Abstract
A tremendous research on Poly (ADP-ribose) polymerase (PARP) pertaining to cancer and ischemia is in very rapid progress. PARP’s are a specific class of enzymes that repairs the damaged DNA. Recent findings suggest also that PARP-1 is the most abundantly expressed nuclear enzyme which involves in various therapeutic areas like inflammation, stroke, cardiac ischemia, cancer and diabetes. The current review describes the overview on clinical candidates of PARP1 and its current status in clinical trials. This paper also covers identification of potent PARP1 inhibitors using structure and ligand based pharmacophore models. Finally 36 potential hits were identified from the virtual screening of pharmacophore models and screened for PARP1 activity. 15 actives were identified as potent PARP1 inhibitors and further optimization of these analogues are in progress.
Keywords: Cancer, docking, glide, PARP1, pharmacophore, virtual screening.
Current Topics in Medicinal Chemistry
Title:A Review on PARP1 Inhibitors: Pharmacophore Modeling, Virtual and Biological Screening Studies to Identify Novel PARP1 Inhibitors
Volume: 14 Issue: 17
Author(s): Sardar Shamshair Singh, Jagarlapudi A.R.P. Sarma, Lakshmi Narasu, Raveendra Dayam, Shili Xu and Nouri Neamati
Affiliation:
Keywords: Cancer, docking, glide, PARP1, pharmacophore, virtual screening.
Abstract: A tremendous research on Poly (ADP-ribose) polymerase (PARP) pertaining to cancer and ischemia is in very rapid progress. PARP’s are a specific class of enzymes that repairs the damaged DNA. Recent findings suggest also that PARP-1 is the most abundantly expressed nuclear enzyme which involves in various therapeutic areas like inflammation, stroke, cardiac ischemia, cancer and diabetes. The current review describes the overview on clinical candidates of PARP1 and its current status in clinical trials. This paper also covers identification of potent PARP1 inhibitors using structure and ligand based pharmacophore models. Finally 36 potential hits were identified from the virtual screening of pharmacophore models and screened for PARP1 activity. 15 actives were identified as potent PARP1 inhibitors and further optimization of these analogues are in progress.
Export Options
About this article
Cite this article as:
Singh Shamshair Sardar, Sarma A.R.P. Jagarlapudi, Narasu Lakshmi, Dayam Raveendra, Xu Shili and Neamati Nouri, A Review on PARP1 Inhibitors: Pharmacophore Modeling, Virtual and Biological Screening Studies to Identify Novel PARP1 Inhibitors, Current Topics in Medicinal Chemistry 2014; 14 (17) . https://dx.doi.org/10.2174/1568026614666140929152123
DOI https://dx.doi.org/10.2174/1568026614666140929152123 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
AlphaFold in Medicinal Chemistry: Opportunities and Challenges
AlphaFold, a groundbreaking AI tool for protein structure prediction, is revolutionizing drug discovery. Its near-atomic accuracy unlocks new avenues for designing targeted drugs and performing efficient virtual screening. However, AlphaFold's static predictions lack the dynamic nature of proteins, crucial for understanding drug action. This is especially true for multi-domain proteins, ...read more
Artificial intelligence for Natural Products Discovery and Development
Our approach involves using computational methods to predict the potential therapeutic benefits of natural products by considering factors such as drug structure, targets, and interactions. We also employ multitarget analysis to understand the role of drug targets in disease pathways. We advocate for the use of artificial intelligence in predicting ...read more
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Targeted Therapies in the Treatment of Advanced Renal Cell Carcinoma
Recent Patents on Anti-Cancer Drug Discovery Low Dose Decitabine Combined with Taxol and Platinum Chemotherapy to Treat Refractory/Recurrent Ovarian Cancer: An Open-Label, Single-Arm, Phase I/II Study
Current Protein & Peptide Science Natural Compounds Containing a Condensed Cyclopropane Ring. Natural and Synthetic Aspects
Current Organic Chemistry A Natural Membrane Vesicle Exosome-based Sinomenine Delivery Platform for Hepatic Carcinoma Therapy
Current Topics in Medicinal Chemistry Compounds From Celastraceae Targeting Cancer Pathways and Their Potential Application in Head and Neck Squamous Cell Carcinoma: A Review
Current Genomics Semaphorins and their Receptors in Stem and Cancer Cells
Current Medicinal Chemistry Apoptosis Following Photodynamic Tumor Therapy: Induction, Mechanisms and Detection
Current Pharmaceutical Design Lipid Nanoparticles and their Application in Nanomedicine
Current Pharmaceutical Biotechnology The Role of Circulating Endothelial Progenitor Cells in Tumor Angiogenesis
Current Stem Cell Research & Therapy Anti-cancer Immunotoxins, Challenges, and Approaches
Current Pharmaceutical Design Progress of Stimuli-Responsive Nanoscale Metal Organic Frameworks as Controlled Drug Delivery Systems
Current Drug Delivery Personalized Peptide Vaccine for Treatment of Advanced Cancer
Current Medicinal Chemistry Endothelial Cell Targeted Molecular Imaging in Tumor Angiogenesis: Strategies and Current Status
Current Pharmaceutical Biotechnology Oligonucleotides as Anticancer Agents: From the Benchside to the Clinic and Beyond
Current Pharmaceutical Design The Ubiquitin-Proteasome System (UPS) and the Mechanism of Action of Bortezomib
Current Pharmaceutical Design The Pro-Survival Function of Akt Kinase can be Overridden or Altered to Contribute to Induction of Apoptosis
Current Cancer Drug Targets Chemosensitization and Immunosensitization of Resistant Cancer Cells to Apoptosis and Inhibition of Metastasis by the Specific NF-κB Inhibitor DHMEQ
Current Pharmaceutical Design Thioethers: An Overview
Current Drug Targets Intracellular Trafficking of MDR Transporters and Relevance of SNPs
Current Topics in Medicinal Chemistry Immunotherapy in Breast Cancer- Paving New Roads?
Current Molecular Pharmacology