Contemporary Accounts in Drug Discovery and Development

11 Chapter 12Figure 12.1 Peptide science milestones. Macrocyclic peptides are highlighted...Figure 12.2 Structures of macrocyclic peptides insulin, oxytocin, somatostat...Figure 12.3 Structures of α‐melanocyte‐stimulating hormone (α‐MSH) and macro...Figure 12.4 Structures of macrocyclic peptides linaclotide, zilucoplan, a PC...Figure 12.5 Structure of macrocyclic peptide BCY12491 highlighting its CD137...Figure 12.6 Structures of macrocyclic peptides cyclosporin A, a XIAP‐BIR3 in...Figure 12.7 Structures of cell‐permeable macrocyclic peptide “prodrug” of CA...Figure 12.8 Structures of macrocyclic peptides ATSP‐7041 and dPMI‐d(1–5‐12) ...Figure 12.9 Multidisciplinary paradigm for macrocyclic peptide drug discover...

12 Chapter 13Figure 13.1 (a) Anthramycin (PBD monomer), (b) PBD core structure, and (c) i...Figure 13.2 (a) Structure of SJG‐136 binding with DNA. (b) Interstrand cross...Figure 13.3 The SAR of the PBDs: (a) monomers, (b) dimers, and (c) unsymmetr...Figure 13.4 Non‐site‐specific and site‐specific PBD‐ADCs conjugations.Figure 13.5 SG‐3199 (payload), SG‐3249 (linker‐payload), and SG‐3199 ADC.Scheme 13.1 Synthesis of SG‐3249. Reagents and conditions: (a) Alloc‐Cl, pyr...Figure 13.6 The structures of ADCT‐601 and its ADCs.Figure 13.7 SGD‐1882 payload, the payload‐linker SGD‐1910 (Talirine), and SG...Scheme 13.2 Synthesis of SG‐1882. Reagents and conditions: (a) Ac 2O, pyridin...Scheme 13.3 Synthesis of IGN462 and IMGN779. Reagents and conditions: (a) 3‐...Scheme 13.4 Synthesis of IGN549, IMGN632, and TAK164. Reagents and condition...Figure 13.8 IMGN779 and its ADCs.Figure 13.9 IMGN632 and its ADCs.Figure 13.10 TK‐164 and its ADCs.Figure 13.11 Pyrridinobenzodiazepines.Figure 13.12 D212 and its ADCs.Figure 13.13 PBD‐duocarmycin dimer ADCs.Figure 13.14 PBD dimer with thio‐oxophosphane ADC.Figure 13.15 Oxazolidine pro‐PBD as latent payload [91].Figure 13.16 The model release study of oxazolidine pro‐PBD.Figure 13.17 Pro‐PBD SMDC (EC2629).Scheme 13.5 Synthesis of EC2629. Reagents and conditions: (a) ethanolamine, ...Figure 13.18 Oxime ether pro‐PBD as latent payload.Scheme 13.6 Synthesis of SMDC2. Reagents and conditions: (a) 6‐1, iPr 2Figure 13.19 Increasing the therapeutic index from (a) by cytotoxic drugs to...Figure 13.20 An exposure‐centric approach to TI determination in humans [108...Figure 13.21 β‐Glucoronide prodrug of PBD dimer ADCs (SG3600 ADC).

13 Chapter 14Figure 14.1 Two‐dimensional isobologram based on Loewe's additivity model sh...Figure 14.2 Three‐dimensional isobologram illustrating drug combination data...Figure 14.3 Synthetic lethality of PARP inhibitor in BRCA‐deficient cells.Figure 14.4 Structures of representative PARP inhibitors.Figure 14.5 Representative drugs from different generations of cephalosporin...Figure 14.6 The mechanism of class A, B, C, and D β‐lactamase catalyzed hydr...Figure 14.7 Structures of β‐lactamase inhibitors.Figure 14.8 The mechanism of inactivation of β‐lactamases by avibactam.

14 Chapter 15Figure 15.1 Graphic illustration of bench and bedside in connection with tra...Figure 15.2 Optimal bidirectional interactions between the four phases of tr...Figure 15.3 Cartoon of the major components of the COVID virus.Figure 15.4 The estimated best timeframes for the application of the PCR, an...Figure 15.5 Life cycle of SARS‐CoV‐2 in host cells.Figure 15.6 Structures of remdesivir, parent of remdesivir GS‐441524, interm...Figure 15.7 Schematic illustration of typical vaccine development stages and...Figure 15.8 Chemical structure of dexamethasone.

1 Cover Page

2 Title Page Contemporary Accounts in Drug Discovery and Development Edited by Xianhai Huang InventisBio Co., Ltd., Florham Park, USA Robert G. Aslanian New Jersey City University, Jersey City, USA Wayne H. Tang Schrödinger Inc., New York, USA

3 Copyright Page

4 Preface

5 List of Contributors

6 Table of Contents

7 Begin Reading

8 Appendix A Monoclonal Antibody Drug Discovery and Development Paradigm

9 Appendix B Glossary

10 Appendix C Abbreviations

11 Index

12 WILEY END USER LICENSE AGREEMENT

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