LEADER 05258nam 2200637Ia 450 001 9910451715203321 005 20200520144314.0 010 $a1-281-76368-3 010 $a9786611763688 010 $a0-08-055495-4 035 $a(CKB)1000000000490102 035 $a(EBL)403943 035 $a(OCoLC)476216470 035 $a(SSID)ssj0000117289 035 $a(PQKBManifestationID)11132097 035 $a(PQKBTitleCode)TC0000117289 035 $a(PQKBWorkID)10061959 035 $a(PQKB)11558919 035 $a(MiAaPQ)EBC403943 035 $a(Au-PeEL)EBL403943 035 $a(CaPaEBR)ebr10378993 035 $a(CaONFJC)MIL176368 035 $a(EXLCZ)991000000000490102 100 $a20071015d2008 uy 0 101 0 $aeng 135 $aur|n|---||||| 181 $ctxt$2rdacontetn 182 $cc$2rdamedia 183 $acr$2rdacarrier 200 10$aCancer drug design and discovery$b[electronic resource] /$fStephen Neidle 210 $aLondon $cAcademic$dc2008 215 $a1 online resource (517 p.) 300 $aDescription based upon print version of record. 311 $a0-12-369448-5 320 $aIncludes bibliographical references and index. 327 $aFront Cover; Cancer Drug Design and Discovery; Copyright Page; Contents; About the editor; Contributors; Introduction; PART I: BASIC PRINCIPLES; Chapter 1 Modern cancer drug discovery: integrating targets, technologies and treatments; 1.1 Introduction: changing times; 1.2 Successes and limitations; 1.3 Integrated small-molecule drug discovery and development; 1.4 New molecular targets: the ""druggable"" cancer genome; 1.5 From drug target to development candidate; 1.6 Examples of case histories for molecularly targeted cancer therapeutics 327 $a1.7 Biomarkers, the pharmacological audit trail and clinical development1.8 Conclusions and outlook: towards individualized molecular cancer medicine; References; Chapter 2 Preclinical pharmacology and in vivo models; 2.1 Introduction; 2.2 Contemporary preclinical cancer drug discovery; 2.3 In vitro pharmacological evaluation; 2.4 Information gained from in vitro cell lines; 2.5 In vivo pharmacokinetics (PK) and pharmacodynamics (PD): continuing the pharmacological audit trail; 2.6 In vivo anti-tumor models: choice and predictiveness?; 2.7 Concluding remarks; References 327 $aChapter 3 Clinical trial designs for more rapid proof-of-principle and approval3.1 Introduction; 3.2 NDA plan at the time of IND; 3.3 Phase I trial design innovations; 3.4 Concept of a continuous Phase I; 3.5 Phase II trial design innovations; 3.6 Phase III trial design innovations (enrichment designs); 3.7 Other approaches to enrich trial populations; 3.8 Innovations in design and selection of endpoints; 3.9 Regulatory strategies; 3.10 Other approaches to accelerate drug development; 3.11 New perspectives; 3.12 Summary; References; PART II: METHODOLOGY 327 $aChapter 4 Structural biology and anticancer drug design4.1 Introduction; 4.2 High-throughput X-ray crystallography; 4.3 Structural biology and structure-based drug design; 4.4 Fragment screening using X-ray crystallography; 4.5 Case history: cyclin-dependent kinase inhibitors, from fragment hit to clinical candidate; 4.6 Compound profiling; 4.7 Conclusions; References; Chapter 5 Natural product chemistry and anticancer drug discovery; 5.1 Introduction; 5.2 Exemestane (aromasin); 5.3 Fulvestrant/faslodex; 5.4 Flavonoids; 5.5 Bexarotene (targretin); 5.6 Epothilones; 5.7 Maytansine 327 $a5.8 Geldanamycin5.9 UCN-01; 5.10 Camptothecin; 5.11 Prodigiosin; 5.12 Azacitidine; 5.13 FK-288; 5.14 Hemiasterlin; 5.15 Calicheamicin; 5.16 Conclusion; References; Chapter 6 Pharmacokinetics and ADME optimization in drug discovery; 6.1 Introduction; 6.2 Absorption; 6.3 Distribution; 6.4 Metabolism; 6.5 Elimination; 6.6 Biochemical barriers to drug therapy: efflux transporters; 6.7 Induction; 6.8 Conclusions; References; PART III: DRUGS IN THE CLINIC; Chapter 7 Temozolomide: from cytotoxic to molecularly-targeted agent; 7.1 Introduction 327 $a7.2 Towards imidazotetrazines and azolastone (mitozolomide) 330 $aThe ultimate source of information on the design of new anticancer agents, emphasizing small molecules, this newest work covers recent notable successes resulting from the human genome and cancer genomics projects. These advances have provided information on targets involved in specific cancers that are leading to effective medicines for at least some of the common solid tumors. Unique sections explain the basic underlying principles of cancer drug development and provide a practical introduction to modern methods of drug design. Appealing to a broad audience, this is an excellent reference fo 606 $aAntineoplastic agents$xDevelopment 606 $aAntineoplastic agents$xDesign 608 $aElectronic books. 615 0$aAntineoplastic agents$xDevelopment. 615 0$aAntineoplastic agents$xDesign. 676 $a616.994061 700 $aNeidle$b Stephen$099434 801 0$bMiAaPQ 801 1$bMiAaPQ 801 2$bMiAaPQ 906 $aBOOK 912 $a9910451715203321 996 $aCancer drug design and discovery$91926172 997 $aUNINA