Drug design of Src Kinase inhibitor: An overview
DOI:
https://doi.org/10.56511/JIPBS.2018.v5.i01.pp51-59Abstract
Drug discovery for chemotherapeutic agent is making an extraordinary progress in the realm of advancing novel oncogenic protein kinase inhibitor lead compounds of varying chemical structure and biological mechanism. In the last 40 years, the first protein kinase, pp60src(Src), was discovered as a prototype of the new current superfamily of Ser/Thr, Tyr and dual-specificity protein kinases. In this review, we will highlight Src kinase inhibitors with respect to the structural biology, drug design, chemical diversity, and biological properties. This will help medicinal chemist to the design of more potent Src kinase inhibitors for resistive target protein in cancer
Keywords:
Drug discovery, Src Kinase inhibitors, BMS-354825Downloads
References
Vieth M, Higgs RE, Robertson DH, Shapiro M, Gragg EA, Hemmerle H. Kinomics-structural biology and chemogenomics of kinase inhibitors and targets. Biochim Biophys Acta 2004; 1697:243 – 257.
Cherry M, Williams DH. Recent kinase and kinase inhibitor X-ray structures: mechanisms of inhibition and selectivity insights. Curr Med Chem 2004; 11:663 – 673.
Muegge I, Enyedy IJ. Virtual screening for kinase targets. Curr Med Chem 2004; 11:693 – 707.
Dancey J, Sausville EA. Issues and progress with protein kinase inhibitors for cancer treatment. Nat Rev Drug Discov 2003; 2:296 – 313.
Drevs J, Medinger M, Schmidt – Gersbach C, Weber R, Unger C. Receptor tyrosine kinases: the main targets for new anticancer therapy. Curr Drug Targets 2003; 4:113 – 121.
Diller DJ, Li R. Kinases, homology models, and high throughput docking. J Med Chem 2003; 46:4638 – 4647.
Sawyer TK, Shakespeare WC, Wang Y, Sundaramoorthi R, Huang WS, Metcalf CA, Thomas M, Lawrence BM, Rozamus L, Noehre J, Zhu X, Narula S, Bohacek RS, Weigele M, Dalgarno DC. Protein phosphorylation and signal transduction modulation: chemistry perspectives for small-molecule drug discovery. Med Chem 2005; 1:293 – 319.
Laird AD, Cherrington JM. Small molecule tyrosine kinase inhibitors: clinical development of anticancer agents. Exp Opin Inv Drug 2003; 12:51 – 64.
Nam N-H, Paranga K, Current targets for anticancer drug discovery .Curr Drug Targets 2003; 4:159 – 179.
Blume-Jensen P, Hunter T. Oncogenic kinase signalling. Nature 2002; 411:355 – 365.
Cohen P. Protein kinases--the major drug targets of the twenty-first century?. Nat Rev Drug Disc 2002; 1:309 – 315.
FabbroD, Ruetz S, Buchdunger E, Cowan-Jacob SW, FendrichG, Liebetanz J, MestanJ, O’ReillyT, TraxlerP, Chaudhuri B, FretzH, ZimmermannJ, MeyerT, CaravattiG, Furet P, Manley PW Protein kinases as targets for anticancer agents: from inhibitors to useful drugs. Pharmacol Ther 2002; 93:79 – 98.
Brunelleschi S, Penego L, Santoro MM, Gaudino. G Receptor tyrosine kinases as target for anti-cancer therapy. Curr Pharm Des 2002; 8:1959 – 1972.
Scapin G. Structural biology in drug design: selective protein kinase inhibitors. Drug Disc Today 2002; 11:601 – 611.
Huse M, Kuriyan J. The conformational plasticity of protein kinases. Cell 2002; 109:275 – 282.
Naumann T, Matter H. Structural classification of protein kinases using 3D molecular interaction field analysis of their ligand binding sites: target family landscapes. J Med Chem 2002; 45:2366 – 2378.
Woolfrey JR, Weston GS. The use of computational methods in the discovery and design of kinase inhibitors. Curr Pharm Des 2002; 8:1527 – 1545.
Bridges AJ. Chemical inhibitors of protein kinases. Chem Rev 2001; 101:2541 – 2572.
Dumas J. Protein kinase inhibitors: emerging pharmacophores 1997 – 2000. Exp Opin Ther Pat 2005; 11:405 – 429.
Tsatsanis C, Spandidos DA. The role of oncogenic kinases in human cancer (Review). Int J Mol Med 2000; 5:583 – 590.
De Jong MJ, Verweij J. Multiple targeted tyrosine kinase inhibition in the clinic: all for one or one for all?. Eur J Cancer 2006; 42:1351 – 1356.
Mikalsen T, Gerits N, Moens U. Inhibitors of signal transduction protein kinases as targets for cancer therapy. Biotechnol Annu Rev 2006; 12:153 – 223.
Ventura JJ, Nebreda AR. Protein kinases and phosphatases as therapeutic targets in cancer. Clin Transl Oncol 2006; 8:153 – 160.
Sawyer TK. Novel oncogenic protein kinase inhibitors for cancer therapy. Curr Med Chem Anticancer Agents 2004; 4:449 – 455.
Becker J. Signal transduction inhibitors--a work in progress. Nat Biotechnol 2004; 22:15 – 18.
Thomas SM, Brugge JS. Cellular functions regulated by Src family kinases. Annu Rev Cell Dev Biol 1997; 13:513 – 609.
Manning G, Whyte DB, Marrtinez R, Hunter T, Sudarasanam S. The protein kinase complement of the human genome. Science 2002; 298:1912 – 1934.
Xu W, Harrison SC, Eck MJ. Three-dimensional structure of the tyrosine kinase c-Src. Nature 1997; 285:595 – 602.
Williams JC, Weijland A, Gonfloni S, Thomson A, Courtneidge SA, Superti-FurgaG, Wierenga RK. The 2.35 A crystal structure of the inactivated form of chicken Src: a dynamic molecule with multiple regulatory interactions. J Mol Biol 1997; 274:757 – 775.
Xu W, Doshi A, Lei M, Eck M, Harrison SC. Crystal structures of c-Src reveal features of its autoinhibitory mechanism. Mol Cell 1999; 3:629 – 636.
Dalgarno D, Stehle T, Narula S, Schelling P, van Schravendijk MR, Adams S, Andrade L, Keats J, Ram M, Jin L, Grossman T, MacNeil I, Metcalf C, ShakespeareW, Wang Y, Keenan T, Sundaramoorthi R, Bohacek R, Weigele M, Sawyer T. Structural basis of Src tyrosine kinase inhibition with a new class of potent and selective trisubstituted purinebased compounds. Chem Biol Drug Des 2006; 67:46 – 57.
Breitenlechner CB, Kairies NA, Honold K, Scheiblich S, Koll H, Greiter E, Koch S, Schafer W, Huber R, Engh RA. Crystal structures of active SRC kinase domain complexes. J Mol Biol 2005; 353:222 – 231.
WarmuthM, Damoiseaux R, Liu Y, Fabbro D, Gray N. SRC family kinases: potential targets for the treatment of human cancer and leukemia. Curr Pharm Des 2004; 9:2043 – 2059.
Sawyer T, Boyce B, Dalgarno D, Iuliucci J. Src inhibitors: genomics to therapeutics. Exp Opin Inv Drug 2001; 10:1327 – 1344.
Susa M, Missbach M, Green J. Src inhibitors: drugs for the treatment of osteoporosis, cancer or both?. Trends Pharmacol Sci 2000; 21:489 – 495.
Cowan-Jacob SW, Fendrich G, Manley PW, Jahnke W, Fabbro D, Liebetanz J, Meyer T. The crystal structure of a c-Src complex in an active conformation suggests possible steps in c-Src activation. Structure 2005; 13:861 – 871.
Sawyer TK, Wang Y, Shakespeare WC, Metcalf CA, Sundaramoorthi R, Narula S, Dalgarno DC. In: Waksman G (ed) Proteomics and protein – protein interactions: biology chemistry bioinformatics and drug design series: protein reviews. Springer, Berlin Heidelberg New York, 2005; 3:219 – 253.
Metcalf CA III, van Schravendijk MR, Dalgarno DC, Sawyer TK.Targeting protein kinases for bone disease: discovery and development of Src inhibitors. Curr Pharm Design 2002; 8:2049 – 2075.
Shakespeare WC, Metcalf CA III, Wang Y, Sundaramoorthi R, Keenan T, Weigele M, Bohacek RS, Dalgarno DC, Sawyer TK. Novel bone-targeted Src tyrosine kinase inhibitor drug discovery. Curr Opin Drug Disc Dev 2003; 6:729 – 741.
Trevino JG, Summy JM, Gallick GE. SRC inhibitors as potential therapeutic agents for human cancers. Mini Rev Med Chem 2006; 6:681 – 687.
Shah NP, Tran C, Lee FY, Chen P, Norris D, Sawyers CL. Overriding imatinib resistance with a novel ABL kinase inhibitor. Science 2004; 305:399 – 401.
LombardoLJ, LeeFY, ChenP, NorrisD, BarrishJC, BehniaK, CastanedaS, Cornelius LAM, Das J, Doweyko AM, Fairchild C, Hunt JT, Inigo I, Johnston K, Kamath A, Kan D, Klei H, Marathe P, Pang S, Peterson R, Pitt S, Schieven GL, Schmidt RJ, Tokarski J, Wen M-L, Wityak J, Borzilleri RM. Discovery of N-(2-chloro-6-methylphenyl)-2-(6-(4-(2hydroxyethyl)- piperazin-1-yl)-2-methylpyrimidin-4ylamino)thiazole-5carboxamide (BMS-354825), a dual Src/Abl kinase inhibitor with potent antitumor activity in preclinical assays. J Med Chem 2004; 47:6658 – 6661.
Burgess MR, Skaggs BJ, Shah NP, Lee FY, Sawyers CL. Comparative analysis of two clinically active BCR-ABL kinase inhibitors reveals the role of conformation-specific binding in resistance. Proc Natl Acad Sci USA 2005; 102:3395 – 3400.
Trevino JG, Summy JM, Lesslie DP, Parikh NU, Hong DS, Lee FY, Donato NJ, Abbruzzese JL, Baker CH, Gallick GE. Inhibition of SRC expression and activity inhibits tumor progression and metastasis of human pancreatic adenocarcinoma cells in an orthotopic nude mouse model. Am J Pathol 2006; 168:962 – 972.
Johnson FM, Saigal B, Talpaz M, Donato NJ. Dasatinib (BMS-354825) tyrosine kinase inhibitor suppresses invasion and induces cell cycle arrest and apoptosis of head and neck squamous cell carcinoma and non-small cell lung cancer cells. Clin Cancer Res 2005; 11:6924 – 6932.
NamS, KimD, Cheng JQ, Zhang S, Lee JH, Buettner R, Mirosevich J, Lee FY, JoveR. Action of the Src family kinase inhibitor, dasatinib (BMS354825), on human prostate cancer cells. Cancer Res 2005; 65:9185 – 9189.
Appel CK , Gallego-Pedersen S, Andersen L, Blancheflor Kristensen S, Ding M, Falk S, Sayilekshmy M, Gabel-Jensen C, Heegaard AM. The Src family kinase inhibitor dasatinib delays pain-related behaviour and conserves bone in a rat model of cancer-induced bone pain. Sci Rep 2017; 1:4792.
Wang YD, Miller K, Boschelli DH, Ye F, Wu B, Floyd MB, Powell DW, Wissner A, Weber JM, Boschelli F. Inhibitors of src tyrosine kinase: the preparation and structure-activity relationship of 4-anilino-3cyanoquinolines and 4-anilinoquinazolines. Bioorg Med Chem Lett 2000; 10:2477 – 2480.
Dorsey JF, Jove R, Kraker AJ, Wu J. The pyrido[2,3-d]pyrimidine derivative PD180970 inhibits p210Bcr-Abl tyrosine kinase and induces apoptosis of K562 leukemic cells. Cancer Res 2000; 60:3127 – 3131.
Huang M, Dorsey JF, Epling-Burnette PK, Nimmanapalli R, Landowski TH, Mora LB, NiuG, SinibaldiD, BaiF, KrakerA, YuH, Moscinski L, Wei S, DjeuJ, DaltonWS, Bhalla K, Loughran TP, Wu J, Jove R . Inhibition of Bcr-Abl kinase activity by PD180970 blocks constitutive activation of Stat5 and growth of CML cells. Oncogene 2002; 21:8804 – 8816.
La Rosee P, Corbin AS, Stoffregen EP, Deininger MW, Druker BJ. Activity of the Bcr-Abl kinase inhibitor PD180970 against clinically relevant Bcr-Abl isoforms that cause resistance to imatinib mesylate (Gleevec, STI571). Cancer Res 2002; 62:7149 – 7173.
Hamby JM, Connolly CJ, Schroeder MC, Winters RT, Showalter HD, Panek RL, Major TC, OlsewskiB, RyanMJ, Dahring T, LuGH, Keiser J, AmarA, Shen C, KrakerAJ, Slintak V, Nelson JM, Fry DW, Bradford L, Hallak H, Doherty AM.Structure-activity relationships for a novel series of pyrido[2,3-d]pyrimidine tyrosine kinase inhibitors. J Med Chem 1997; 40:2296 – 2303.
KlutchkoSR, HambyJM, BoschelliDH, WuZ, KrakerAJ, AmarAM, HartlBG, Shen C, KlohsWD, Steinkampf RW, Driscoll DL, Nelson JM, ElliottWL, Roberts BJ, StonerCL, Vincent PW, DykesDJ, PanekRL, LuGH, MajorTC, DahringTK, HallakH, Bradford LA, Showalter HD, Doherty AM. 2-Substituted Aminopyrido[2,3-d]pyrimidin-7(8H)-ones. Structure−Activity Relationships against Selected Tyrosine Kinases and in Vitro and in Vivo Anticancer Activity. J Med Chem 1998; 41:3276 – 3292.
Kraker AJ, Hartl BG, Amar AM, Barvian MR, Showalter HD, Moore CW. Biochemical and cellular effects of c-Src kinase-selective pyrido[2, 3-d]pyrimidine tyrosine kinase inhibitors. Biochem Pharmacol 2000; 60:885 – 898.
Wisniewski D, Lambek CL, Liu C, Strife A, Veach DR, Nagar B, Young MA, Schindler T, Bornmann WG, Bertino JR, Kuriyan J, Clarkson B. Characterization of potent inhibitors of the Bcr-Abl and the c-kit receptor tyrosine kinases. Cancer Res 2002; 62:4244 – 4255.
Nimmanapalli R, O ’ Bryan E, Huang M, Bali P, Burnette PK, Loughran T, TepperbergJ, Jove R, Bhalla K. Molecular characterization and sensitivity of STI-571 (imatinib mesylate, Gleevec)-resistant, Bcr-Abl-positive, human acute leukemia cells to SRC kinase inhibitor PD180970 and 17allylamino-17-demethoxygeldanamycin. Cancer Res 2002; 62:5761 – 5769.
Wolff NC, Veach DR, Tong WP, BornmannWG, Clarkson B, Ilaria RL Jr.PD166326, a novel tyrosine kinase inhibitor, has greater antileukemic activity than imatinib mesylate in a murine model of chronic myeloid leukemia. Blood 2005; 105:3995 – 4003.
Moasser MM, Srethapakdi M, Sachar KS, Kraker AJ, Rosen N. Inhibition of Src kinases by a selective tyrosine kinase inhibitor causes mitotic arrest. Cancer Res 1999; 59:6145 – 6152.
You L, Liu H, Huang J, Xie W, Wei J, Ye X, Qian W. The novel anticancer agent JNJ-26854165 is active in chronic myeloid leukemic cells with unmutated BCR/ABL and T315I mutant BCR/ABL through promoting proteosomal degradation of BCR/ABL proteins. Oncotarget 2017; 5:7777-7790.
Hanke JH, Gardner JP, Dow RL, Changelian PS, Brissette WH, Weringer EJ, Pollok BA, Connelly PA . Discovery of a novel, potent, and Src family-selective tyrosine kinase inhibitor. Study of Lckand FynTdependent T cell activation. J Biol Chem 1996; 271:695 – 701.
Eliceiri BP, Paul R, Schwartzbert PI, Hood JD, Leng J, Cheresch DA. Selective requirement for Src kinases during VEGF-induced angiogenesis and vascular permeability. J Mol Cell 1999; 4:915 – 924.
Paul R, Zhang ZG, Eliceiri BP, Jiang Q, Boccia AD, Zhang RL, Chopp M, Cheresh DA. Src deficiency or blockade of Src activity in mice provides cerebral protection following stroke. Nat Med 2001; 7:222 – 227.
Belsches-Jablonski AP, Biscardi JS, Peavy DR, Tice DA, Romney DA, Parsons SJ. Src family kinases and HER2 interactions in human breast cancer cell growth and survival. Oncogene 2000; 20:1464 – 1475.
Menke A, Philipp C, Vogelmann R, Seidel B, LutzMP, Adler G, Wedlich D. Down-regulation of E-cadherin gene expression by collagen type I and type III in pancreatic cancer cell lines. Cancer Res 2001; 61:3508 – 3517.
Tatton L, Morley GM, Chopras R, Khwaja A .The Src-selective Kinase Inhibitor PP1 Also Inhibits Kit and Bcr-Abl Tyrosine Kinases. J Biol Chem 2003; 278:4847 – 4853.
Warmuth M, Simon N, Mitina O, Mathes R, Fabbro D, Manley PW, Buchdunger E,Forster K, Moarefi I, Hallek M .The Src-selective kinase inhibitor PP1 also inhibits Kit and Bcr-Abl tyrosine kinases. Blood 2003; 101:664 – 672.
Wilson MB, Schreiner SJ, Choi H-J, Kamens J, Smithgall TS. Selective pyrrolo-pyrimidine inhibitors reveal a necessary role for Src family kinases in Bcr-Abl signal transduction and oncogenesis. Oncogene 2002; 21:8075 – 8088.
Tatton L, Morley GM, Chopra R, Khwaja A. The Src-selective kinase inhibitor PP1 also inhibits Kit and Bcr-Abl tyrosine kinases. J Biol Chem 2003; 278:4847 – 4853.
Warmuth M, Simon N, Mitina O, Mathes R, Fabbro D, Manley PW, Buchdunger E,Forster K, Moarefi I, Hallek M. Dual-specific Src and Abl kinase inhibitors, PP1 and CGP76030, inhibit growth and survival of cells expressing imatinib mesylate-resistant Bcr-Abl kinases. Blood 2003; 101:664 – 672.
Gilmore ES, Stutts MJ, Milgram SL. SRC family kinases mediate epithelial Na+ channel inhibition by endothelin. J Biol Chem; 2001, 276:42610 – 42617 15.
Klinger M, Kudlacek O, Seidel MG, Freissmuth M, Sexl V. MAP kinase stimulation by cAMP does not require RAP1 but SRC family kinases. J Biol Chem 2002;2 77:32490 – 32497.
Kong L, Deng Z, Shen H, Zhang Y. Src family kinase inhibitor PP2 efficiently inhibits cervical cancer cell proliferation through downregulating phospho-Src-Y416 and phospho-EGFR-Y1173.Mol Cell Biochem. 2011; 348:11-19.
Missbach M, Jeschke M, Feyen J, Muller K, Glatt M, Green J, Susa M. A novel inhibitor of the tyrosine kinase Src suppresses phosphorylation of its major cellular substrates and reduces bone resorption in vitro and in rodent models in vivo. Bone 1999; 24:437 – 449
Recchia I, Rucci N, Funari A, Migliaccio S, Taranta A, Longo M, Kneissel M, Susa M, Fabbro D, Teti A. Reduction of c-Src activity by substituted 5,7-diphenyl-pyrrolo[2,3-d]-pyrimidines induces osteoclast apoptosis in vivo and in vitro. Involvement of ERK1/2 pathway. Bone 2004; 34:65 – 79.
Recchia I, Rucci N, Festuccia C, Bologna M, MacKay AR, Migliaccio S, Longo M, Susa M, Fabbro D, Teti A. Pyrrolopyrimidine c-Src inhibitors reduce growth, adhesion, motility and invasion of prostate cancer cells in vitro. Eur J Cancer 2003; 39:1927 – 1935.
Hu Y, Liu Y, Pelletier S, Buchdunger E, Warmuth M, Fabbro D, Hallek M, Van Etten RA, Li S. Requirement of Src kinases Lyn, Hck and Fgr for BCR-ABL1-induced B-lymphoblastic leukemia but not chronic myeloid leukemia. Nat Genet 2004; 36:453 – 461.
Blake RA, Broome MA, Liu X, Wu J, Gishizky M, Sun L, Courtneidge SA. SU6656, a selective src family kinase inhibitor, used to probe growth factor signaling. J Mol Cell Biol 2000; 20:9018 – 9027.
Servitja JM, Marinissen MJ, Sodhi A, Bustelo XR, Gutkind JS. Rac1 function is required for Src-induced transformation. Evidence of a role for Tiam1 and Vav2 in Rac activation by Src. J Biol Chem 2003; 278:34339 – 34346.
Cuneo KC, Geng L, Tan J, Brousal J, Shinohara ET, Osusky K, Fu A, Shyr Y, Wu H, Hallahan DE. SRC family kinase inhibitor SU6656 enhances antiangiogenic effect of irradiation. Int J Radiat Oncol Biol Phys 2006; 64:1197 – 1203.
Morinaga K, Yamauchi T, Kimura S, Maekawa T, Ueda T. Overcoming imatinib resistance using Src inhibitor CGP76030, Abl inhibitor nilotinib and Abl/Lyn inhibitor INNO-406 in newly established K562 variants with BCR-ABL gene amplification. Int J Cancer. 2008; 11:2621-2627.
Brunton VG, Avizienyte E, Fincham VJ, Serrels B, Metcalf CA, Sawyer TK, Frame MC. Identification of Src-specific phosphorylation site on focal adhesion kinase: dissection of the role of Src SH2 and catalytic functions and their consequences for tumor cell behavior. Cancer Res 2005; 65:1335 – 1342.
Boyce BF, Xing L, Shakespeare W, Wang Y, Dalgarno D, Iuliucci J, Sawyer T. Regulation of bone remodeling and emerging breakthrough drugs for osteoporosis and osteolytic bone metastases. Kidney Intern. 2003; 85:52 – 55.
Wang Y, Metcalf CA III, Shakespeare WC, Sundaramoorthi R, Keenan TP, Bohacek RS, van Schravendijk MR, Violette SM, Narula SS, Dalgarno DC, Haraldson C, Keats J, Liou S, Mani U, Pradeepan S, RamM, Adams S, WeigeleM, Sawyer TK. Bone-targeted 2,6,9trisubstituted purines: novel inhibitors of Src tyrosine kinase for the treatment of bone diseases. Bioorg Med Chem Lett 2003; 13:3067 – 3070.
Boyce BF, Xing L, Yao Z, Yamashita T, Shakespeare WC, Wang Y, Metcalf CA III, Sundaramoorthi R, Dalgarno DC, Iuliucci JD, Sawyer TK. SRC inhibitors in metastatic bone disease. Clin Cancer Res 2006;12:6291s – 6295s.
El-Hashim AZ, Khajah MA, Renno WM, Babyson RS, Uddin M, Benter IF, Ezeamuzie C, Akhtar S. Src-dependent EGFR transactivation regulates lung inflammation via downstream signaling involving ERK1/2, PI3K δ /Akt and NF κ B induction in a murine asthma model. Sci Rep 2017; 7: 9919.
Han LY, Landen CN, Trevino JG, Halder J, Lin YG, Kamat AA, Kim TJ, MerrittWM, Coleman RL, Gershenson DM, Shakespeare WC, Wang Y, Sundaramoorth R, Metcalf CA , Dalgarno DC, Sawyer TK, Gallick GE, Sood AK. Antiangiogenic and antitumor effects of SRC inhibition in ovarian carcinoma. Cancer Res 2006; 66:8633 – 8639.
Trevino JG, Gray MJ, Nawrocki ST, Summy JM, Lesslie DP, Evans DB, Sawyer TK, ShakespeareWC, Watowich SS, Chiao PJ, McConkey DJ, Gallick GE. Src activation of Stat3 is an independent requirement from NF-kappaB activation for constitutive IL-8 expression in human pancreatic adenocarcinoma cells. Angiogenesis 2006; 9:101 – 110.
Boyce BF, Xing L, Yao Z, Shakespeare WC, Wang Y, Metcalf CA III, Sundaramoorthi R, Dalgarno DC, Iuliucci JD, Sawyer TK . Future anticatabolic therapeutic targets in bone disease. Ann NY Acad Sci 2006; 1068:447 – 457.
Lesslie DP, Summy JM, Parikh NU, Fan F, Trevino JG, Sawyer TK, Metcalf CA, Shakespeare WC, Hicklin DJ, Ellis LM, Gallick GE. Vascular endothelial growth factor receptor-1 mediates migration of human colorectal carcinoma cells by activation of Src family kinases. Br J Cancer 2006; 94:1710 – 1717.
Carragher NO, Walker SM, Scott Carragher LA, Harris F, Sawyer TK, Brunton VG, Ozanne BW, Frame MC. Calpain 2 and Src dependence distinguishes mesenchymal and amoeboid modes of tumour cell invasion: a link to integrin function. Oncogene 2006; 25:5726 – 5740.
Summy JM, Trevino JG, Lesslie DP, Baker CH, Shakespeare WC, Wang Y, Sundaramoorthi R, Metcalf CA III, Keats JA, Sawyer TK, Gallick GE. AP23846, a novel and highly potent Src family kinase inhibitor, reduces vascular endothelial growth factor and interleukin-8 expression in human solid tumor cell lines and abrogates downstream angiogenic processes. Mol Cancer Ther 2005; 4:1900 – 1911.
Brunton VG, Avizienyte E, Fincham VJ, Serrels B, Metcalf CA, Sawyer TK, Frame MC. Identification of Src-specific phosphorylation site on focal adhesion kinase: dissection of the role of Src SH2 and catalytic functions and their consequences for tumor cell behavior. Cancer Res 2005; 65:1335 – 1342.
O ’ Hare T, Pollock R, Stoffregen EP, Keats JA, Abdullah OM, Moseson EM, Rivera VM, Tang H, Metcalf CA III, Bohacek RS, Wang Y, Sundaramoorthi R, Shakespeare WC, Dalgarno D, Clackson T, Sawyer TK, Deininger MW, Druker BJ. Inhibition of wild-type and mutant BcrAbl by AP23464, a potent ATP-based oncogenic protein kinase inhibitor: implications for CML. Blood 2004;104: 2532 – 2539
Azam M, Nardi V, Shakespeare WC, Metcalf CA III, Bohacek RS, Wang Y, Sundaramoorthi R, Sliz P, Veach DR, BornmannWG, Clarkson B, DalgarnoDC, Sawyer TK, Daley GQ. Activity of dual SRC-ABL inhibitors highlights the role of BCR/ABL kinase dynamics in drug resistance. Proc Natl Acad Sci USA 2006; 103:9244 – 9249.
Corbin AS, Demehri S, Griswold IJ, Wang Y, Metcalf CA, Sundaramoorthi R, Shakespeare WC, Snodgrass J, Wardwell S, Dalgarno D, Iuliucci J, Sawyer TK, Heinrich MC, Druker BJ, Deininger MW. In vitro and in vivo activity of ATP-based kinase inhibitors AP23464 and AP23848 against activation-loop mutants of Kit.Blood 2005; 106:227 – 234.
Vultur A, Buettner R, Kowolik C, Liang W, Smith D, Boschelli F, Jove R. SKI-606 (bosutinib), a novel Src kinase inhibitor, suppresses migration and invasion of human breast cancer cells. Mol Cancer Ther 2008; 5:1185-1194.
Summy JM, Trevino JG, Lesslie DP, Baker CH, Shakespeare WC, Wang Y, Sundaramoorthi R, Metcalf CA 3rd, Keats JA, Sawyer TK, Gallick GE. AP23846, a novel and highly potent Src family kinase inhibitor, reduces vascular endothelial growth factor and interleukin-8 expression in human solid tumor cell lines and abrogates downstream angiogenic processes.Mol Cancer Ther 2005; 12:1900-1911.
Boschelli DH, Ye F, Wang YD, Dutia M, Johnson SL, Wu B, Miller K, Powell DW, YaczkoD, YoungM, TischlerM, ArndtK, DiscafaniC, Etienne C, Gibbons J, Grod J, Lucas J, Weber JM, Boschelli F. Optimization of 4-phenylamino-3-quinolinecarbonitriles as potent inhibitors of Src kinase activity. J Med Chem 2001; 44:3965 – 3977.
Golas JM, Lucas J, Etienne C, Golas J, DiscafaniC, Sridharan L, Boghaert E, Arndt K, Ye F, Boschelli DH, Li F, Titsch C, Huselton C, Chaudhary I, Boschelli F. SKI-606, a Src/Abl inhibitor with in vivo activity in colon tumor xenograft models. Cancer Res 2005; 65:5358 – 5364.
Boschelli DH, Wang YD, Johnson S, Wu B, Ye F, Barrios Sosa AC, Golas JM, Boschelli F. 7-Alkoxy-4-phenylamino-3-quinolinecarbonitriles as dual inhibitors of Src and Abl kinases. J Med Chem 2004; 47:599 – 601.
Boschelli DH, Wang YD, Ye F, Wu B, Zhang N, Dutia M, Powell DW, Wissner A, Arndt K, Weber JM, Boschelli F. Synthesis and Src kinase inhibitory activity of a series of 4-phenylamino-3-quinolinecarbonitriles. J Med Chem 2001; 44:822 – 833.
Wang YD, Miller K, Boschelli DH, Ye F, Wu B, Floyd MB, Powell DW, Wissner A, Weber JM, Boschelli F. Inhibitors of src tyrosine kinase: the preparation and structure-activity relationship of 4-anilino-3cyanoquinolines and 4-anilinoquinazolines. Bioorg Med Chem Lett 2000; 10:2477 – 2480.
Green TP, Fennell M, Whittaker R, Curwen J, Jacobs V, Allen J, Logie A, Hargreaves J, Hickinson DM, Wilkinson RW, Elvin P, Boyer B, Carragher N, Plé PA, Bermingham A, Holdgate GA, Ward WH, Hennequin LF, Davies BR, Costello GF. Preclinical anticancer activity of the potent, oral Src inhibitor AZD0530. Mol Oncol. 2009; 3:248-261.
Zimmerman J, Buchdunger E, Mett H, Meyer T, Lydon NB. Potent and selective inhibitors of the ABL-kinase: phenylaminopyrimidine (PAP) derivatives. Bioorg Med Chem Lett 1997; 7:187 – 192.
Mrad M, Imbert C, Garcia V, Rambow F, Therville N , Carpentier S, Ségui B, Levade T , Azar R, Marine JC, Diab-Assaf M, Colacios C, Andrieu-Abadie N. Downregulation of sphingosine kinase-1 induces protective tumor immunity by promoting M1 macrophage response in melanoma. Oncotarget 2016; 7:1873-71886.
Nakano H, Kobayashi E, Takahashi I, Tamaoki T, Kuzuu Y, Iba H. Staurosporine inhibits tyrosine-specific protein kinase activity of Rous sarcoma virus transforming protein p60. J Antibiot (Tokyo) 1987; 40:706 – 708.
Yoneda T, Lowe C, Lee C-H, Gutierrez G, Niewolna M, Williams PJ, Izbicka E, Uehara Y, Mundy GR, Herbimycin A. a pp60c-src tyrosine kinase inhibitor, inhibits osteoclastic bone resorption in vitro and hypercalcemia in vivo. J Clin Invest 1993; 91:2791 – 2795.
Slate DL, Lee RH, Rodriguez J, Crews P. The marine natural product, halistanol trisulfate, inhibits pp60v-src protein tyrosine kinase activity. Biochem Biophys Res Comm 1994; 203:260 – 264.
Maly DJ, Choong IC, Ellman JA. Combinatorial target-guided ligand assembly: identification of potent subtype-selective c-Src inhibitors. Proc Natl Acad Sci USA 2000; 97:2419 – 2424.
Kumar A1, Ye G, Wang Y, Lin X, Sun G, Parang K. Synthesis and structure-activity relationships of linear and conformationally constrained peptide analogues of CIYKYY as Src tyrosine kinase inhibitors. J Med Chem 2006; 49:3395-401.
Xu W, Doshi A, Lei M, Eck MJ, Harrison SC. Crystal structures of c-Src reveal features of its autoinhibitory mechanism. Mol Cell 1999; 5:629-38.
Anbalagan M, Carrier L, Glodowski S, Hangauer D, Shan B, Rowan BG. KX-01, a novel Src kinase inhibitor directed toward the peptide substrate site, synergizes with tamoxifen in estrogen receptor α positive breast cancer. Breast Cancer Res Treat 2012; 2:391-409.
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Copyright (c) 2018 Ahmed A. El-Rashedy, Asmaa A. Magd El-Din

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.


Journal of Innovations in Pharmaceutical and Biological Sciences is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Based on a work at