20120509006571en&source=RSS_2011&page=1
  • Singh R, Masuda ES, Payan DG. Discovery and development of Spleen Tyrosine Kinase (SYK) inhibitors. J Med Chem 2012;55(8):3614-43
  • Bamborough P, Callahan JF, Christopher JA, Progress towards the development of anti-inflammatory inhibitors of IKKbeta. Curr Top Med Chem 2009;9(7):623-39
  • Schlapbach A, Huppertz C. Low-molecular-weight MK2 inhibitors: a tough nut to crack!. Future Med Chem 2009;1(7):1243-57
  • Zaytseva YY, Valentino JD, Gulhati P, mTOR inhibitors in cancer therapy. Cancer Lett 2012;319(1):1-7
  • Shuttleworth SJ, Silva FA, Cecil AR, Progress in the preclinical discovery and clinical development of class I and dual class I/IV phosphoinositide 3-kinase (PI3K) inhibitors. Curr Med Chem 2011;18(18):2686-714
  • Griffin JD. Interaction maps for kinase inhibitors. Nat Biotechnol 2005;23(3):308-9
  • Bi K, Lebakken CS, Vogel K. Transformation of in vitro tools for kinase profiling: keeping an eye over the off-target liabilities. Expert Opin Drug Discov 2011;6(7):701-12
  • Bain J, McLauchlan H, Elliott M, The specificities of protein kinase inhibitors: an update. Biochem J 2003;371(Pt 1):199-204
  • Bain J, Plater L, Elliott M, The selectivity of protein kinase inhibitors: a further update. Biochem J 2007;408(3):297-315
  • Fabian MA, Biggs WH III, Treiber DK, A small molecule-kinase interaction map for clinical kinase inhibitors. Nat Biotechnol 2005;23(3):329-36
  • Davis MI, Hunt JP, Herrgard S, Comprehensive analysis of kinase inhibitor selectivity. Nat Biotechnol 2011;29(11):1046-51
  • Posy SL, Hermsmeier MA, Vaccaro W, Trends in kinase selectivity: insights for target class-focused library screening. J Med Chem 2011;54(1):54-66
  • Anastassiadis T, Deacon SW, Devarajan K, Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity. Nat Biotechnol 2011;29(11):1039-45
  • Fedorov O, Marsden B, Pogacic V, A systematic interaction map of validated kinase inhibitors with Ser/Thr kinases. Proc Natl Acad Sci USA 2007;104(51):20523-8
  • Shakya T, Stogios PJ, Waglechner N, A small molecule discrimination map of the antibiotic resistance kinome. Chem Biol 2011;18(12):1591-601
  • Graczyk PP. Gini coefficient: a new way to express selectivity of kinase inhibitors against a family of kinases. J Med Chem 2007;50(23):5773-9
  • Uitdehaag JC, Zaman GJ. A theoretical entropy score as a single value to express inhibitor selectivity. BMC Bioinformatics 2011;12:94
  • Metz JT, Johnson EF, Soni NB, Navigating the kinome. Nat Chem Biol 2011;7(4):200-2
  • Frye SV. Structure-activity relationship homology (SARAH): a conceptual framework for drug discovery in the genomic era. Chem Biol 1999;6(1):R3-7
  • Vieth M, Higgs RE, Robertson DH, Kinomics-structural biology and chemogenomics of kinase inhibitors and targets. Biochim Biophys Acta 2004;1697(1-2):243-57
  • Force T, Kolaja KL. Cardiotoxicity of kinase inhibitors: the prediction and translation of preclinical models to clinical outcomes. Nat Rev Drug Discov 2011;10(2):111-26
  • Olaharski AJ, Gonzaludo N, Bitter H, Identification of a kinase profile that predicts chromosome damage induced by small molecule kinase inhibitors. PLoS Comput Biol 2009;5(7):e1000446
  • Olaharski AJ, Bitter H, Gonzaludo N, Modeling bone marrow toxicity using kinase structural motifs and the inhibition profiles of small molecular kinase inhibitors. Toxicol Sci 2010;118(1):266-75
  • Yang X, Huang Y, Crowson M, Kinase inhibition-related adverse events predicted from in vitro kinome and clinical trial data. J Biomed Inform 2010;43(3):376-84
  • Briggs K, Cases M, Heard DJ, Inroads to Predict in Vivo Toxicology-An Introduction to the eTOX Project. Int J Mol Sci 2012;13(3):3820-46
  • Zuercher B. The GSK published kinase inhibitor set: a resource for investigating the untargeted kinome. Presented at 2nd RSC Symposium on Chemical Biology for Drug Discovery; 20 – 21 March 2012; AstraZeneca, Alderley Park, Macclesfield, UK. Available from: http://www.maggichurchouseevents.co.uk/BMCS/2nd_RSC-CBDD.htm
  • Prinz F, Schlange T, Asadullah K. Believe it or not: how much can we rely on published data on potential drug targets? Nat Rev Drug Discov 2011;10(9):712
  • Coan KED, Ottl J, Klumpp M. Non-stoichiometric inhibition in biochemical high-throughput screening. Expert Opin Drug Discov 2011;6(4):405-17
  • McGovern SL, Shoichet BK. Kinase inhibitors: not just for kinases anymore. J Med Chem 2003;46(8):1478-83
  • Ryan AJ, Gray NM, Lowe PN, Effect of detergent on "promiscuous" inhibitors. J Med Chem 2003;46(16):3448-51
  • Huth JR, Mendoza R, Olejniczak ET, ALARM NMR: a rapid and robust experimental method to detect reactive false positives in biochemical screens. J Am Chem Soc 2005;127(1):217-24
  • Baell JB, Holloway GA. New substructure filters for removal of pan assay interference compounds (PAINS) from screening libraries and for their exclusion in bioassays. J Med Chem 2010;53(7):2719-40
  • Jadhav A, Ferreira RS, Klumpp C, Quantitative analyses of aggregation, autofluorescence, and reactivity artifacts in a screen for inhibitors of a thiol protease. J Med Chem 2010;53(1):37-51
  • Nadin A, Hattotuwagama C, Churcher I. Lead-oriented synthesis: a new opportunity for synthetic chemistry. Angew Chem Int Ed Engl 2012;51(5):1114-22
  • Oprea TI, Bologa CG, Boyer S, A crowdsourcing evaluation of the NIH chemical probes. Nat Chem Biol 2009;5(7):441-7
  • Bunnage ME. Getting pharmaceutical R&D back on target. Nat Chem Biol 2011;7(6):335-9
  • Vidalin O, Muslmani M, Estienne C, In vivo target validation using gene invalidation, RNA interference and protein functional knockout models: it is the time to combine. Curr Opin Pharmacol 2009;9(5):669-76
  • Hennig EE, Mikula M, Rubel T, Comparative kinome analysis to identify putative colon tumor biomarkers. J Mol Med (Berl) 2012;90(4):447-56
  • Johnson SA, Hunter T. Kinomics: methods for deciphering the kinome. Nat Methods 2005;2(1):17-25
  • Tiedemann RE, Zhu YX, Schmidt J, Kinome-wide RNAi studies in human multiple myeloma identify vulnerable kinase targets, including a lymphoid-restricted kinase. GRK6. Blood 2010;115(8):1594-604
  • Henderson MC, Gonzales IM, Arora S, High-throughput RNAi screening identifies a role for TNK1 in growth and survival of pancreatic cancer cells. Mol Cancer Res 2011;9(6):724-32
  • Giamas G, Filipovic A, Jacob J, Kinome screening for regulators of the estrogen receptor identifies LMTK3 as a new therapeutic target in breast cancer. Nat Med 2011;17(6):715-19
  • Choudhary S, Rosenblatt KP, Fang L, High throughput short interfering RNA (siRNA) screening of the human kinome identifies novel kinases controlling the canonical nuclear factor-kappaB (NF-kappaB) activation pathway. J Biol Chem 2011;286(43):37187-95
  • Morgan-Lappe S, Woods KW, Li Q, RNAi-based screening of the human kinome identifies Akt-cooperating kinases: a new approach to designing efficacious multitargeted kinase inhibitors. Oncogene 2006;25(9):1340-8
  • Horiuchi D, Huskey NE, Kusdra L, Chemical-genetic analysis of cyclin dependent kinase 2 function reveals an important role in cellular transformation by multiple oncogenic pathways. Proc Natl Acad Sci USA 2012;109(17):E1019-27
  • Urnov FD, Rebar EJ, Holmes MC, Genome editing with engineered zinc finger nucleases. Nat Rev Genet 2010;11(9):636-46
  • Lim ST, Chen XL, Tomar A, Knock-in mutation reveals an essential role for focal adhesion kinase activity in blood vessel morphogenesis and cell motility-polarity but not cell proliferation. J Biol Chem 2010;285(28):21526-36
  • Bishop AC, Shah K, Liu Y, Design of allele-specific inhibitors to probe protein kinase signaling. Curr Biol 1998;8(5):257-66
  • Garske AL, Peters U, Cortesi AT, Chemical genetic strategy for targeting protein kinases based on covalent complementarity. Proc Natl Acad Sci USA 2011;108(37):15046-52
  • Burkard ME, Jallepalli PV. Validating cancer drug targets through chemical genetics. Biochim Biophys Acta 2010;1806(2):251-7
  • Uitdehaag JC, Verkaar F, Alwan H, A guide to picking the most selective kinase inhibitor tool compounds for pharmacological validation of drug targets. Br J Pharmacol 2012;166(3):858-76
  • Frye SV. The art of the chemical probe. Nat Chem Biol 2010;6(3):159-61
  • Morphy R. Selectively nonselective kinase inhibition: striking the right balance. J Med Chem 2010;53(4):1413-37
  • Barnett SF, Defeo-Jones D, Fu S, Identification and characterization of pleckstrin-homology-domain-dependent and isoenzyme-specific Akt inhibitors. Biochem J 2005;385(Pt 2):399-408
  • Smith GK, Wood ER. Cell-based assays for kinase drug discovery. Drug Discovery Today: Technologies 2010;7(1):e13-19
  • Hancock MK, Lebakken CS, Wang J, Multi-pathway cellular analysis of compound selectivity. Mol Biosyst 2010;6(10):1834-43
  • Low J, Chakravartty A, Blosser W, Phenotypic fingerprinting of small molecule cell cycle kinase inhibitors for drug discovery. Curr Chem Genomics 2009;3:13-21
  • Swinney DC, Anthony J. How were new medicines discovered? Nat Rev Drug Discov 2011;10(7):507-19
  • Vogel KW, Zhong Z, Bi K, Developing assays for kinase drug discovery - where have the advances come from? Expert Opin Drug Discov 2008;3(1):115-29
  • Lee JA, Uhlik MT, Moxham CM, Modern Phenotypic Drug Discovery Is a Viable, Neoclassic Pharma Strategy. J Med Chem 2012;55(10):4527-38
  • Peters EC, Gray NS. Chemical proteomics identifies unanticipated targets of clinical kinase inhibitors. ACS Chem Biol 2007;2(10):661-4
  • Sleno L, Emili A. Proteomic methods for drug target discovery. Curr Opin Chem Biol 2008;12(1):46-54
  • Li J, Rix U, Fang B, A chemical and phosphoproteomic characterization of dasatinib action in lung cancer. Nat Chem Biol 2010;6(4):291-9
  • Bantscheff M, Eberhard D, Abraham Y, Quantitative chemical proteomics reveals mechanisms of action of clinical ABL kinase inhibitors. Nat Biotechnol 2007;25(9):1035-44
  • Li N, Overkleeft HS, Florea BI. Activity-based protein profiling: an enabling technology in chemical biology research. Curr Opin Chem Biol 2012;16(1-2):227-33
  • Patricelli MP, Nomanbhoy TK, Wu J, In situ kinase profiling reveals functionally relevant properties of native kinases. Chem Biol 2011;18(6):699-710
  • Lee JC, Laydon JT, McDonnell PC, A protein kinase involved in the regulation of inflammatory cytokine biosynthesis. Nature 1994;372(6508):739-46
  • ter Haar E, Walters WP, Pazhanisamy S, Kinase chemogenomics: targeting the human kinome for target validation and drug discovery. Mini Rev Med Chem 2004;4(3):235-53
  • Goldstein DM, Gray NS, Zarrinkar PP. High-throughput kinase profiling as a platform for drug discovery. Nat Rev Drug Discov 2008;7(5):391-7
  • Miduturu CV, Deng X, Kwiatkowski N, High-throughput kinase profiling: a more efficient approach toward the discovery of new kinase inhibitors. Chem Biol 2011;18(7):868-79
  • Reaume AG. Drug repurposing through nonhypothesis driven phenotypic screening. Drug Discovery Today: Therapeutic Strategies 2011;8(3-4):85-8
  • Nielsch U, Schafer S, Wild H, One target - multiple indications: a call for an integrated common mechanisms strategy. Drug Discov Today 2007;12(23-24):1025-31
  • GVK Bio. Available from: www.gvibio.com 2012
  • Southan C, Varkonyi P, Muresan S. Complementarity between public and commercial databases: new opportunities in medicinal chemistry informatics. Curr Top Med Chem 2007;7(15):1502-8
  • AurScope Kinase database, Aureus Pharma. Available from: http://www.aureus-pharma.com 2012
  • Benjamin D, Colombi M, Moroni C, Rapamycin passes the torch: a new generation of mTOR inhibitors. Nat Rev Drug Discov 2011;10(11):868-80
  • Moran N. p38 kinase inhibitor approved for idiopathic pulmonary fibrosis. Nat Biotechnol 2011;29(4):301
  • Intermune, Inc. Method of modulating stress-activated protein kinase system. WO2007062167; 2007
  • Hu-Lowe DD, Zou HY, Grazzini ML, Nonclinical antiangiogenesis and antitumor activities of axitinib (AG-013736), an oral, potent, and selective inhibitor of vascular endothelial growth factor receptor tyrosine kinases 1, 2, 3. Clin Cancer Res 2008;14(22):7272-83
  • Zou HY, Li Q, Lee JH, An orally available small-molecule inhibitor of c-Met, PF-2341066, exhibits cytoreductive antitumor efficacy through antiproliferative and antiangiogenic mechanisms. Cancer Res 2007;67(9):4408-17
  • Lombardo LJ, Lee FY, Chen P, Discovery of N-(2-chloro-6-methyl- phenyl)-2-(6-(4-(2-hydroxyethyl)- piperazin-1-yl)-2-methylpyrimidin-4- ylamino)thiazole-5-carboxamide (BMS-354825), a dual Src/Abl kinase inhibitor with potent antitumor activity in preclinical assays. J Med Chem 2004;47(27):6658-61
  • Moyer JD, Barbacci EG, Iwata KK, Induction of apoptosis and cell cycle arrest by CP-358,774, an inhibitor of epidermal growth factor receptor tyrosine kinase. Cancer Res 1997;57(21):4838-48
  • Wakeling AE, Guy SP, Woodburn JR, ZD1839 (Iressa): an orally active inhibitor of epidermal growth factor signaling with potential for cancer therapy. Cancer Res 2002;62(20):5749-54
  • Harris PA, Boloor A, Cheung M, Discovery of 5-[[4-[(2,3-dimethyl-2H-indazol-6-yl)methylamino]-2-pyrimidinyl]amino]-2-m ethyl-benzenesulfonamide (Pazopanib), a novel and potent vascular endothelial growth factor receptor inhibitor. J Med Chem 2008;51(15):4632-40
  • Quintas-Cardama A, Vaddi K, Liu P, Preclinical characterization of the selective JAK1/2 inhibitor INCB018424: therapeutic implications for the treatment of myeloproliferative neoplasms. Blood 2010;115(15):3109-17
  • Sun L, Liang C, Shirazian S, Discovery of 5-[5-fluoro-2-oxo-1,2- dihydroindol-(3Z)-ylidenemethyl]-2,4- dimethyl-1H-pyrrole-3-carboxylic acid (2-diethylaminoethyl)amide, a novel tyrosine kinase inhibitor targeting vascular endothelial and platelet-derived growth factor receptor tyrosine kinase. J Med Chem 2003;46(7):1116-19
  • Wedge SR, Ogilvie DJ, Dukes M, ZD6474 inhibits vascular endothelial growth factor signaling, angiogenesis, and tumor growth following oral administration. Cancer Res 2002;62(16):4645-55
  • Lee JT, Li L, Brafford PA, PLX4032, a potent inhibitor of the B-Raf V600E oncogene, selectively inhibits V600E-positive melanomas. Pigment Cell Melanoma Res 2010;23(6):820-7
  • Asano T, Ikegaki I, Satoh S, A protein kinase inhibitor, fasudil (AT-877): a novel approach to signal transduction therapy. Cardiovasc Drug Rev 1998;16(1):76-87
  • Hill RJ, Dabbagh K, Phippard D, Pamapimod, a novel p38 mitogen-activated protein kinase inhibitor: preclinical analysis of efficacy and selectivity. J Pharmacol Exp Ther 2008;327(3):610-19
  • Selness SR, Devraj RV, Devadas B, Discovery of PH-797804, a highly selective and potent inhibitor of p38 MAP kinase. Bioorg Med Chem Lett 2011;21(13):4066-71
  • Aston NM, Bamborough P, Buckton JB, p38alpha mitogen-activated protein kinase inhibitors: optimization of a series of biphenylamides to give a molecule suitable for clinical progression. J Med Chem 2009;52(20):6257-69
  • Singh D, Smyth L, Borrill Z, A randomized, placebo-controlled study of the effects of the p38 MAPK inhibitor SB-681323 on blood biomarkers of inflammation in COPD patients. J Clin Pharmacol 2010;50(1):94-100
  • Liu C, Lin J, Wrobleski ST, Discovery of 4-(5-(cyclopropylcarbamoyl)-2-methylphenylamino)-5-methyl-N-propylpyrrolo[1,2-f][ 1,2,4]triazine-6-carboxamide (BMS-582949), a clinical p38alpha MAP kinase inhibitor for the treatment of inflammatory diseases. J Med Chem 2010;53(18):6629-39
  • Flanagan ME, Blumenkopf TA, Brissette WH, Discovery of CP-690,550: a potent and selective Janus kinase (JAK) inhibitor for the treatment of autoimmune diseases and organ transplant rejection. J Med Chem 2010;53(24):8468-84

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.