{"title":"PARP-1抑制剂综述:评估新出现的前景和量身定制的治疗策略。","authors":"Soundarya Ramesh, Shannon D Almeida, Sameerana Hammigi, Govardan Katta Radhakrishna, Golla Sireesha, Theivendren Panneerselvam, Shangavi Vellingiri, Selvaraj Kunjiappan, Damodar Nayak Ammunje, Parasuraman Pavadai","doi":"10.1055/a-2181-0813","DOIUrl":null,"url":null,"abstract":"<p><p>Eukaryotic organisms contain an enzyme family called poly (ADP-ribose) polymerases (PARPs), which is responsible for the poly (ADP-ribosylation) of DNA-binding proteins. PARPs are members of the cell signaling enzyme class. PARP-1, the most common isoform of the PARP family, is responsible for more than 90% of the tasks carried out by the PARP family as a whole. A superfamily consisting of 18 PARPs has been found. In order to synthesize polymers of ADP-ribose (PAR) and nicotinamide, the DNA damage nick monitor PARP-1 requires NAD+ as a substrate. The capability of PARP-1 activation to boost the transcription of proinflammatory genes, its ability to deplete cellular energy pools, which leads to cell malfunction and necrosis, and its involvement as a component in the process of DNA repair are the three consequences of PARP-1 activation that are of particular significance in the process of developing new drugs. As a result, the pharmacological reduction of PARP-1 may result in an increase in the cytotoxicity toward cancer cells.</p>","PeriodicalId":11451,"journal":{"name":"Drug Research","volume":null,"pages":null},"PeriodicalIF":1.7000,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"A Review of PARP-1 Inhibitors: Assessing Emerging Prospects and Tailoring Therapeutic Strategies.\",\"authors\":\"Soundarya Ramesh, Shannon D Almeida, Sameerana Hammigi, Govardan Katta Radhakrishna, Golla Sireesha, Theivendren Panneerselvam, Shangavi Vellingiri, Selvaraj Kunjiappan, Damodar Nayak Ammunje, Parasuraman Pavadai\",\"doi\":\"10.1055/a-2181-0813\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Eukaryotic organisms contain an enzyme family called poly (ADP-ribose) polymerases (PARPs), which is responsible for the poly (ADP-ribosylation) of DNA-binding proteins. PARPs are members of the cell signaling enzyme class. PARP-1, the most common isoform of the PARP family, is responsible for more than 90% of the tasks carried out by the PARP family as a whole. A superfamily consisting of 18 PARPs has been found. In order to synthesize polymers of ADP-ribose (PAR) and nicotinamide, the DNA damage nick monitor PARP-1 requires NAD+ as a substrate. The capability of PARP-1 activation to boost the transcription of proinflammatory genes, its ability to deplete cellular energy pools, which leads to cell malfunction and necrosis, and its involvement as a component in the process of DNA repair are the three consequences of PARP-1 activation that are of particular significance in the process of developing new drugs. As a result, the pharmacological reduction of PARP-1 may result in an increase in the cytotoxicity toward cancer cells.</p>\",\"PeriodicalId\":11451,\"journal\":{\"name\":\"Drug Research\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.7000,\"publicationDate\":\"2023-11-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Drug Research\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1055/a-2181-0813\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2023/10/27 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Drug Research","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1055/a-2181-0813","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/10/27 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
A Review of PARP-1 Inhibitors: Assessing Emerging Prospects and Tailoring Therapeutic Strategies.
Eukaryotic organisms contain an enzyme family called poly (ADP-ribose) polymerases (PARPs), which is responsible for the poly (ADP-ribosylation) of DNA-binding proteins. PARPs are members of the cell signaling enzyme class. PARP-1, the most common isoform of the PARP family, is responsible for more than 90% of the tasks carried out by the PARP family as a whole. A superfamily consisting of 18 PARPs has been found. In order to synthesize polymers of ADP-ribose (PAR) and nicotinamide, the DNA damage nick monitor PARP-1 requires NAD+ as a substrate. The capability of PARP-1 activation to boost the transcription of proinflammatory genes, its ability to deplete cellular energy pools, which leads to cell malfunction and necrosis, and its involvement as a component in the process of DNA repair are the three consequences of PARP-1 activation that are of particular significance in the process of developing new drugs. As a result, the pharmacological reduction of PARP-1 may result in an increase in the cytotoxicity toward cancer cells.
期刊介绍:
Drug Research (formerly Arzneimittelforschung) is an international peer-reviewed journal with expedited processing times presenting the very latest research results related to novel and established drug molecules and the evaluation of new drug development. A key focus of the publication is translational medicine and the application of biological discoveries in the development of drugs for use in the clinical environment. Articles and experimental data from across the field of drug research address not only the issue of drug discovery, but also the mathematical and statistical methods for evaluating results from industrial investigations and clinical trials. Publishing twelve times a year, Drug Research includes original research articles as well as reviews, commentaries and short communications in the following areas: analytics applied to clinical trials chemistry and biochemistry clinical and experimental pharmacology drug interactions efficacy testing pharmacodynamics pharmacokinetics teratology toxicology.