Anticandidal Therapeutics: Discovery and Development

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
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