Current status and future promise of next-generation poly (ADP-Ribose) polymerase 1-selective inhibitor AZD5305
The family of poly (ADP-ribose) polymerases (PARPs) consists of 17 members, which have been demonstrated as having effects on a series of cellular processes, including DNA replication and repair. PARP inhibitors (PARPi) suppress DNA repair through “PARP trapping”, thus, constitute an important treat...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-01-01
|
| Series: | Frontiers in Pharmacology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.979873/full |
| _version_ | 1797945484025790464 |
|---|---|
| author | Jingcao Zheng Jingcao Zheng Zhengyu Li Zhengyu Li Wenjiao Min |
| author_facet | Jingcao Zheng Jingcao Zheng Zhengyu Li Zhengyu Li Wenjiao Min |
| author_sort | Jingcao Zheng |
| collection | DOAJ |
| description | The family of poly (ADP-ribose) polymerases (PARPs) consists of 17 members, which have been demonstrated as having effects on a series of cellular processes, including DNA replication and repair. PARP inhibitors (PARPi) suppress DNA repair through “PARP trapping”, thus, constitute an important treatment option for cancer nowadays. In addition, PARP inhibition and homologous recombination repair (HRR) defects are synthetically lethal, giving a promising therapeutic for homologous recombination repair deficient (HRD) tumors including BRCA mutation. However, overlapping hematologic toxicity causes PARPi to fail in combination with some first-line chemotherapies. Furthermore, recent literature has demonstrated that PARP1 inhibition and PARP1-DNA trapping are key for antitumor activity in HRD cancer models. Currently approved PARPi have shown varying levels of selectivity for the entire 17-member PARP family, hence contribute to toxicity. Together, these findings above have provided the necessity and feasibility of developing next-generation PARPi with improved selectivity for PARP1, expanding significant clinical values and wide application prospects both in monotherapy and combination with other anticancer agents. In this review, we summery the latest research of current approved PARPi, discuss the current status and future promise of next-generation PARP1-selective inhibitor AZD5305, including its reported progress up to now and anticipated impact on clinical. |
| first_indexed | 2024-04-10T20:55:50Z |
| format | Article |
| id | doaj.art-9e3a18a1f1eb4cf1843556ebcaca1351 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-10T20:55:50Z |
| publishDate | 2023-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-9e3a18a1f1eb4cf1843556ebcaca13512023-01-23T04:59:07ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122023-01-011310.3389/fphar.2022.979873979873Current status and future promise of next-generation poly (ADP-Ribose) polymerase 1-selective inhibitor AZD5305Jingcao Zheng0Jingcao Zheng1Zhengyu Li2Zhengyu Li3Wenjiao Min4Department of Gynecology and Obstetrics, West China Second University Hospital, Sichuan University, Chengdu, ChinaKey Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, ChinaDepartment of Gynecology and Obstetrics, West China Second University Hospital, Sichuan University, Chengdu, ChinaKey Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, ChinaPsychosomatic Department, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu, ChinaThe family of poly (ADP-ribose) polymerases (PARPs) consists of 17 members, which have been demonstrated as having effects on a series of cellular processes, including DNA replication and repair. PARP inhibitors (PARPi) suppress DNA repair through “PARP trapping”, thus, constitute an important treatment option for cancer nowadays. In addition, PARP inhibition and homologous recombination repair (HRR) defects are synthetically lethal, giving a promising therapeutic for homologous recombination repair deficient (HRD) tumors including BRCA mutation. However, overlapping hematologic toxicity causes PARPi to fail in combination with some first-line chemotherapies. Furthermore, recent literature has demonstrated that PARP1 inhibition and PARP1-DNA trapping are key for antitumor activity in HRD cancer models. Currently approved PARPi have shown varying levels of selectivity for the entire 17-member PARP family, hence contribute to toxicity. Together, these findings above have provided the necessity and feasibility of developing next-generation PARPi with improved selectivity for PARP1, expanding significant clinical values and wide application prospects both in monotherapy and combination with other anticancer agents. In this review, we summery the latest research of current approved PARPi, discuss the current status and future promise of next-generation PARP1-selective inhibitor AZD5305, including its reported progress up to now and anticipated impact on clinical.https://www.frontiersin.org/articles/10.3389/fphar.2022.979873/fullPARP inhibitorsimproved selectivitynovel therapyoncologyAZD5305 |
| spellingShingle | Jingcao Zheng Jingcao Zheng Zhengyu Li Zhengyu Li Wenjiao Min Current status and future promise of next-generation poly (ADP-Ribose) polymerase 1-selective inhibitor AZD5305 Frontiers in Pharmacology PARP inhibitors improved selectivity novel therapy oncology AZD5305 |
| title | Current status and future promise of next-generation poly (ADP-Ribose) polymerase 1-selective inhibitor AZD5305 |
| title_full | Current status and future promise of next-generation poly (ADP-Ribose) polymerase 1-selective inhibitor AZD5305 |
| title_fullStr | Current status and future promise of next-generation poly (ADP-Ribose) polymerase 1-selective inhibitor AZD5305 |
| title_full_unstemmed | Current status and future promise of next-generation poly (ADP-Ribose) polymerase 1-selective inhibitor AZD5305 |
| title_short | Current status and future promise of next-generation poly (ADP-Ribose) polymerase 1-selective inhibitor AZD5305 |
| title_sort | current status and future promise of next generation poly adp ribose polymerase 1 selective inhibitor azd5305 |
| topic | PARP inhibitors improved selectivity novel therapy oncology AZD5305 |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.979873/full |
| work_keys_str_mv | AT jingcaozheng currentstatusandfuturepromiseofnextgenerationpolyadpribosepolymerase1selectiveinhibitorazd5305 AT jingcaozheng currentstatusandfuturepromiseofnextgenerationpolyadpribosepolymerase1selectiveinhibitorazd5305 AT zhengyuli currentstatusandfuturepromiseofnextgenerationpolyadpribosepolymerase1selectiveinhibitorazd5305 AT zhengyuli currentstatusandfuturepromiseofnextgenerationpolyadpribosepolymerase1selectiveinhibitorazd5305 AT wenjiaomin currentstatusandfuturepromiseofnextgenerationpolyadpribosepolymerase1selectiveinhibitorazd5305 |