دانلود کتاب Anticandidal Therapeutics: Discovery and Development

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Anticandidal TherapeuticsDiscovery and DevelopmentAwanish KumarAssociate Professor, Department of Biotechnology, National I ... Copyright Dedication Preface Acknowledgments 1. History of infection Introduction Introduction to plague Types of plague 14th century plagues Plague of Athens Second plague pandemic Black Death Third plague pandemic Smallpox Tuberculosis Spanish flu HIV/AIDS Swine flu COVID-19 (current pandemic) A note on the future References 2. Brief introduction on infection Introduction References 3. Fungal diseases and antifungal drugs Introduction Superficial mycoses Cutaneous mycoses Subcutaneous mycoses Systemic or invasive mycoses Candidal infection Biofilm formation Adhesion and invasins Contact sensing and thigmotropism Hydrolytic enzymes pH sensing and regulation Metabolic adaptation Environmental stress response Heat shock protein Metal acquisition Antifungal agents Azoles Polyenes Echinocandins Allylamines Other drugs Mechanism of antifungal resistance Resistance to azoles Alteration of drug target Upregulation of multidrug transporters Cellular stress responses Biofilms Modification of ergosterol biosynthetic pathway Chromosomal alterations Resistance to polyenes Resistance to echinocandins Upregulation of multidrug transporters Drug efflux References 4. Multidrug transporters of fungal pathogen Candida Introduction ABC transporters MFS transporters Regulation of MDR PDR1 and PDR3 are xenobiotic receptor in S. cerevisiae Xenobiotic regulation Efflux pumps regulation References 5. Essential anticandidal targets Fungal cell wall Fungal membrane components Inhibition of heat shock protein 90 Inhibition of calcineurin signaling Signaling pathways Cell cycle control pathways Membrane transporters Other surface targets Cross-talk References 6. Stages of anticandidal agent development Introduction Drug target discovery Screening HIT identification Lead optimization Experimentation Characterization of product Formulation, delivery, packaging development Pharmacokinetics and drug disposition Preclinical testing and IND application Acute studies Repeated dose studies Generic toxicity studies Reproductive toxicity studies Carcinogenicity studies Toxicokinetic studies Bioanalytical testing Clinical trials Postmarketing surveillance References 7. Recent trends and progress in antifungal translational research Introduction Translational research and strategy in fungal infection References 8. Clinical status of anticandidal therapeutic agents Introduction Synthetic compounds as futuristic antifungal Olorofim: orotomides (F901318) Natural compounds as promising antifungal Curcumin Thymol Berberine Tetrandrine Antifungals in different stage of clinical trials Rezafungin Ibrexafungerp (SCY-078) Fosmanogepix (APX001) Nikkomycin Z Tetrazoles Encochleated amphotericin B (MAT2203) Aureobasidin A F901318 (olorofim) VL-2397 T-2307 AR-12 References 9. Drug repurposing for development of effective anticandidals Introduction References 10. Commercial aspects of drug development Introduction Drug development process The design of a clinical trial Different types of clinical research Informed consent The investigational new drug process Drug review New drug application Postmarketing drug safety monitoring Generic drugs Reasons for catastrophic marketing failures Failures of pharmaceutical companies References 11. Challenges and future prospects Introduction Gray areas in drug discovery research Cost of new drug development Out-of-pocket costs Success rates Development timelines Cost of capital Preclinical phase Clinical trials phase Macroeconomic, demographic, and policy factors affecting R&D funding References Index A B C D E F G H I L M N O P Q R S T U V W X