Over the years, India has attained a prominent global position in the manufacture of Generic Drugs. This success can be attributed to its synthetic organic chemistry and chemical engineering strengths, nurtured by the timely policies of the Government of India. However, breakthrough successes in New Drug Discovery have remained elusive, despite the brilliant and sustained efforts of many Indian researchers and Pharma establishments. The Indian National Science Academy thought it appropriate to document India’s New Drug Discovery Research (NDDR) journey to date. Gathering contributions from prominent researchers in the Indian Pharma Industry and Academia, this book highlights their efforts, achievements, and the status quo of Indian NDDR.
Erscheinungsdatum: 11.02.2021

lgli/P:\springer_dnd140621\springer/10.1007%2F978-981-15-8002-4.pdf

nexusstc/Drug Discovery and Drug Development: The Indian Narrative/85a845bca70a5f03659c281fc5370a86.pdf

lgrsnf/2021_Book_DrugDiscoveryAndDrugDevelopmen.pdf

scihub/10.1007/978-981-15-8002-4.pdf

zlib/Science (General)/Madhu Dikshit/Drug Discovery and Drug Development: The Indian Narrative_15357711.pdf

Harald Nahrstedt

Dikshit, Madhu

Springer Nature Singapore Pte Ltd Fka Springer Science + Business Media Singapore Pte Ltd

Singapore, Singapore

6, 20210210

lg3017049

producers:
Adobe PDF Library 10.0.1

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Foreword
Preface
About the Book
Contents
About the Editor
1: Traditional Medical System (TMS) for Sustainable Healthcare in India
1.1 Introduction to Global Trends in Traditional Medical System (TMS)
1.2 Impact of TMS on Sustainable Healthcare
1.2.1 Sustainability in Traditional Medical Practice
1.2.2 Sustainable Healthcare in Ayurveda
1.3 Ayurveda-Traditional System of Medicine in India
1.4 Role of TMS in Health Care
1.4.1 Role of National Rural Health Mission
1.4.2 Changing Scenario of TMS in Health Care
1.4.3 Management and Technical Strengthening
1.4.4 Major Gaps and Technical Assistance Needs
1.5 Conservation of Traditional Knowledge
1.6 Validation of Traditional Medicine
1.6.1 Chemo-Profiling and Standardization of Traditional Medicine
1.6.2 Plant Metabolomics
1.7 Quality Assurance of Herbal Medicine
1.7.1 Classical Systematics in Species Authentication and the Utility of Good Agricultural and Collection Practice (GACP)
1.7.2 Genomic Profiling and DNA Barcoding in Species Authentication
1.7.3 Macroscopic and Microscopic Characterization of Sorted Plant Materials
1.7.4 Phytochemical Profiling of Plant Parts as a Tool for Identification and Characterization
1.7.5 Guidelines for Good Plant Authentication and Identification Practice (GPAIP)
1.7.6 Assurance of the `Purity ́ of Botanical Raw Materials: Impurity Profiling
1.8 Pharmaceuticals, Nutraceuticals, Phyto-Pharmaceuticals Inspired from Ayurveda
1.9 Global Harmonization and Regulatory Status of Traditional Medical Systems (TMS)
1.10 Clinical Trial and Pharmacovigilance of TM
1.10.1 Geriatric Diseases
1.10.1.1 Alzheimer ́s Disease and Cognition Deficit
1.10.1.2 Parkinson ́s Disease
1.10.2 Metabolic Diseases
1.10.2.1 Diabetes
1.10.2.2 Hypertension and Associated Cardiovascular Diseases
1.10.2.3 Osteoporosis
1.10.3 Infectious Diseases
1.10.3.1 Tuberculosis
1.10.3.2 Malaria
1.10.3.3 Leishmaniasis
1.10.3.4 Acquired Immunodeficiency Syndrome
1.10.4 Inflammatory Diseases
1.10.4.1 Chronic Obstructive Pulmonary Disease
1.10.4.2 Rheumatoid Arthritis and Osteoarthritis
1.10.5 Cancer
1.10.5.1 Breast Cancer
1.10.5.2 Lung Cancer
1.10.5.3 Prostate Cancer
References
2: Modern Drug Discovery and Development for TB: The India Narrative
2.1 Approaches to TB Drug Discovery: The Past and the Present
2.1.1 A Historical Perspective of the TB Drug Regimen
2.2 TB Drug Discovery: Past and Present-A Perspective
2.2.1 The Modern Day Drug Discovery Process
2.2.2 Hit Identification
2.2.3 Lead Identification
2.2.4 Lead Optimization (LO)
2.2.5 Challenges of Anti-Mycobacterial Chemistry and Progressing Leads into Clinical Candidates
2.2.6 Newer Therapeutic Approaches
2.3 A Paradigm Shift in TB Drug Therapy: Finding New Combinations
2.4 Global and India Efforts on TB Drug Discovery
2.5 Going Forward: TB Drug Discovery and India
2.5.1 European Union Framework 6 and 7 Projects
2.5.2 TB Accelerator Programme
2.6 Closing the Loop
References
3: Indian Discovery Effort in the Quest of Novel Antibiotics
3.1 Background
3.2 Need for Antibacterial Drug Discovery and Development
3.3 Antibacterial Discovery and Development in India
3.3.1 Hindustan Antibiotics Limited
3.3.2 Hoechst India Limited
3.3.3 Ranbaxy Laboratories
3.3.4 Dr Reddy ́s Laboratory
3.3.5 Nicholas Piramal
3.3.6 Orchid Pharma
3.3.7 Aurigene
3.3.8 Bugworks
3.3.9 Zydus Cadila
3.3.10 Vitas Pharma
3.3.11 Vyome Bioscience
3.3.12 Panacea Biotech
3.3.13 Central Drug Research Institute
3.3.14 Wockhardt Limited
3.3.14.1 1,6-Diaza-Bicycly-spiro[3.2.1] Octanes beta-Lactam Enhancers
3.4 Elements of Success in Wockhardt ́s Discovery Program
3.4.1 Scientific Freedom, Access to Resources and Organizational Capabilities
3.4.2 Team Building and Right Sizing
3.4.3 Understanding Gold Standard Antibiotics
3.4.4 Dynamics Between Classes of Antibiotics and Territorial Preference
3.4.5 Differentiating Product Profile for Unmet Medical Needs
3.4.6 Blending the Role of Experts and CROs with Internal Expertise
3.4.7 The Role of Discovery Team in Supporting Clinical Development
3.4.8 Long-Term Engagement by Top Management
3.4.9 De-risking Projects
3.5 Urgency to Expand Antibiotic Discovery Initiatives in India
3.6 The Way Forward
References
4: New Drug Discovery and Development in India to Counter Malaria
4.1 Introduction
4.2 Antimalarials: The India Story
4.2.1 α/beta Arteether: A Successful Intervention for Complicated Malaria
4.2.2 Primaquine Derivative Elubaquine/Aablaquine for P. vivax
4.2.3 Synthetic Endoperoxides
4.2.4 Exploration of Leads from Traditional Knowledge
4.2.5 Formulations
4.3 Exploring New Biological Targets for Drug Discovery and Design
4.3.1 Fatty Acid Synthesis (FAS-II Pathway)
4.3.2 Aminoacyl tRNA Synthetases
4.3.3 DNA Gyrases
4.3.4 Noncanonical Structures at Telomeric Ends
4.3.5 ATP Transporters
4.3.6 Heme Biosynthesis and Detoxification Pathways
4.3.7 Proteases/Disaggregases
4.3.8 Other Unique Pathways/Targets
4.4 Repositioning of Molecules for Antimalarial Activity
4.5 Gaps and Future Measures
References
5: Modern Drug Discovery and Development in the Area of Leishmaniasis
5.1 A Brief Introduction About the Disease and the Causative Agent
5.2 Global Distribution and Status of the Disease in India
5.3 Elimination Program in India and Its Challenges
5.4 Present Chemotherapy and Its Limitations
5.4.1 Combination Therapy
5.5 Discovery of New Chemical Entities for Antileishmanial Chemotherapy and Present Scenario of the Drug Pipeline
5.5.1 Pipeline (Leads Under Development)
5.5.1.1 Nitroimidazoles
5.5.1.2 Sitamaquine
5.5.1.3 Ravuconazole
5.5.1.4 Aminopyrazoles
5.5.2 Medicinal Chemistry Efforts to Identify New Chemical Compounds as Antileishmanials
5.6 Drugs in Use in New Delivery Systems
5.7 Role of Pharma Companies and Central Funding Agencies in Drug Discovery and Development Against VL
5.8 Challenges and Solutions
5.9 Conclusions
References
6: Introduction to Diabetes and Prevalence in India
References
7: Type 2 Diabetes Mellitus: Marketed Drugs and Mechanisms
7.1 Insulin Secretagogues: Drugs Which Trigger Insulin Release from Pancreatic beta-cells
7.1.1 Sulfonylureas (SU)
7.1.2 Meglinitides
7.2 Absorption Inhibitors
7.3 Biguanides
7.4 Insulin Sensitizers
7.5 Enhancing Glucose-Stimulated Insulin Secretion
7.5.1 GLP-1 Agonists
7.5.2 DPPIV Inhibitors
7.6 Selective Sodium-Glucose Transporter-2 Inhibitors
7.6.1 Unmet Medical Need in Metabolic Disorders and Way Forward
7.6.1.1 Adenosine Monophosphate Activated Kinase (AMPK): A Potential Target for Total Metabolic Disorders
7.6.1.2 Protein Tyrosine Phosphatase Inhibitors
7.6.1.3 Fructose-1,6-bisphosphatase (FBPase)
7.6.1.4 Phosphoenol Pyruvate Carboxykinase (PEPCK)
7.6.1.5 Free Fatty Acid Receptors (FFAR-1)
7.6.1.6 G-protein Coupled Receptors (GPCR)
7.6.1.7 Curing of the Disease: Vaccine Approach
7.6.1.8 Curing of the Disease: Formulated Indian Natural Products Approach
References
8: Anti-diabetes Research in India: Contributions from Industrial Organizations
8.1 Anti-diabetes Drug Discovery Effort in India
8.1.1 Contributions Made by Indian Pharma Companies
8.1.1.1 Dr. Reddy ́s Laboratories Limited
8.1.1.2 Zydus Cadila
8.1.1.3 Glenmark Pharmaceuticals
8.1.1.4 Orchid Chemicals and Pharmaceuticals
8.1.1.5 Panacea Biotec
8.1.1.6 Matrix Laboratories
8.1.1.7 Piramal Enterprises Ltd
8.1.1.8 Other Companies
8.2 Perspective of Current Anti-diabetes Research
8.2.1 Need for New Drugs Based on Existing/Novel Targets
8.2.1.1 Drawbacks of Common Anti-diabetes Drugs
8.2.1.2 Newer Goals of Anti-diabetes Research
8.2.2 Targets and Agents Currently Being Pursued Worldwide
8.2.2.1 G-Protein-Coupled Receptors
8.2.2.2 Glucokinase Activators
8.2.2.3 Triazine-Based Agent Imeglimin
8.2.2.4 New Incretin Mimetics
8.2.2.5 Inhibitors of SGLT2
8.2.2.6 Selective PPARγ Modulators
8.2.3 Current Scenario in India
8.2.3.1 Compounds Being Pursued
8.2.3.2 Quest for Global Partners
8.2.3.3 Role of Academic Institutions/National Laboratories
8.3 Future of Anti-diabetes Research in India and Way Forward
8.3.1 Refocusing and Restructuring Drug Discovery Efforts
8.3.2 Overcoming Other Barriers
8.4 Conclusions
References
9: Indian Academia Tryst with Cardio-metabolic Drug Discovery and Development
9.1 Introduction
9.1.1 Marketed Products
9.1.1.1 AYUSH-82/IME-9
9.1.1.2 BGR-34
9.1.1.3 D5 Chooranam
9.1.1.4 Picroliv
9.1.1.5 PMZ-2010 (Centhaquin)
9.1.1.6 Gugulipid
9.1.2 IND Stage and Pre-launch Molecules
9.1.2.1 S007-867
9.1.2.2 Curcuma Extract (HM)
9.1.2.3 CDR-267-F018
9.1.2.4 Novel Streptokinase
9.1.3 Molecules with Preliminary Studies
9.1.3.1 Dialyzed Fenugreek Seed Extract
9.1.3.2 Anti-diabetic Natural Product
9.1.3.3 Anti-atherosclerotic Polyherbal Formulation
9.2 Challenges in Developing Drugs from Natural Sources
9.3 Future Perspective
References
10: Modern Drug Discovery and Development in the Area of Cancer: Indian Context
10.1 What Is Cancer?
10.1.1 Whether Cancer Is a Disease of Humans?
Peto ́s Paradox
10.1.2 How Old Is Cancer?
10.2 Cancer Types and Incidence
10.3 Cancer in India
10.3.1 Role of Council of Scientific and Industrial Research, India
10.3.2 Role of Other Government Organizations
10.3.3 Predominant Cancer Types in India
10.4 Cancer Therapy
10.4.1 Drug Resistance in Cancer
10.5 Cancer Therapeutics: Indian Context
10.5.1 Generics
10.5.2 Contribution of Indian Pharmaceutical Sector
10.5.3 Contribution of Council of Scientific and Industrial Research, India
10.5.4 Biosimilars
10.5.5 Anticancer Drugs from Traditional System of Medicine
10.5.6 Contribution of CSIR Institute
10.5.7 Advances in Comprehensive Cancer Care in India
10.6 Modern Drug Discovery and Development in the Area of Cancer in India
10.7 Novel target for Cancer therapy
References
11: Biopharmaceutical Development in India: Recommendations on Collaboration and Innovation to Enable Affordable Healthcare
11.1 The Biopharmaceutical Industry Landscape
11.1.1 The Science of Biopharmaceuticals
11.1.2 The Business of Novel Biopharmaceuticals
11.1.3 The Science and Business of Biosimilars
11.2 The Advent of Indian Biopharmaceutical Industry
11.3 A Culture of Collaboration Is Essential for Innovation
11.3.1 Measuring Effective Collaboration
11.3.2 Factors for Successful Collaboration
11.3.3 Benefits of Collaboration
11.3.4 The Collaboration Report Card for India
11.3.4.1 Education and Training
11.3.4.2 Interdisciplinary Science and Technology
11.3.4.3 Micro-Environment
11.3.4.4 Macro-Environment
11.3.4.5 Translational Science
11.3.4.6 Regulatory Governance
11.4 Innovation Is Central to Transforming the Biopharmaceutical Industry
11.4.1 Innovation in Biopharmaceuticals
11.5 Recommendation for Policies in Biopharmaceuticals
11.5.1 Collection of Relevant Information
11.5.2 Evaluation of Opportunities
11.5.3 Establish Goals Through Government Initiatives
11.5.3.1 The Road Ahead
References
12: Regulatory Requirements and Quality Standards in India ́s Clinical Trials Journey
12.1 Background
12.2 Trigger for Growth of Clinical Research
12.3 Trigger for Revisiting Clinical Trial Regulations
12.4 Repercussions of Apex Court ́s Directives
12.5 Impact of the Three Major Regulatory Amendments
12.6 Regulatory Reforms Undertaken to Resurrect the Clinical Trial Sector
12.7 New Drugs and Clinical Trials Rules, 2019
12.8 Quality and Compliance in Clinical Trials
12.9 Going Forward
Bibliography
Websites Referred
13: New Drug Discovery and Development: Indian Pharmaceutical Industry
13.1 Introduction
13.1.1 Indian Pharma Companies
13.2 New Drug Discovery and Development: Indian Contributions
13.2.1 Brief History of Indian Contributions and Present Status
13.2.2 Drug Discovery Research in Indian Industry: Current Trends (from Recent Press Announcements)
13.2.3 Drug Discovery Research in Indian Industry: More Recent Strategies
13.3 Reasons for Slowing Down NDDR Across Indian Pharma Industry
13.3.1 Profits from Generics Business Inadequate to Support NDDR
13.3.2 Knowledge Gap
13.3.3 Resource Pressures Due to China Competition
13.3.4 Other Important Factors for Slowing Down NDDR
13.4 Enabling Measures to Boost NDDR in India
References

2021-05-31