{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T08:38:57Z","timestamp":1770971937363,"version":"3.50.1"},"reference-count":57,"publisher":"Elsevier BV","issue":"2-3","license":[{"start":{"date-parts":[[1999,5,1]],"date-time":"1999-05-01T00:00:00Z","timestamp":925516800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmacology &amp; Therapeutics"],"published-print":{"date-parts":[[1999,5]]},"DOI":"10.1016\/s0163-7258(98)00066-7","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T02:34:30Z","timestamp":1027650870000},"page":"231-239","source":"Crossref","is-referenced-by-count":156,"title":["Protein Tyrosine Kinase Inhibitors as Novel Therapeutic Agents"],"prefix":"10.1016","volume":"82","author":[{"given":"Alexander","family":"Levitzki","sequence":"first","affiliation":[]}],"member":"78","reference":[{"key":"10.1016\/S0163-7258(98)00066-7_BIB1","doi-asserted-by":"crossref","first-page":"4518","DOI":"10.1016\/S0021-9258(18)42864-5","article-title":"Selective interactions of transforming and normal Abl proteins with ATP, tyrosine copolymer substrates and tyrphostins","volume":"267","author":"Anafi","year":"1992","journal-title":"J. Biol. Chem."},{"key":"10.1016\/S0163-7258(98)00066-7_BIB2","first-page":"S13","article-title":"Expression of the erbB-2 family of growth factor receptors and their ligands in breast cancers. Implication for tumor biology and clinical behavior","volume":"102","author":"Bacus","year":"1994","journal-title":"Am. J. Clin. Pathol."},{"key":"10.1016\/S0163-7258(98)00066-7_BIB3","doi-asserted-by":"crossref","first-page":"1960","DOI":"10.1161\/01.CIR.97.19.1960","article-title":"PDGF-receptor tyrosine kinase blocker AG 1295 selectively attenuates smooth muscle cell growth in vitro and reduces neointimal formation after balloon angioplasty in swine","volume":"19","author":"Banai","year":"1998","journal-title":"Circulation"},{"key":"10.1016\/S0163-7258(98)00066-7_BIB4","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1111\/j.1600-0625.1995.tb00227.x","article-title":"Tyrphostins suppress the growth of psoriatic keratinocytes","volume":"4","author":"Ben-Bassat","year":"1995","journal-title":"Exp. Dermatol."},{"key":"10.1016\/S0163-7258(98)00066-7_BIB5","first-page":"3741","article-title":"Blockers of the EGF receptor and of Cdk2 activation induce growth arrest, differentiation, and apoptosis of HPV 16 immortalized human keratinocytes","volume":"57","author":"Ben-Bassat","year":"1997","journal-title":"Cancer Res."},{"key":"10.1016\/S0163-7258(98)00066-7_BIB6","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1006\/exnr.1998.6971","article-title":"Suppression of experimental autoimmune encephalomyelitis by tyrphostin AG-556","volume":"154","author":"Brenner","year":"1998","journal-title":"Exp. Neurol."},{"key":"10.1016\/S0163-7258(98)00066-7_BIB7","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1021\/jm9503613","article-title":"Tyrosine kinase inhibitors. 8. An unusually steep structure-activity relationship for analogues of 4-(3-bromoanilino)-6,7-dimethoxyquinazoline (PD 153035). A potent inhibitor of the epidermal growth factor receptor","volume":"39","author":"Bridges","year":"1996","journal-title":"J. Med. Chem."},{"key":"10.1016\/S0163-7258(98)00066-7_BIB8","first-page":"813","article-title":"4,5-Bis(4-fluoroanilino)phthalimide","volume":"1","author":"Buchdunger","year":"1995","journal-title":"Clin. Cancer Res."},{"key":"10.1016\/S0163-7258(98)00066-7_BIB9","doi-asserted-by":"crossref","first-page":"2558","DOI":"10.1073\/pnas.92.7.2558","article-title":"Selective inhibition of the platelet-derived growth factor signal transduction pathway by a protein-tyrosine kinase inhibitor of the 2-phenylaminopyrimidine class","volume":"92","author":"Buchdunger","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/S0163-7258(98)00066-7_BIB10","article-title":"Effects of the tyrosine kinase inhibitor AG957 and an antifas receptor antibody on CD34+ chronic myelogenous leukemia progenitor cells","volume":"in press","author":"Carlos-Stella","year":"1999","journal-title":"Blood"},{"key":"10.1016\/S0163-7258(98)00066-7_BIB11","doi-asserted-by":"crossref","first-page":"14845","DOI":"10.1073\/pnas.93.25.14845","article-title":"The TEL\/platelet-derived growth factor beta receptor (PDGF beta R) fusion in chronic myelomonocytic leukemia is a transforming protein that self-associates and activates PDGF beta R kinase-dependent signaling pathways","volume":"10","author":"Carroll","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/S0163-7258(98)00066-7_BIB12","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/S1074-7613(00)80011-4","article-title":"Constitutive activation of Stat3 signaling confers resistance to apoptosis in human U266 myeloma cells","volume":"10","author":"Catlett-Falcone","year":"1999","journal-title":"Immunity"},{"key":"10.1016\/S0163-7258(98)00066-7_BIB13","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1038\/nm0596-561","article-title":"Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells","volume":"2","author":"Druker","year":"1996","journal-title":"Nature Med."},{"key":"10.1016\/S0163-7258(98)00066-7_BIB14","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1083\/jcb.113.4.857","article-title":"The inhibition of EGF-dependent proliferation of keratinocytes by tyrosine kinase blockers","volume":"113","author":"Dvir","year":"1991","journal-title":"J. Cell Biol."},{"key":"10.1016\/S0163-7258(98)00066-7_BIB15","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1126\/science.8066447","article-title":"A specific inhibitor of the epidermal growth factor receptor tyrosine kinase","volume":"265","author":"Fry","year":"1994","journal-title":"Science"},{"key":"10.1016\/S0163-7258(98)00066-7_BIB16","doi-asserted-by":"crossref","first-page":"2170","DOI":"10.1021\/jm950727b","article-title":"Tyrphostin. 5. Potent inhibitors of PDGF receptor tyrosine kinase. SAR in quinixalines, quinolines and indole tyrphostins","volume":"39","author":"Gazit","year":"1996","journal-title":"J. Med. Chem."},{"key":"10.1016\/S0163-7258(98)00066-7_BIB17","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.1016\/0968-0896(96)00107-1","article-title":"Tyrphostin. 4. Highly potent inhibitors of EGF receptor kinase. Structure activity relationship study of 4-anilido quinazolines","volume":"8","author":"Gazit","year":"1996","journal-title":"Bioorg. Med. Chem."},{"key":"10.1016\/S0163-7258(98)00066-7_BIB18","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/0021-9150(96)05868-6","article-title":"Controlled delivery of a tyrphostin inhibits intimal hyperplasia in rat carotid artery injury model","volume":"125","author":"Golomb","year":"1996","journal-title":"Atherosclerosis"},{"key":"10.1016\/S0163-7258(98)00066-7_BIB19","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/S0079-6468(08)70307-2","article-title":"Protein tyrosine kinase inhibitors","volume":"33","author":"Groundwater","year":"1996","journal-title":"Prog. Med. Chem."},{"key":"10.1016\/S0163-7258(98)00066-7_BIB20","first-page":"3859","article-title":"Tyrphostin AG 1478 preferentially inhibits human glioma cells expressing truncated rather than wild-type epidermal growth factor receptors","volume":"56","author":"Han","year":"1996","journal-title":"Cancer Res."},{"key":"10.1016\/S0163-7258(98)00066-7_BIB21","doi-asserted-by":"crossref","first-page":"5572","DOI":"10.1093\/emboj\/16.18.5572","article-title":"Crystal structure of the activated insulin receptor tyrosine kinase, in complex with peptide substrate and ATP analog","volume":"16","author":"Hubbard","year":"1997","journal-title":"EMBO J."},{"key":"10.1016\/S0163-7258(98)00066-7_BIB22","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1038\/372746a0","article-title":"Crystal structure of the tyrosine kinase domain of the human insulin receptor","volume":"372","author":"Hubbard","year":"1994","journal-title":"Nature"},{"key":"10.1016\/S0163-7258(98)00066-7_BIB23","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1038\/nm0695-541","article-title":"Inhibition of cellular ras prevents smooth muscle cell proliferation after vascular injury in vivo","volume":"1","author":"Indolfi","year":"1995","journal-title":"Nature Med."},{"key":"10.1016\/S0163-7258(98)00066-7_BIB24","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1097\/00001813-199404000-00013","article-title":"Tyrphostin induced growth inhibition","volume":"5","author":"Kaur","year":"1994","journal-title":"Anticancer Drugs"},{"key":"10.1016\/S0163-7258(98)00066-7_BIB25","doi-asserted-by":"crossref","first-page":"H513","DOI":"10.1152\/ajpheart.1998.274.2.H513","article-title":"Protein tyrosine phosphorylation mediated TNF-induced endothelial-neutrophil adhesion in vitro","volume":"43","author":"Kelly","year":"1998","journal-title":"Am. J. Physiol. (Heart Circ. Physiol.)"},{"key":"10.1016\/S0163-7258(98)00066-7_BIB26","first-page":"6106","article-title":"Selective platelet-derived growth factor receptor kinase blockers reverse sis-transformation","volume":"54","author":"Kovalenko","year":"1994","journal-title":"Cancer Res."},{"key":"10.1016\/S0163-7258(98)00066-7_BIB27","doi-asserted-by":"crossref","first-page":"6260","DOI":"10.1021\/bi962553l","article-title":"Phosphorylation site-specific inhibition of platelet-derived growth factor b-receptor autophosphorylation by the receptor blocking tyrphostin AG 1296","volume":"36","author":"Kovalenko","year":"1997","journal-title":"Biochemistry"},{"key":"10.1016\/S0163-7258(98)00066-7_BIB28","doi-asserted-by":"crossref","first-page":"3275","DOI":"10.1096\/fasebj.6.14.1426765","article-title":"Tyrphostins","volume":"6","author":"Levitzki","year":"1992","journal-title":"FASEB J."},{"key":"10.1016\/S0163-7258(98)00066-7_BIB29","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1432-1033.1994.tb20020.x","article-title":"Signal transduction therapy","volume":"226","author":"Levitzki","year":"1994","journal-title":"Eur. J. Biochem."},{"key":"10.1016\/S0163-7258(98)00066-7_BIB30","first-page":"175","article-title":"SRC as a target for anti-cancer drugs","volume":"11","author":"Levitzki","year":"1996","journal-title":"Anticancer Drug Des."},{"key":"10.1016\/S0163-7258(98)00066-7_BIB31","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/S0955-0674(96)80071-8","article-title":"Targeting signal transduction for disease therapy","volume":"8","author":"Levitzki","year":"1996","journal-title":"Curr. Opin. Cell. Biol."},{"key":"10.1016\/S0163-7258(98)00066-7_BIB32","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1007\/BF02990952","article-title":"Targeting signal transduction for disease therapy","volume":"14","author":"Levitzki","year":"1997","journal-title":"Med. Oncol."},{"key":"10.1016\/S0163-7258(98)00066-7_BIB33","first-page":"731","article-title":"Altered efficacy and selectivity of tyrosine kinase inhibitors of the activated states of protein tyrosine kinases","volume":"13","author":"Levitzki","year":"1998","journal-title":"Anticancer Drug Des."},{"key":"10.1016\/S0163-7258(98)00066-7_BIB34","doi-asserted-by":"crossref","first-page":"1782","DOI":"10.1126\/science.7892601","article-title":"Tyrosine kinase inhibition","volume":"267","author":"Levitzki","year":"1995","journal-title":"Science"},{"key":"10.1016\/S0163-7258(98)00066-7_BIB35","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1172\/JCI119578","article-title":"Tyrosine kinase inhibition ameliorates the hyperdynamic state and decreases nitric oxide production in cirrhotic rats with portal hypertension and ascites","volume":"100","author":"Lopez-Talavera","year":"1997","journal-title":"J. Clin. Invest."},{"key":"10.1016\/S0163-7258(98)00066-7_BIB36","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1038\/379645a0","article-title":"Inhibition of recurrent human pre-B acute lymphoblastic leukemia by Jak-2 tyrosine kinase inhibitor","volume":"379","author":"Meydan","year":"1996","journal-title":"Nature"},{"key":"10.1016\/S0163-7258(98)00066-7_BIB37","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1126\/science.276.5314.955","article-title":"Structure of the tyrosine kinase domain of fibroblast growth factor receptor in complex with inhibitors","volume":"276","author":"Mohammadi","year":"1997","journal-title":"Science"},{"key":"10.1016\/S0163-7258(98)00066-7_BIB38","doi-asserted-by":"crossref","first-page":"5724","DOI":"10.1073\/pnas.95.10.5724","article-title":"Drug resistance of human glioblastoma cells conferred by a tumor-specific mutant epidermal growth factor receptor through modulation of Bcl-XL and caspase-3-like proteases","volume":"95","author":"Nagane","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/S0163-7258(98)00066-7_BIB39","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1126\/science.8191285","article-title":"Prevention of LPS-induced lethal toxicity by tyrosine kinase blockers","volume":"264","author":"Novogrodsky","year":"1994","journal-title":"Science"},{"key":"10.1016\/S0163-7258(98)00066-7_BIB40","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1111\/j.1432-1033.1994.1047b.x","article-title":"Epidermal growth factor dependent activation of Src family kinases","volume":"225","author":"Osherov","year":"1994","journal-title":"Eur. J. Biochem."},{"key":"10.1016\/S0163-7258(98)00066-7_BIB41","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.1210\/en.138.4.1427","article-title":"Specific inhibition of insulin-like growth factor-1 and insulin receptor tyrosine kinase activity and biological functions by tyrphostins","volume":"138","author":"Parrizas","year":"1997","journal-title":"Endocrinology"},{"key":"10.1016\/S0163-7258(98)00066-7_BIB42","doi-asserted-by":"crossref","first-page":"20638","DOI":"10.1016\/S0021-9258(19)36734-1","article-title":"Kinetic model for the epidermal growth factor (EGF) receptor tyrosine kinase and a possible mechanism of its activation by EGF","volume":"267","author":"Posner","year":"1992","journal-title":"J. Biol. Chem."},{"key":"10.1016\/S0163-7258(98)00066-7_BIB43","first-page":"673","article-title":"Kinetics of inhibition of the tyrosine kinase activity of the epidermal growth factor receptor and analysis by a new computer program","volume":"45","author":"Posner","year":"1994","journal-title":"Mol. Pharmacol."},{"key":"10.1016\/S0163-7258(98)00066-7_BIB44","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1056\/NEJM198602203140806","article-title":"The pathogenesis of atherosclerosis\u2014an update","volume":"314","author":"Rewcastle","year":"1986","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/S0163-7258(98)00066-7_BIB45","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1056\/NEJM197608122950707","article-title":"The pathogenesis of atherosclerosis","volume":"295","author":"Ross","year":"1976","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/S0163-7258(98)00066-7_BIB46","article-title":"Crystal structure of Hck in complex with a Src family-selective tyrosine kinase inhibitor","volume":"in press","author":"Schindler","year":"1999","journal-title":"Mol. Cell."},{"key":"10.1016\/S0163-7258(98)00066-7_BIB47","doi-asserted-by":"crossref","first-page":"1966","DOI":"10.1172\/JCI119364","article-title":"Tyrphostin AG 556 improves survival and reduces multiorgan failure in canine E. coli peritonitis","volume":"99","author":"Sevransky","year":"1997","journal-title":"J. Clin. Invest."},{"key":"10.1016\/S0163-7258(98)00066-7_BIB48","doi-asserted-by":"crossref","first-page":"2077","DOI":"10.1182\/blood.V86.6.2077.bloodjournal8662077","article-title":"JAK 3 protein kinase mediates interleukin-7 induced activation of phosphatidyl insositol-3-kinase","volume":"86","author":"Sharfe","year":"1995","journal-title":"Blood"},{"key":"10.1016\/S0163-7258(98)00066-7_BIB49","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1038\/385602a0","article-title":"Crystal structure of the Src family tyrosine kinase Hck","volume":"385","author":"Sicheri","year":"1997","journal-title":"Nature"},{"key":"10.1016\/S0163-7258(98)00066-7_BIB50","first-page":"3540","article-title":"Flk-1 as a target for tumor growth inhibition","volume":"56","author":"Strawn","year":"1996","journal-title":"Cancer Res."},{"key":"10.1016\/S0163-7258(98)00066-7_BIB51","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1021\/jm950692f","article-title":"Tyrosine kinase inhibitors. 9. Synthesis and evaluation of fused tricyclic quinazoline analogues as ATP site inhibitors of the tyrosine kinase activity of the epidermal growth factor receptor","volume":"39","author":"Sun","year":"1996","journal-title":"J. Med. Chem."},{"key":"10.1016\/S0163-7258(98)00066-7_BIB52","doi-asserted-by":"crossref","first-page":"2285","DOI":"10.1021\/jm960118j","article-title":"4-(Phenylamino)pyrrolopyrimidines","volume":"39","author":"Traxler","year":"1996","journal-title":"J. Med. Chem."},{"key":"10.1016\/S0163-7258(98)00066-7_BIB53","first-page":"1068","article-title":"Enhancement of chemosensitivity by tyrphostin AG 825 in high-p185neu expressing non-small cell lung cancer cells","volume":"56","author":"Tsai","year":"1996","journal-title":"Cancer Res."},{"key":"10.1016\/S0163-7258(98)00066-7_BIB54","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1093\/infdis\/173.4.927","article-title":"Late administration of a lipophilic tyrosine kinase inhibitor prevents lipopolysacharide and Escherichia coli-induced lethal toxicity","volume":"173","author":"Vanichkin","year":"1996","journal-title":"J. Infect. Dis."},{"key":"10.1016\/S0163-7258(98)00066-7_BIB55","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1016\/0006-2952(94)90042-6","article-title":"Epidermal growth factor receptor tyrosine kinase investigation of catalytic mechanism, structure-based searching and discovery of a potent inhibitor","volume":"48","author":"Ward","year":"1994","journal-title":"Biochem. Pharmacol."},{"key":"10.1016\/S0163-7258(98)00066-7_BIB56","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1126\/science.3263702","article-title":"Blocking of EGF-dependent cell proliferation by EGF receptor kinase inhibitors","volume":"242","author":"Yaish","year":"1988","journal-title":"Science"},{"key":"10.1016\/S0163-7258(98)00066-7_BIB57","first-page":"4430","article-title":"The antiproliferative effects of tyrosine kinase inhibitors tyrphostins on a human squamous cell carcinoma in vitro and in nude mice","volume":"51","author":"Yoneda","year":"1991","journal-title":"Cancer Res."}],"container-title":["Pharmacology &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0163725898000667?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0163725898000667?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2021,5,14]],"date-time":"2021-05-14T11:17:07Z","timestamp":1620991027000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0163725898000667"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1999,5]]},"references-count":57,"journal-issue":{"issue":"2-3","published-print":{"date-parts":[[1999,5]]}},"alternative-id":["S0163725898000667"],"URL":"https:\/\/doi.org\/10.1016\/s0163-7258(98)00066-7","relation":{},"ISSN":["0163-7258"],"issn-type":[{"value":"0163-7258","type":"print"}],"subject":[],"published":{"date-parts":[[1999,5]]}}}