Meet the editors

Dr Vishwanath Gaitonde is currently appointed as a Senior Research Scientist at Cambrex High Point, NC, USA, where he designs, develops, and optimizes chemical processes for multi-kilo scale cGMP and nGMP production campaigns to support clinical trials in Phase I – Phase III. Prior to joining Cambrex, Dr Gaitonde was engaged in optimization of a lead molecule targeting broad spectrum viral respiratory disease in the Antiviral Me-

dicinal Chemistry Department, GlaxoSmithKline, NC, USA. Dr Gaitonde's PhD research was focused on the development of carbohydrate-based molecules as biochemical tools to probe the Mycobacterium tuberculosis GlgE mechanistic aspect. Additionally, his PhD research involved development of a novel amorphous polyester material based on sustainable chemistry.

Dr Partha Karmakar is currently appointed as a Research Scientist at the Washington University School of Medicine where his research involves development of a new therapeutic strategy for cancer treatment including development of small molecules and bioconjugates probes and an in-vitro and in-vivo efficacy study emphasizing clinical translation. Dr Karmakar was previously engaged in development and optimization of a lead molecule

targeting the bacterial colony growth mechanism in the Antibacterial Drug Discovery Department at GlaxoSmithKline – PA, USA. Dr Karmakar's PhD research involved development of glycopeptide-based vaccines and their in-vivo immunological evaluation.

Dr Ashit Trivedi is currently appointed as a Scientist in the Clinical Pharmacology Modeling and Simulations group at Amgen, USA, where his research work is extended into different therapeutic areas including oncology and neurosciences with a focus in cardiovascular diseases. As a clinical pharmacologist, Dr Trivedi participates in multifunctional study teams to design and conduct clinical pharmacology studies to support the global reg-

istration of pipeline drugs, perform PK and exposure-response analysis to inform dose selection, summarize and interpret PK, PK/PD, and clinical pharmacology results for internal/external presentations, study reports, and regulatory documents and interact with the line-management and different functions to implement strategies for drug label.

Contents

**Section 1**

**Section 2**

**Section 3**

*and Rossana C. Zepeda*

and Recent Applications

*and Grace Chitima Mugumbate*

*Iris Feria-Romero and Sandra Orozco-Suarez*

in Healthy Volunteers

*and Thales Kronenberger*

**Preface III**

Introduction **1**

**Chapter 1 3**

Computational Chemistry Advances in Modern Day Drug Discovery **11**

**Chapter 2 13**

**Chapter 3 27**

**Chapter 4 49**

Current View towards Pharmacokinetics in Drug Discovery **69**

**Chapter 5 71**

**Chapter 6 85**

Introductory Chapter: The Modern-Day Drug Discovery *by Partha Karmakar, Ashit Trivedi and Vishwanath Gaitonde*

Molecular Docking in Modern Drug Discovery: Principles

*by Aaftaab Sethi, Khusbhoo Joshi, K. Sasikala and Mallika Alvala*

Computational Deorphaning of *Mycobacterium tuberculosis* Targets *by Lorraine Yamurai Bishi, Sundeep Chaitanya Vedithi, Tom L. Blundell* 

Revisiting Pharmacokinetics and Pharmacogenetics of Methadone

ADME Profiling in Drug Discovery and a New Path Paved on Silica *by Arne Krüger, Vinicius Gonçalves Maltarollo, Carsten Wrenger* 

*by Natalia Guevara, Marianela Lorier, Marta Vázquez, Pietro Fagiolino,* 

Past, Present, and Future of Molecular Docking *by Thuluz Meza Menchaca, Claudia Juárez-Portilla* 

## Contents



Preface

Prevention and cure cases from various diseases reach a billion individuals every year. This is possible due to the organized efforts in the drug discovery program across the world led by pharmaceutical companies and academic institutions. Nevertheless, the majority of deaths globally are attributed to heart disease, stroke, pulmonary disease, lower respiratory infections, Alzheimer's, cancer, diabetes, and tuberculosis. One common aspect of these disease conditions is that they are preventable to some extent and a comparatively better quality of life can be provided to the patients with proper and timely treatment. To surmount this challenge, the drug discovery programs have advanced significantly in the past decade. This book, "Drug Discovery and Development – New Advances", brings together some of the recent progress in the field through the complex process, starting with computational modeling right through launching a drug in the market. The book aims to provide expert opinions and experiences from researchers encompassing diverse key topics critical in drug discovery and development. Case studies of some selected disease conditions will showcase the challenges and burdens faced by the pharmaceutical industries. The book covers the latest advances in molecular docking, pharmacokinetics, and new therapeutic options of some rare diseases along with pediatric drug discovery and development. Overall, the book represents a view

of the complex fabric of the modern-day drug discovery program.

**Dr. Vishwanath Gaitonde** Senior Research Scientist,

Cambrex High Point, Inc., High Point, NC, USA

> **Partha Karmakar** Research Scientist,

> > **Ashit Trivedi**

USA

USA

Department of Chemical Research and Development,

Clinical Pharmacology Modeling and Simulations Group at Amgen,

Washington University School of Medicine,
