LEADER 00934nam0 22002531i 450 001 UON00117791 005 20231205102704.343 100 $a20020107d1961 |0itac50 ba 101 $aper 102 $aIR 105 $a|||| 1|||| 200 1 $aSa'eri dir-asna$f'Ali Dasti 210 $aTehran$cAmir Kabir$d1340h [1961] 215 $a235 p.$d22 cm 620 $aIR$dTihra?n$3UONL005570 686 $aIRA VI ABX$cIRAN - LETTERATURA - PERSIANO - CRITICA LETTERARIA - PERIODO ARCAICO E CLASSIC$2A 700 1$aDASTI$b'Ali$3UONV016768$0640037 712 $aAmir Kabir$3UONV246361$4650 801 $aIT$bSOL$c20240220$gRICA 899 $aSIBA - SISTEMA BIBLIOTECARIO DI ATENEO$2UONSI 912 $aUON00117791 950 $aSIBA - SISTEMA BIBLIOTECARIO DI ATENEO$dSI IRA VI ABX 031 $eSI MR 80069 7 031 996 $aSa'eri dir-asna$91309312 997 $aUNIOR LEADER 09782nam 2200649 a 450 001 9910141339303321 005 20200520144314.0 010 $a9786613619150 010 $a9781280589324 010 $a1280589329 010 $a9781118098134 010 $a1118098137 010 $a9781118098141 010 $a1118098145 010 $a9781118098127 010 $a1118098129 035 $a(CKB)2670000000159940 035 $a(EBL)697541 035 $a(OCoLC)779410061 035 $a(SSID)ssj0000622306 035 $a(PQKBManifestationID)11440832 035 $a(PQKBTitleCode)TC0000622306 035 $a(PQKBWorkID)10638496 035 $a(PQKB)10660345 035 $a(MiAaPQ)EBC697541 035 $a(PPN)17893285X 035 $a(Perlego)1013003 035 $a(EXLCZ)992670000000159940 100 $a20111220d2012 uy 0 101 0 $aeng 135 $aur|n|---||||| 181 $ctxt 182 $cc 183 $acr 200 00$aPolypharmacology in drug discovery /$fedited by Jens-Uwe Peters 205 $a1st ed. 210 $aHoboken, N.J. $cWiley$dc2012 215 $a1 online resource (544 p.) 300 $aDescription based upon print version of record. 311 08$a9780470590904 311 08$a0470590904 320 $aIncludes bibliographical references and index. 327 $aMachine generated contents note: List of contributors. Preface.Introduction: the case for polypharmacology Andrew L. Hopkins Part A: Polypharmacology - a safety concern in drug discovery. 1 The relevance of off-target polypharmacology Bruce D. Car 2 Screening for safety-relevant off-target activities Laszlo Urban, Steven Whitebread, Jacques Hamon, Dmitri Mikhailov and Kamal Azzaoui 2.1 Introduction. 2.2 General aspects. 2.3 Selection of off-targets. 2.4 In silico approaches to off-target profiling .2.5 Summary and conclusions. 3 Pharmacological promiscuity and molecular propertiesJens-Uwe Peters 3.1 Introduction: pharmacological promiscuity in the history of drug discovery. 3.2 Lipophilicity. 3.3 Molecular weight. 3.4 Ionisation state. 3.5 Other molecular descriptors and structural motifs. 3.6 Implications for drug discovery. 4 Kinases as antitargets in genotoxicity Stephan Kirchner 4.1 Protein Kinases and inhibitor-binding sites. 4.2 Cyclin-Dependent Kinases (CDKs) controlling unregulated cell proliferation. 4.3 Mitotic kinases as guardians protecting cells from aberrant chromosome segregation. 5 Activity at cardiovascular ion channels: a key issue for drug discoveryIan M. Bell, Mark T. Bilodeau and Armando A. Lagrutta 5.1 Introduction. 5.2 Screening methods. 5.3 Structural insights into the interaction between drugs and CV ion channels. 5.4 Medicinal Chemistry approaches. 5.5 Conclusion. 6 Prediction of side effects based on fingerprint profiling and data mining Jacques Migeon 6.1 Introduction to BioPrint. 6.2 The pharmacological fingerprint. 6.3 Antidepressant example. 6.4 Profile similarity at non-therapeutic targets. 6.5 Interpreting the polypharmacology profile. 6.6 Methods. 6.7 Patterns of activity. 6.8 Integrating function profile data with traditional pharmacological binding data. 6.9 Analysis of the antifungal tioconazole. 6.10 Conclusions. Part B: Polypharmacology - an opportunity for drug discovery. 7 Polypharmacological drugs - "magic shotguns" for psychiatric diseases Wesley K. Kroeze and Bryan L. Roth 7.1 Introduction. 7.2 Definition. 7.3 The discovery and extent of promiscuity among psychiatric drugs. 7.4 Why are so many psychiatric drugs promiscuous? 7.5 Conclusions. 8 Polypharmacological kinase inhibitors: new hopes for the therapy of cancer Annalisa Petrelli 8.1 Targeted therapies: a new era in the treatment of cancer. 8.2 The single-targeted therapy. 8.3 From single to multi-targeted drugs in cancer therapy. 8.4 Polypharmacology kinase inhibitors in clinical practice and under development. 8.5 Concluding remarks. 9 Polypharmacology as an emerging trend in antibacterial discovery Lynn L. Silver 9.1 Introduction. 9.2 Classical antibacterial polypharmacology. 9.3 New approaches to multi-targeted single pharmacophores. 9.4 Synthetic lethals. 9.5 Hybrid molecules. 9.6 Conclusions. 10 A "magic shotgun" perspective on anticonvulsant mechanisms Matt T. Bianchi and Kathy Chuang 10.1 Introduction. 10.2 Anticonvulsant mechanism. 10.3 Defining promiscuity. 10.4 Promiscuity: lessons from endogenous signaling. 10.5 Promiscuity: lessons from anticonvulsant electrophysiology. 10.6 Use of anticonvulsants in disorders other than epilepsy. 10.7 Experimental and theoretical support for a "Magic Shotgun" approach. 10.8 Current multi-target strategies. 10.9 Practical considerations. 10.10 Conclusion. 11 Selective Optimization of Side Activities (SOSA): a promising way for drug discovery Thierry Langer and Camille-Georges Wermuth 11.1 Introduction. 11.2 Definition and principle. 11.3 Rationale of SOSA. 11.4 Establishing the SOSA approach. 11.5 A successful example of the SOSA approach. 11.6 Other examples of SOSA switches. 11.7 Discussion. 11.8 Computer-assisted design using pharmacophores. 11.9 Conclusions. Part C: Selected approaches to polypharmacological drug discovery 12 Selective multi-targeted drugs Richard Morphy 12.1 Introduction. 12.2 Lead Generation. 12.3 Lead optimization. 12.4 Case studies. 12.5 Summary. 13 Computational multitarget drug discovery Jeremy A. Horst, Adrian Laurenzi, Brady Bernard and Ram Samudrala 13.1 Introduction. 13.2 The pharmacologic hunt of yester year. 13.3. Established technological advancements. 13.4. Computational drug discovery. 13.5. Recent technical improvements. 13.6. Emerging concepts. 13.7 Summary. 14 Behavior-based screening as an approach to polypharmacological ligands Dani Brunner, Vadim Alexandrov, Barbara Caldarone, Taleen Hanania, David Lowe, Jeff Schneider and Jayaraman Chandrasekhar 14.1 The Challenges of CNS Drug Discovery. 14.2 In vivo high throughput screening. 14.3 Screening libraries of compounds. 14.4 Relationship between molecular properties and in vivo CNS activity. 14.5 Following screening hits in secondary assays. 14.6 Potential therapeutic value of dual adenosine compounds. 14.7 Summary. 15 Multicomponent Therapeutics Alexis A. Borisy, Grant R. Zimmermann and Joseph Lehar 15.1 Introduction. 15.2 Drug synergies are statistically more context dependent. 15.3 How a synergistic mechanism can lead to therapeutic selectivity. 15.4 Discussion. Part D: Case studies 16 The discovery of sunitinib as a multitarget treatment of cancer Catherine Delbaldo, Camelia Colichi, Marie-Paule Sablin, Chantal Dreyer, Bertrand Billemont, Sandrine Faivre and Eric Raymond 16.1 A brief introduction to tumor angiogenesis. 16.2 The discovery of sunitinib: from drug design to first evidences of clinical activity. 16.3 Pharmacology of sunitinib. 16.4 Safety of sunitinib. 16.5 Activity of Sunitinib. 16.6 Surrogate imaging techniques to capture vascular changes. 16.7 Surrogate biomarkers. 16.8 Conclusion. 17 Antipsychotics Claus Riemer 17.1 Definition and diagnosis of schizophrenia. 17.2 Etiology and pathophysiology of schizophrenia. 17.3 Epidemiology. 17.4 Medical practice and treatment options. 17.5 Case studies. 17.6 CATIE. 17.7 Conclusions. 18 Triple Uptake Inhibitors ("Broad Spectrum" Antidepressants) Phil Skolnick 18.1 Introduction. 18.2 What is the rationale for developing triple uptake inhibitors as antidepressants? 18.3 Preclinical data. 18.4 Clinical data. 18.5 Concluding remarks. 19 Therapeutic potential of small molecules modulating the cyclooxygenase and 5-lipoxygenase pathway Stefan Laufer and Wolfgang Albrecht 19.1 Targets of the eicosanoid pathway. 19.2 Rationale for development of dual inhibitors of the cyclooxygenase and 5-lipoxygenase pathway. 19.3 Dual inhibitors of the cyclooxygenase and 5-lipoxygenase pathway. 19.4 Development of Licofelone. 19.5 Conclusions. 20 Drug research leading to imatinib and beyond to nilotinib Paul W. Manley and Jurg Zimmermann 20.1 Introduction. 20.2 Historical background. 20.3 BCR-ABL1 as the molecular target for CML therapy. 21 Towards antimalarial hybrid drugs Bernard Meunier 22 Multitarget drugs for the treatment of Alzheimer's disease Andrea Cavalli and Maria Laura Bolognesi 22.1 Introduction. 22.2 Case studies. 22.3 Conclusions and perspectives. 23 Carbonic anhydrases: off-targets, add-on activities, or emerging novel targets? Claudiu Supuran 23.1 Introduction. 23.2 Carbonic anhydrase inhibition. 23.3 Topiramate and zonisamide, antiepileptics with potent antiobesity action. 23.4 Sulfonamide coxibs with antitumor activity due to CA IX/XII inhibition. 23.5 Sulfamates with steroid sulfatase and carbonic anhydrase inhibitory action as anticancer agents in clinical development. 23.6 Lacosamide, an antiepileptic with a strange binding mode to Cas. 23.7 The protein tyrosine kinase inhibitors imatinib and nilotinib strongly inhibit several mammalian CA isoforms. 23.8 Conclusions. 330 $a"Covers the two-sided nature of polypharmacology--its contribution to adverse drug reactions and its benefit in certain therapeutic drug classes. Addresses the important topic of polypharmacology in drug discovery, a subject that has not been thoroughly covered outside of scattered journal articles Overviews state-of-the-art approaches and developments to help readers understand concepts and issues related to polypharmacology"--Provided by publisher. 606 $aDrugs$xDesign 606 $aPolypharmacy 615 0$aDrugs$xDesign. 615 0$aPolypharmacy. 676 $a615.19 701 $aPeters$b Jens-Uwe$0994169 801 0$bMiAaPQ 801 1$bMiAaPQ 801 2$bMiAaPQ 906 $aBOOK 912 $a9910141339303321 996 $aPolypharmacology in drug discovery$92276883 997 $aUNINA LEADER 02462nam 22005654a 450 001 9910966488603321 005 20251117074457.0 010 $a0-8132-1602-8 035 $a(CKB)2440000000014008 035 $a(SSID)ssj0000376306 035 $a(PQKBManifestationID)11298958 035 $a(PQKBTitleCode)TC0000376306 035 $a(PQKBWorkID)10328054 035 $a(PQKB)10847049 035 $a(OCoLC)646786294 035 $a(MdBmJHUP)muse24086 035 $a(Au-PeEL)EBL3134747 035 $a(CaPaEBR)ebr10267272 035 $a(OCoLC)922996433 035 $a(MiAaPQ)EBC3134747 035 $a(EXLCZ)992440000000014008 100 $a20051115d2006 uy 0 101 0 $aeng 135 $aurcn||||||||| 181 $ctxt 182 $cc 183 $acr 200 10$aForm and being $estudies in Thomistic metaphysics /$fLawrence Dewan 205 $a1st ed. 210 $aWashington, D.C. $cCatholic University of America Press$dc2006 215 $axv, 265 p 225 1 $aStudies in philosophy and the history of philosophy ;$vv. 45 300 $aBibliographic Level Mode of Issuance: Monograph 311 08$a0-8132-1461-0 320 $aIncludes bibliographical references (p. 249-254) and indexes. 327 $aWhat is metaphysics? -- What does it mean to study being "as being"? -- St. Thomas and the seed of metaphysics -- St. Thomas, physics, and the principle of metaphysics -- St. Thomas and the principle of causality -- St. Thomas and analogy : the logician and the metaphysician -- The importance of substance -- St. Thomas, metaphysics, and formal causality -- St. Thomas, metaphysical procedure, and the formal cause -- St. Thomas, form, and incorruptibility -- St. Thomas and the distinction between form and esse in caused things -- Nature as a metaphysical object -- The individual as a mode of being according to Thomas Aquinas. 330 $aContains thirteen essays by Lawrence Dewan on metaphysics, the vision of reality from the viewpoint of being. 410 0$aStudies in philosophy and the history of philosophy ;$vv. 45. 606 $aThomas, -- Aquinas, Saint, -- 1225?-1274 615 0$aThomas, -- Aquinas, Saint, -- 1225?-1274. 676 $a100 s 676 $a189/.4 700 $aDewan$b Lawrence$f1932-$01857575 801 0$bMiAaPQ 801 1$bMiAaPQ 801 2$bMiAaPQ 906 $aBOOK 912 $a9910966488603321 996 $aForm and being$94458480 997 $aUNINA