Medicinal Chemistry Reviews

Volume 52, Chapter 13

Beyond PARP:  Inhibitors of DNA Repair Processes as Potential Therapeutic Agents for Cancer

Allan Michael Jordan and Kate Mary Smith

1.          Introduction                                                                                                               244

            1.1        The DNA Damage Response (DDR) in Cancer—Complexity and

Redundancy                                                                                                   244

            1.2        Exploiting the DDR to Date—the PARP Inhibitors                                                245

            1.3        Challenges for Drug Discovery                                                                     245

                        1.3.1     Druggability of Emerging Target Classes                                         245

                        1.3.2     Biological and Screening Challenges                                              246

2.         DDR-Related Kinases                                                                                                247

            2.1        ATM and ATR Kinases—Similarities and Differences                                247

            2.2       ATM Inhibitors                                                                                               248

            2.3       ATR Inhibitors                                                                                                249

            2.4       Clinical Progression                                                                                      251

3.         Exploiting Compromised DDR via Wee1 Kinase                                                    252

            3.1        Wee1 Inhibitors                                                                                             252

            3.2       Single Agent vs. Combination Studies Reveal Novel Therapeutic

Options                                                                                                          253

            3.3       Clinical Progression                                                                                      254

4.         PARG Inhibitors                                                                                                         254

            4.1        The Role of PARG                                                                                          254

            4.2       PARG Inhibitors                                                                                             255

            4.3       Clinical Implications                                                                                      256

5.         Future Directions and Conclusions                                                                          257

To purchase a copy, contact secretary@acsmedchem.org

ACS Division of Medicinal Chemistry

Webmaster:  secretary@acsmedchem.org