Current Molecular Targets of Heterocyclic Compounds for Cancer Therapy / Vivek Asati and Ankur Vaidya, editors.

Format:

Book

Contributor:

Asati, Vivek, editor.

Vaidya, Ankur, editor.

Language:

English

Subjects (All):

Chemistry, Organic.

Neoplasms--therapy.

Heterocyclic Compounds--antagonists & inhibitors.

Molecular Targeted Therapy.

Medical Subjects:

Neoplasms--therapy.

Heterocyclic Compounds--antagonists & inhibitors.

Molecular Targeted Therapy.

Physical Description:

1 online resource (504 pages)

Edition:

First edition.

Place of Publication:

San Diego, CA : Elsevier Inc., [2024]

Summary:

Current Molecular Targets of Heterocyclic Compounds for Cancer Therapy discusses recently developed treatments based on molecular targets which are genetically altered in cancer cells and are essential for tumor development and survival.

Contents:

Front Cover

CURRENT MOLECULAR TARGETS OF HETEROCYCLIC COMPOUNDS FOR CANCER THERAPY

Copyright

Dedication

Contents

Contributors

Preface

Acknowledgments

1 - Activin receptor-like kinase-2 inhibitors

1. Introduction

2. Structure and types of ALK2

3. ALK2 signal transduction

4. Physiological role of ALK2

5. Disorders associated with ALK2

5.1 Fibrodysplasia ossificans progressiva

5.2 Diffuse intrinsic pontine glioma

5.3 Diffuse idiopathic skeletal hyperostosis

6. ALK2 inhibitors

7. Conclusions

References

2 - Ataxia telangiectasia and Rad3-related protein inhibitors

2. ATM and ATR in relation to DNA damage response

3. Structure of the ataxia telangiectasia-mutated and Rad3-related checkpoints

4. Etiological association of ATM and ATR in precipitating cancer in at patients

5. Heterocyclics used for inhibiting ATM and ATR

5.1 Caffeine

5.2 Wortmannin

5.3 Schisandrin B

5.4 NU6027

5.5 NVP-BEZ235 and ETP-46464

5.6 Torin-2

5.7 VE-821

5.8 AZ20

5.9 Azabenzimidazole

6. ATM and ATR inhibitors currently under clinical trial

6.1 Berzosertib

6.2 M6620 (VX-970)

6.3 Ceralasertib

6.4 BAY1895344

6.5 Camnosertib

7. Closing statement

Further reading

3 - Breakpoint cluster region Abelson kinase inhibitors

2. BCR-AbL

2.1 Structure and function

2.2 Inhibitors of BCR-AbL

2.2.1 First-generation inhibitor

Imatinib

2.2.1.1 Mechanisms of resistance to imatinib

2.2.2 Second-generation inhibitors

2.2.2.1 Phenylamino-pyrimidine derivative: Nilotinib (Fig. 3.3)

2.2.2.2 Thiazole carboximide derivative: Dasatinib

2.2.2.3 Quinolone derivative: Bosutinib

2.2.3 Third generation inhibitors.

2.2.3.1 Imidazo-benzamide derivative: Ponatinib

2.2.3.2 Pyrazo-pyrimidine derivative: Asciminib

3. Conclusions

Declaration of interests

4 - Casein kinase (CK) inhibitors

2. Protein kinase CK1

2.1 Structures and function

2.2 Inhibitors of protein kinase CK1

2.2.1 Bicyclic scaffold inhibitors

2.2.1.1 Isoquinoline and indolinone derivatives

2.2.1.2 Benzimidazole and indazole derivatives

2.2.1.3 Benzothiazole derivatives

2.2.1.4 Purine and purine-like derivatives

2.2.2 Monocyclic scaffold inhibitors

2.2.2.1 Imidazole and isoxazole derivatives

2.2.2.2 Pyrazole derivatives

2.2.3 Tricyclic scaffold inhibitors and others

3. Protein kinase CK2

3.1 Structures and function

3.2 Inhibitors of protein kinase CK2

3.2.1 Bicyclic scaffold inhibitors

3.2.1.1 Polyhalogenated benzimidazole and benzotriazole derivatives

3.2.1.2 Pyrazolo-triazine and pyrazolo-pyrimidine derivatives

3.2.1.3 Flavonoid derivatives

3.2.2 Tricyclic scaffold inhibitors

3.2.2.1 Benzonaphthyridine derivatives

3.2.2.2 Anthraquinone and coumarin derivatives

3.2.3 Monocyclic scaffold inhibitors

3.2.3.1 2-Amino aromatic heterocyclic derivatives

3.2.3.2 Phenyl-based derivatives

3.2.4 Tetracyclic scaffold inhibitors and others

4. Protein kinase Fam20C

4.1 Structures and function

4.2 Inhibitors of protein kinase Fam20C

5. Conclusions

5 - Recent updates on c-Src kinase and Src-Abl nonreceptor tyrosine kinases inhibitors

1.1 Structural features of c-Src kinase and Src-Abl

1.1.1 Conserved domain structure

1.1.2 N-terminal myristoylation site: Covalent attachment and membrane anchoring

1.1.3 SH3 domain: Mediating protein-protein interactions through proline recognition.

1.1.4 SH2 domain: Facilitating protein-protein interactions via phosphotyrosine recognition

1.1.5 Tyrosine kinase domain: Catalytic activity and substrate binding

2. Phosphorylation and dephosphorylation: Regulation of c-Src kinase activity

2.1 Intramolecular interaction between SH2 domain and C-terminal phosphorylated tyrosine

2.2 Disruption of the inactive state: Dephosphorylation and ligand binding

2.3 Activation mechanisms and implications for cellular signaling

3. Src-Abl: Fusion protein and leukemia connection

3.1 There are various chemical categories of inhibitors that target c-Src kinase and Src-Abl, modulating their activity and sho ...

3.1.1 ATP-competitive inhibitors

3.1.2 Allosteric inhibitors

3.1.3 Peptide substrate-based inhibitors

3.1.4 Covalent inhibitors

3.2 Miscellaneous

6 - Cyclin-dependent kinase 4 and 6 in cancer: Exploration of CDK4/6 inhibitors as anticancer agents

2. Different types of CDKs

3. Regulation by CDKs in cancer

3.1 CDK4

3.2 CDK6

4. Structure-activity relationship for the already reported CDK 4/6 inhibitors

7 - Impact of epidermal growth factor receptors as a key clinical target against cancer

2. Conclusion

8 - Cancer and insulin-like growth factor inhibitors: Recent advancements and SAR analysis

2. Insulin-like growth factors

3. Involvement of IGFs/IGFR in various diseases

4. Role of IGF in cancer

5. Clinical developments for IGFs

6. Recent development targeting IGFR

7. Conclusion

9 - Mitotic kinesin spindle protein (KSP/Eg5 ATPase) inhibitors

1.1 Mitotic kinesin biology

1.2 Kinesin structure and function

2. Kinesin spindle protein inhibitors

2.1 Monastrol

2.2 S-trityl-l-cysteine.

2.3 Beta carboline

2.3.1 Tetrahydro-β-carbolines

2.4 Ispinesib and related compounds

2.4.1 Quinazolinone core replacement

2.5 Chromen-4-one derivatives

2.6 Dihydropyrrole and dihydropyrazole derivatives

2.7 Tetrahydroisoquinoline compounds

3. Conclusion

4. Summary and future outlook

Abbreviation

10 - p21-Activated kinase 1 inhibitors

2. PAK1 structure and regulation

3. PAK1 role in cancer

3.1 PAK1 in cancer drug resistance

4. PAK1 inhibitors

4.1 ATP competitive PAK1 inhibitors

4.1.1 Oxindole/maleimide derivatives

4.1.2 Pyrazoles

4.1.3 Pyrimidines

4.1.4 Azaindole

4.1.5 Other ATP-competitive inhibitors

4.2 Allosteric PAK1 inhibitors

4.3 Treatment combinations with PAK inhibitors

4.4 Natural products

5. Conclusion

11 - p38 mitogen-activated protein kinase inhibitors

2. MAPK types and signal transduction

2.1 Extracellular signal-regulated kinases

2.2 c-Jun N-terminal kinases

2.3 p38 mitogen-activated protein kinases

3. FDA-approved MAPK inhibitors

3.1 FDA-approved BRAF inhibitors

3.1.1 Sorafenib

3.1.2 Regorafenib

3.1.3 Vemurafenib

3.1.4 Dabrafenib

3.1.5 Encorafenib

3.2 FDA-approved MEK inhibitors

3.2.1 Trametinib

3.2.2 Cobimetinib

3.2.3 Binimetinib

3.2.4 Selumetinib

4. Mechanisms of resistance

4.1 Mechanisms of primary resistance

4.2 Mechanisms of secondary resistance

4.2.1 MAPK-pathway reactivation

4.2.2 RTKS hyperactivation

4.2.3 Analogous signaling pathways (PI3K/STAT/Hippo) activation

4.2.4 Cellular transformation and transcriptional factors

4.2.4.1 MITF

4.2.4.2 ZEB1 (zinc finger E-box binding homeobox 1)

5. Therapeutic strategies to overcome MAPK resistance

5.1 Combination therapy for targeting many proteins/pathways.

5.1.1 Targeting parallel pathways (PI3K/AKT/mTOR/Hippo)

5.1.2 Targeting RTKs

5.1.3 Targeting ZEB1 with MAPK

5.1.4 Targeting BCL-XL with MAPK

5.2 Single inhibitor to block multiple pathways

5.3 Combining immunotherapeutic agents with MAPK-inhibitors

6. The future of MAPK inhibitors therapeutics

7. Summary and future outlook

12 - Proviral integration site for Moloney murine leukemia virus-1 (PIM-1) kinase inhibitors

2. Structure of PIM-1

3. Physiological functions of PIM-1

4. Functional relevance of PIM-1 in carcinomas

4.1 Colon carcinoma

4.2 Bladder cancer

4.3 Cervical cancer

4.4 Pancreatic cancer

4.5 Prostate cancers

5. PIM-1 kinase inhibitors

5.1 Natural compounds

5.2 Quercetagetin

5.3 Hispidulin

5.4 Tetrazine derivatives

5.5 Pyrazole derivatives

5.6 Diaminopyrazole

5.7 Phenanthridines derivatives

5.8 Pyridine derivatives

5.9 Pyridinamines derivatives

5.10 Imidazo[1,2-b]pyridazines

5.11 Pyrimidine derivatives

5.12 Pyrazolopyrimidine derivatives

5.13 Pyrazolopyridines

5.14 Pyrazolo quinazoline derivatives

5.15 Pyran derivatives

5.16 Quinoline derivatives

5.17 Quinoxaline derivatives

5.18 Oxazine derivatives

5.19 Oxindole derivative

5.20 2-Azaindole (indazole) derivatives

5.21 3,5-disubstituted 6-azaindazoles

5.22 Quinazolinone-pyrrolopyrrolones

5.23 Quinoxaline-pyrrolodihdropiperidinones

5.24 Thiazole derivative

5.25 Thiazolidine-2,4-dione

5.26 Thiophenes derivatives

5.27 Thienopyridines

5.28 Triazine derivatives

5.29 Triazole derivatives

5.30 Imidazo[1,2-b]pyridazine

5.31 Triazolo[4,5-b]pyridines

5.32 Benzofuropyrimidinones derivatives

5.33 Pyrrolo-carbazole derivatives

5.34 Benzodiazocine derivative

5.35 Indole derivatives

5.36 Oxadiazole derivatives.

5.37 Pyrazine derivatives.

Notes:

Includes bibliographical references and index.

Description based on publisher supplied metadata and other sources.

Description based on print version record.

ISBN:

0-323-99632-9

OCLC:

1432600768