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An Update on Poly(ADP-ribose)polymerase-1 (PARP-1) Inhibitors: Opportunities and Challenges in Cancer Therapy.
J Med Chem. 2016 11 10; 59(21):9575-9598.JM

Abstract

Poly(ADP-ribose)polymerase-1 (PARP-1) is a critical DNA repair enzyme in the base excision repair pathway. Inhibitors of this enzyme comprise a new type of anticancer drug that selectively kills cancer cells by targeting homologous recombination repair defects. Since 2010, important advances have been achieved in PARP-1 inhibitors. Specifically, the approval of olaparib in 2014 for the treatment of ovarian cancer with BRCA mutations validated PARP-1 as an anticancer target and established its clinical importance in cancer therapy. Here, we provide an update on PARP-1 inhibitors, focusing on breakthroughs in their clinical applications and investigations into relevant mechanisms of action, biomarkers, and drug resistance. We also provide an update on the design strategies and the structural types of PARP-1 inhibitors. Opportunities and challenges in PARP-1 inhibitors for cancer therapy will be discussed based on the above advances.

Authors+Show Affiliations

Wang YQ
Division of Antitumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , Shanghai 201203, China.
Wang PY
CAS Key Laboratory of Receptor Research, and Synthetic Organic & Medicinal Chemistry Laboratory, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , 555 Zuchongzhi Lu, Building 3, Room 426, Pudong, Shanghai 201203, China. Key Laboratory of Pesticide & Chemical Biology, Ministry of Education, College of Chemistry, Central China Normal University , Wuhan 430079, China.
Wang YT
Division of Antitumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , Shanghai 201203, China.
Yang GF
Key Laboratory of Pesticide & Chemical Biology, Ministry of Education, College of Chemistry, Central China Normal University , Wuhan 430079, China.
Zhang A
CAS Key Laboratory of Receptor Research, and Synthetic Organic & Medicinal Chemistry Laboratory, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , 555 Zuchongzhi Lu, Building 3, Room 426, Pudong, Shanghai 201203, China.
Miao ZH
Division of Antitumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , Shanghai 201203, China.

MeSH

Antineoplastic AgentsCell ProliferationDose-Response Relationship, DrugDrug Screening Assays, AntitumorHumansModels, MolecularMolecular StructureNeoplasmsPoly (ADP-Ribose) Polymerase-1Poly(ADP-ribose) Polymerase InhibitorsStructure-Activity Relationship

Pub Type(s)

Journal Article
Review
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

27416328

Citation

Wang, Ying-Qing, et al. "An Update On Poly(ADP-ribose)polymerase-1 (PARP-1) Inhibitors: Opportunities and Challenges in Cancer Therapy." Journal of Medicinal Chemistry, vol. 59, no. 21, 2016, pp. 9575-9598.
Wang YQ, Wang PY, Wang YT, et al. An Update on Poly(ADP-ribose)polymerase-1 (PARP-1) Inhibitors: Opportunities and Challenges in Cancer Therapy. J Med Chem. 2016;59(21):9575-9598.
Wang, Y. Q., Wang, P. Y., Wang, Y. T., Yang, G. F., Zhang, A., & Miao, Z. H. (2016). An Update on Poly(ADP-ribose)polymerase-1 (PARP-1) Inhibitors: Opportunities and Challenges in Cancer Therapy. Journal of Medicinal Chemistry, 59(21), 9575-9598.
Wang YQ, et al. An Update On Poly(ADP-ribose)polymerase-1 (PARP-1) Inhibitors: Opportunities and Challenges in Cancer Therapy. J Med Chem. 2016 11 10;59(21):9575-9598. PubMed PMID: 27416328.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - An Update on Poly(ADP-ribose)polymerase-1 (PARP-1) Inhibitors: Opportunities and Challenges in Cancer Therapy. AU - Wang,Ying-Qing, AU - Wang,Ping-Yuan, AU - Wang,Yu-Ting, AU - Yang,Guang-Fu, AU - Zhang,Ao, AU - Miao,Ze-Hong, Y1 - 2016/07/27/ PY - 2016/7/15/pubmed PY - 2017/6/9/medline PY - 2016/7/15/entrez SP - 9575 EP - 9598 JF - Journal of medicinal chemistry JO - J Med Chem VL - 59 IS - 21 N2 - Poly(ADP-ribose)polymerase-1 (PARP-1) is a critical DNA repair enzyme in the base excision repair pathway. Inhibitors of this enzyme comprise a new type of anticancer drug that selectively kills cancer cells by targeting homologous recombination repair defects. Since 2010, important advances have been achieved in PARP-1 inhibitors. Specifically, the approval of olaparib in 2014 for the treatment of ovarian cancer with BRCA mutations validated PARP-1 as an anticancer target and established its clinical importance in cancer therapy. Here, we provide an update on PARP-1 inhibitors, focusing on breakthroughs in their clinical applications and investigations into relevant mechanisms of action, biomarkers, and drug resistance. We also provide an update on the design strategies and the structural types of PARP-1 inhibitors. Opportunities and challenges in PARP-1 inhibitors for cancer therapy will be discussed based on the above advances. SN - 1520-4804 UR - https://www.unboundmedicine.com/medline/citation/27416328/An_Update_on_Poly_ADP_ribose_polymerase_1__PARP_1__Inhibitors:_Opportunities_and_Challenges_in_Cancer_Therapy_ DB - PRIME DP - Unbound Medicine ER -