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
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
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...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
-
Hepatocyte Growth Factor Signaling in Cancer Metastasis
Current Signal Transduction Therapy Endometrial Cancer as a Familial Tumor: Pathology and Molecular Carcinogenesis (Review)
Current Genomics Enhanced Expression of miR-199b-5p Promotes Proliferation of Pancreatic β-Cells by Down-Regulation of MLK3
MicroRNA Antitumor Therapeutic Strategies Based on the Targeting of Epidermal Growth Factor-Induced Survival Pathways
Current Drug Targets Helicase Domain Containing Proteins in Human Disorders
Current Genomics Critical microRNAs in Lung Cancer: Recent Advances and Potential Applications
Anti-Cancer Agents in Medicinal Chemistry Micro-/Nano-Scale Biointerfaces, Mechanical Coupling and Cancer Therapy
Current Topics in Medicinal Chemistry Roles of EGFR, PI3K, AKT, and mTOR in Heavy Metal-Induced Cancer
Current Cancer Drug Targets Human Exposure to Endocrine Disruptors and Breast Milk
Endocrine, Metabolic & Immune Disorders - Drug Targets Nonviral Vectors for Cancer Gene Therapy: Prospects for Integrating Vectors and Combination Therapies
Current Gene Therapy A Simple and Reliable Approach for Assessing Anticancer Activity In Vitro
Current Medicinal Chemistry Toxicity of Biodegradable Nanoscale Preparations
Current Drug Metabolism Mitochondrial VDAC1: Function in Cell Life and Death and a Target for Cancer Therapy
Current Medicinal Chemistry MicroRNAs and Pancreatic Cancer: Current Research and Future Outlooks
Current Signal Transduction Therapy Minocycline Inhibits mTOR Signaling Activation and Alleviates Behavioral Deficits in the Wistar Rats with Acute Ischemia stroke
CNS & Neurological Disorders - Drug Targets MicroRNAs as Regulators in Normal Hematopoietic and Leukemia Stem Cells: Current Concepts and Clinical Implications
Current Molecular Medicine Curcumin and its Formulations: Potential Anti-Cancer Agents
Anti-Cancer Agents in Medicinal Chemistry Potential Role of TRAIL in the Management of Autoimmune Diabetes Mellitus
Current Pharmaceutical Design Phosphoinositide-3 Kinase Signaling in Cardiac Hypertrophy and Heart Failure
Current Pharmaceutical Design Mitophagy in Carcinogenesis and Tumour Progression- A New Paradigm with Emerging Importance
Anti-Cancer Agents in Medicinal Chemistry