Protein Kinase Inhibitors

Protein Kinase Inhibitors: From Discovery to Therapeutics offers a foundational, pragmatic overview of protein kinases inhibitors and their potential role in disease modulation and treatment. Here, international experts in the field offer an integrated discussion of kinase inhibitor biology, biomarker discovery, and methods for drug design and development. After a brief overview of kinases and kinase inhibitors, subsequent chapters discuss individual kinases that are representative of the wider kinases and kinase families, including their roles in disease pathogenesis, underlying mechanisms, potential inhibitors and their modes of action for therapeutic modulation.

Several potential drugs under different stages of clinical trials are discussed, including their relevance to cancer, diabetes, obesity, cardiovascular, neurological, and auto-immune and inflammatory disease, among other disorders. The book also addresses the challenges and opportunities for future kinase inhibitor development.

Cover
Title page
Table of Contents
Copyright
Contributors
Preface
Chapter 1: Kinase inhibitors: An overview
Abstract
1: Introduction
2: Human kinome
3: Kinase directed signaling networks
4: Kinase as a drug target
5: Kinase inhibitors
6: Structural features of kinase inhibitors
7: History of kinase inhibitor
8: Current scenario in kinase inhibitor development
9: Success stories
10: Conclusion and future prospect
References
Chapter 2: Protein kinase inhibitors and cancer targeted therapy
Abstract
1: Introduction
2: Protein kinases features
3: Chemical kinase inhibitor
4: Natural bioactive as kinase inhibitors
5: Nanomaterial-based kinase targeting
6: Epilogue and perspective
References
Chapter 3: Drug discovery for cancer therapy with special reference to inhibitors of protein kinase pathway
Abstract
Acknowledgment
Overview
Topics
Reading outcomes
1: Introduction
2: Classification, structure, function, and regulation
3: Oncogenic activation of protein kinase
4: Kinase inhibitors
5: Challenges
6: Future prospects
7: Summary
References
Chapter 4: An insight on PI3K/AKT/MTOR inhibitors in cancer: Opportunity and translational perspectives
Abstract
1: Introduction
2: Significance of PI3K/AKT/mTOR pathway in cancer
3: Therapeutic indications of PI3K inhibitors and mTOR inhibitors available in market
4: Drug development in cancer therapy: Translational perspectives
5: Challenges in inhibition of PI3K/AKT/mTOR pathway
6: Conclusion and future perspective
References
Chapter 5: Recent advances in the therapeutic development of ERK inhibitors
Abstract
Conflict of interests
1: Introduction
2: ERK family members
3: ERK signaling in the cellular homeostasis
4: ERK in the pathophysiology of human diseases
5: Current status of ERK inhibitors
6: Mechanistic insights into ERK inhibition
7: Concluding remarks and future perspectives
References
Chapter 6: Emerging small-molecule inhibitors of ATM kinase targeting cancer therapy
Abstract
1: Introduction
2: Functions of ATM
3: Functionally interacting partners of ATM
4: Association of ATM with diseases
5: Inhibitors of ATM kinase
6: Clinical trials on ATM kinase inhibitors
7: Conclusion and outlook
References
Chapter 7: Targeting pyruvate kinase M2 signaling for development of effective cancer therapy
Abstract
1: Introduction
2: PKM2 regulation
3: PKM2 interactions in nucleus
4: PKM2 as a therapeutic target in cancer
5: PKM2 in cancer signaling
6: Mechanism of action of PKM2 inhibitors
7: PKM2 inhibitors in clinical trails
8: Conclusions and future prospects
References
Chapter 8: Serum and glucocorticoid-regulated kinase 1: A potential target for anticancer therapy
Abstract
1: Introduction
2: SGK1
3: SGK1 as a potential drug target
4: SGK1 structure
5: SGK1 inhibitors
6: Conclusion and future directions
References
Chapter 9: Akt inhibitors in cancer therapy
Abstract
1: Introduction
2: Akt structure and function
3: Akt is associated with malignant disease
4: Akt as a target for cancer therapy
5: Akt inhibitors
6: Conclusions and future directions
References
Chapter 10: Aurora kinase: An emerging potential target in therapeutics
Abstract
1: Introduction
2: Aurora kinase inhibitors (AKIs)
3: Association of Aurora kinases with diseases
4: AK dysregulation in the presence of pathogens and related diseases
5: Implications of inhibitors in the therapeutic management of disease
6: Conclusion and future perspectives
Conflict of interest
References
Chapter 11: The retroactive and future potentials of Aurora kinases in the treatment of cancer
Abstract
1: Introduction to Aurora kinase
2: Aurora kinase signaling pathway
3: Aurora-A small molecule inhibitors
4: Aurora-B small molecule inhibitors
5: Dual Aurora-A and Aurora-B small molecule inhibitors
6: PAN Aurora kinase inhibitors (Aurora-A, Aurora-B, and Aurora-C kinases inhibitors)
7: Summary and future prospects
References
Chapter 12: Targeting the altered tyrosine kinases in colorectal cancer: From inhibitors to drugs
Abstract
1: Introduction
2: Classification of protein kinase family
3: Kinome databases
4: Protein kinases as a therapeutic target in mCRC
5: Insights into multikinase inhibitors (MKIs)
6: Monoclonal antibodies as a blocker of tyrosine kinase activity
7: Receptor tyrosine kinases: Targeted therapeutic approach
8: Resistance to kinase inhibitors (KIs): A major problem
9: Potential protein kinases for future therapeutic purposes
10: Challenges and future directions
11: Concluding remarks
References
Chapter 13: PTEN-induced kinase1 (PINK1): More than just mitochondrial quality control
Abstract
1: Introduction
2: Expression and subcellular localization of PINK1
3: Gene structure and regulation
4: Protein sequence and 3D structure
5: Functional role of PINK1
6: Association of PINK1 with diseases
7: Therapeutic implications in cancer
8: Conclusion and future prospects
Conflict of interests
References
Chapter 14: ROCKs as a potential drug target to combat Alzheimer's disease
Abstract
1: Alzheimer's disease overview
2: Cytotoxic necrotizing factor 1
3: Rac 1 inhibitors
4: NSAIDs
5: Overview of ROCKS
6: Functions of ROCK
7: Controlling blood-brain barrier in AD through ROCKs
8: Controlling neuroinflammation in AD through ROCK inhibition
9: Neuroprotection and neuroregeneration of AD through ROCK inhibition
10: Protection of dendritic spines in AD through ROCK inhibition
11: ROCK in mouse model of AD
12: Future challenges
13: Conclusion
References
Chapter 15: Protein kinase inhibitors from discovery to therapeutics
Abstract
1: Introduction
2: Structures and isoforms of PDK
3: Isoforms of PDK
4: Expression and transcriptional regulation of PDKs and their relevance in disease therapy
5: Efficacy study of PDK inhibitors
6: Future of PDK inhibitors
References
Chapter 16: Polo-like kinases: An antimitotic drug target for cancer therapy
Abstract
1: Introduction
2: The PLK family
3: Molecular architecture of PLK1
4: Functions of PLK1
5: Mechanism and regulation
6: PLK1 expression and cancer
7: PLK1 inhibitors
8: Conclusion
References
Chapter 17: Src kinase: An attractive therapeutic target for prostate cancer
Abstract
Acknowledgment
1: Introduction
2: Structure and physiological functions of Src kinase
3: Src kinase and signaling pathways
4: Role of Src kinase in prostate cancer
5: SFK inhibitors and their pharmacological effects
6: Conclusions and future directions
References
Chapter 18: Kinase inhibition in Alzheimer’s disease
Abstract
1: Introduction
2: Kinases involved in tau phosphorylation
3: Kinases involved in APP phosphorylation
4: Implications of tau phosphorylation
5: Implications of Aβ phosphorylation
6: Protein kinase inhibitors in Alzheimer's disease
7: Conclusion, future prospects, and challenges
References
Chapter 19: Therapeutic targeting of glycogen synthase kinase-3: Strategy to address neurodegenerative diseases
Abstract
1: Introduction
2: Structural features of GSK-3
3: Association of GSK-3 with neurodegenerative diseases
4: GSK-3 and cell signaling
5: GSK-3 inhibitors
6: GSK3 inhibitors: Clinical status
7: Future prospective and challenges
8: Conclusions
References
Chapter 20: Microtubule affinity regulating kinase 4: A potential drug target from cancers to neurodegenerative diseases
Abstract
Acknowledgments
1: Introduction
2: MARK4 in human diseases
3: Structural features of MARK4 and strategies for designing MARK4 inhibitors
4: Current MARK4-focused therapeutic strategies
5: Conclusion and perspectives
References
Chapter 21: Receptor tyrosine kinase-like orphan receptors ROR1/2: Insights into the mechanism of action, inhibition, and therapeutic potential
Abstract
Acknowledgment
1: Introduction
2: Structural characteristics of ROR proteins ROR1 and ROR2
3: Expression analysis and biological implications in human disease
4: ROR1/2 as potential targets in human cancer
5: ROR1 inhibitors
6: ROR2 inhibitors
7: Conclusion
References
Chapter 22: Therapeutic potential of leucine-rich repeat kinase 2 inhibitors for Parkinson's disease treatment
Abstract
Acknowledgment
1: Introduction
2: Domain organization in LRRK2
3: LRRK2 as a modulator of signaling pathways
4: Mutations in LRRK2 and their impact on PD pathogenesis
5: Inhibitors of LRRK2 and their pharmacological effects
6: Assays for screening LRRK2 inhibitors
7: Conclusions and future directions
References
Chapter 23: Calcium calmodulin-dependent protein kinase as a potential drug target
Abstract
1: Introduction
2: Pathological role of CaMKII
3: CaMKII inhibitors
4: Conclusion and future perspectives
References
Chapter 24: Therapeutics of platelet-derived growth factor and signaling in different organs
Abstract
1: Introduction
2: Tyrosine kinase
3: PDGF structure
4: PDGF in physiology
5: PDGFR signaling
6: PDGF signaling in organogenesis
7: Skin
8: Testis
9: Kidney
10: Lens
11: Recent advances in drugs targeting platelet-derived growth factor
12: Potential inhibitors in preclinical and clinical trials for the PDGF kinases
13: Conclusive remarks
References
Chapter 25: EGFRC797S mutation and fourth-generation EGFR tyrosine kinase inhibitors
Abstract
1: Introduction
2: EGFR C797S mutation
3: Fourth-generation EGFR-TKIs
4: In vitro activities and in vivo efficacy of next-generation EGFR-TKIs
5: Clinical status of EGFR-TKIs
6: Prospects and challenges
References
Further reading
Chapter 26: Bacterial histidine kinases as potential antibacterial drug targets
Abstract
1: Introduction
2: HKs in bacterial resistance
3: HKs as potential antibacterial drug targets
4: Structures and signaling mechanism of histidine kinases
5: Conclusion
6: Future prospects
References
Chapter 27: Bacterial protein kinases: A target to inhibit the bacterial infections
Abstract
Acknowledgment
1: Introduction
2: Serine/threonine protein kinases
3: Protein tyrosine kinase
4: Bacterial arginine kinase
5: Histidine kinase
6: Targeting bacterial kinases as therapeutics
7: Conclusion
References
Chapter 28: Nanotechnology-based targeted delivery systems for protein kinase inhibitors in Cancer therapy
Abstract
1: Introduction
2: Nano-delivery for protein kinase inhibitors
3: Conclusion
References
Index

Life Sciences

Physical Sciences & Engineering

Social Sciences & Humanities

Health

Protein Kinase Inhibitors

From Discovery to Therapeutics

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Md. Imtaiyaz Hassan

Saba Noor