Logo Medical Science Monitor

Call: +1.631.470.9640
Mon - Fri 10:00 am - 02:00 pm EST

Contact Us

Logo Medical Science Monitor Logo Medical Science Monitor Logo Medical Science Monitor

02 May 2003

Pharmacological inhibition of poly(ADP-ribose) polymerase (PARP)

G. Southan, C. Szabo

Med Sci Monit 2003; 9(1): 63- :: ID: 15202

Abstract

Poly(ADP-ribose) polymerase-1 (PARP-1) is the principal member of the PARP enzyme family consisting of PARP-1 and several recently identified novel poly(ADP-ribosyl)ating enzymes. PARP-1 functions as a DNA nick sensor enzyme. Upon binding to DNA breaks, activated PARP cleaves NAD+ into nicotinamide and ADP-ribose and polymerizes the latter onto nuclear acceptor proteins including histones, transcription factors and PARP itself. Poly(ADP-ribosyl)ation contributes to inflammatory signal transduction processes. In addition, oxidative stress-induced overactivation of PARP consumes NAD+ and consequently ATP, culminating in cell dysfunction or necrosis. PARP activation has been implicated in the pathogenesis of stroke, myocardial ischemia, diabetes, diabetes-associated cardiovascular dysfunction, shock, traumatic central nervous system injury, arthritis, colitis, allergic encephalomyelitis and various other forms of inflammation. Therefore, inhibition of PARP by pharmacological agents may prove useful for the therapy of these diseases, as has been shown in preclinical animal models of these diseases. Moreover, PARP inhibitors may have additional, potential utility as anticancer agents, radiosensitizers and antiviral agents. Here we overview the structures and pharmacological actions of various pharmacological classes of compounds which inhibit the catalytic activity of PARP and will present novel biochemical and pharmacological data, as well as in vivo efficacy data with PJ34, a potent, phenanthridinone-based PARP inhibitor, as well as with EB47 and INO-1001, members of two novel series of ultrapotent PARP inhibitors. References: 1.Virág L, Szabó C: The therapeutic potential of PARP inhibition. Pharmacological Reviews, 2002; 54: 375-429 2.Jagtap P, Soriano FG, Virag L et al: Novel phenanthridinone inhibitors of poly(ADP-ribose) synthetase: potent cytoprotective and anti-shock agents. Crit Care Med, 2002; 30: 1071-82 3.Southan GJ, Szabó C: Inhibitors of poly(ADP-ribose) polymerase. Current Med Chem, in press, 2003

Keywords: pharmacological inhibitors, NAD, competitive inhibition, potency, efficacy

Comments

Editorial

01 May 2022 : Editorial  

Editorial: Cardiovascular Complications at One Year After SARS-CoV-2 Infection are Independent of Underlying Cardiovascular Risk Factors or Severity of COVID-19

Dinah V. Parums
Science Editor, Medical Science Monitor, International Scientific Information, Inc., Melville, NY, USA

DOI: 10.12659/MSM.937048

Med Sci Monit 2022; 28:e937048

SARS-CoV-2/COVID-19

24 May 2022 : Clinical Research  

Screening for SARS-CoV-2 Infection in Students at the Medical University of Warsaw, Poland Between November...

Med Sci Monit In Press; DOI: 10.12659/MSM.936962  

04 May 2022 : Clinical Research  

Effects of Wearing Face Masks on Exercise Capacity and Ventilatory Anaerobic Threshold in Healthy Subjects ...

Med Sci Monit In Press; DOI: 10.12659/MSM.936069  

27 May 2022 : Clinical Research  

Factors Associated with Falls During Hospitalization for Coronavirus Disease 2019 (COVID-19)

Med Sci Monit 2022; 28:e936547

In Press

27 May 2022 : Clinical Research  

Prognostic Significance of Preoperative Integrated Liver Inflammatory Score in Patients with Hepatocellular...

Med Sci Monit In Press; DOI: 10.12659/MSM.937005  

25 May 2022 : Review article  

Narrative Review of the Mechanism of Hip Prosthesis Dislocation and Methods to Reduce the Risk of Dislocation

Med Sci Monit In Press; DOI: 10.12659/MSM.935665  

24 May 2022 : Clinical Research  

Remimazolam Tosilate Sedation with Adjuvant Sufentanil in Chinese Patients with Liver Cirrhosis Undergoing ...

Med Sci Monit In Press; DOI: 10.12659/MSM.936580  

24 May 2022 : Clinical Research  

Screening for SARS-CoV-2 Infection in Students at the Medical University of Warsaw, Poland Between November...

Med Sci Monit In Press; DOI: 10.12659/MSM.936962  

Most Viewed Current Articles

30 Dec 2021 : Clinical Research  

Retrospective Study of Outcomes and Hospitalization Rates of Patients in Italy with a Confirmed Diagnosis o...

DOI :10.12659/MSM.935379

Med Sci Monit 2021; 27:e935379

08 Mar 2022 : Review article  

A Review of the Potential Roles of Antioxidant and Anti-Inflammatory Pharmacological Approaches for the Man...

DOI :10.12659/MSM.936292

Med Sci Monit 2022; 28:e936292

01 Nov 2020 : Review article  

Long-Term Respiratory and Neurological Sequelae of COVID-19

DOI :10.12659/MSM.928996

Med Sci Monit 2020; 26:e928996

01 Jan 2022 : Editorial  

Editorial: Current Status of Oral Antiviral Drug Treatments for SARS-CoV-2 Infection in Non-Hospitalized Pa...

DOI :10.12659/MSM.935952

Med Sci Monit 2022; 28:e935952

Your Privacy

We use cookies to ensure the functionality of our website, to personalize content and advertising, to provide social media features, and to analyze our traffic. If you allow us to do so, we also inform our social media, advertising and analysis partners about your use of our website, You can decise for yourself which categories you you want to deny or allow. Please note that based on your settings not all functionalities of the site are available. View our privacy policy.

Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750