Abstract
Background: According to DCEG investigation, the compared results of the osteosarcoma incidences in different continents, reported it to be the most diagnosed in adolescents and adults above 60 yrs. old. Less than 15% of patients get cured with surgery alone but the addition of chemotherapy to the treatment increases the survival rate of patient by 58%-76%. Surgical resection and aggressive chemotherapy protocols are effective to an extent but have failed to improve the 5-year overall survival rate. Indubitably, new drugs and new therapeutic targets are required to improve the outcome as well as to diminish the long-term toxicities associated with the current benchmark of treatment. STAT3 appears to be an important mediator of chemoresistance in osteosarcoma.
Results: Experimental evidence clearly demonstrate the disruption of STAT3 signaling which inhibits the survival and proliferation of osteosarcoma and decreases the growth of disease. This prevailing study approach is by molecular docking, virtual screening to elucidate inhibitor with superior affinity against STAT3 to have a cautious pharma profile. To rectify the best-established drug with high affinity, Mol dock algorithm is executed. The compound Sorafenib (Pub CID 216239) having high-affinity scores is subjected to another similarity search to retrieve the drugs with similar properties. The virtual screened compound with PubChem CID-44815014 as per BOILED-Egg plot reveals its high affinity.
Conclusion: Comparative study and ADMET study both showed the compounds to have equivalent properties, whereas interestingly the virtual screened compound having PubChem CID-44815014 is seen to have the lowest rerank score. These drugs are identified to have high potential to act as STAT3 inhibitors and probably can be considered for further studies in wet lab analysis.
Keywords: STAT3, Osteosarcoma, Molecular docking, Virtual screening, ADMET, Cancer.
Current Topics in Medicinal Chemistry
Title:Structure-based Virtual Screening for the Identification of High-affinity Small Molecule Towards STAT3 for the Clinical Treatment of Osteosarcoma
Volume: 18 Issue: 29
Author(s): Ravina Khandelwal, Aashish Pratap Singh Chauhan, Swarnima Bilawat, Aishwarya Gandhe, Tajamul Hussain, Elizabeth Anne Hood, Anuraj Nayarisseri*Sanjeev Kumar Singh*
Affiliation:
- In silico Research Laboratory, Eminent Biosciences, Mahalakshmi Nagar, Indore – 452010, Madhya Pradesh,India
- Computer Aided Drug Designing and Molecular Modeling Lab, Department of Bioinformatics, Alagappa University, Karaikudi-630 003, Tamil Nadu,India
Keywords: STAT3, Osteosarcoma, Molecular docking, Virtual screening, ADMET, Cancer.
Abstract: Background: According to DCEG investigation, the compared results of the osteosarcoma incidences in different continents, reported it to be the most diagnosed in adolescents and adults above 60 yrs. old. Less than 15% of patients get cured with surgery alone but the addition of chemotherapy to the treatment increases the survival rate of patient by 58%-76%. Surgical resection and aggressive chemotherapy protocols are effective to an extent but have failed to improve the 5-year overall survival rate. Indubitably, new drugs and new therapeutic targets are required to improve the outcome as well as to diminish the long-term toxicities associated with the current benchmark of treatment. STAT3 appears to be an important mediator of chemoresistance in osteosarcoma.
Results: Experimental evidence clearly demonstrate the disruption of STAT3 signaling which inhibits the survival and proliferation of osteosarcoma and decreases the growth of disease. This prevailing study approach is by molecular docking, virtual screening to elucidate inhibitor with superior affinity against STAT3 to have a cautious pharma profile. To rectify the best-established drug with high affinity, Mol dock algorithm is executed. The compound Sorafenib (Pub CID 216239) having high-affinity scores is subjected to another similarity search to retrieve the drugs with similar properties. The virtual screened compound with PubChem CID-44815014 as per BOILED-Egg plot reveals its high affinity.
Conclusion: Comparative study and ADMET study both showed the compounds to have equivalent properties, whereas interestingly the virtual screened compound having PubChem CID-44815014 is seen to have the lowest rerank score. These drugs are identified to have high potential to act as STAT3 inhibitors and probably can be considered for further studies in wet lab analysis.
Export Options
About this article
Cite this article as:
Khandelwal Ravina , Chauhan Pratap Singh Aashish , Bilawat Swarnima , Gandhe Aishwarya , Hussain Tajamul , Hood Anne Elizabeth , Nayarisseri Anuraj*, Singh Kumar Sanjeev *, Structure-based Virtual Screening for the Identification of High-affinity Small Molecule Towards STAT3 for the Clinical Treatment of Osteosarcoma, Current Topics in Medicinal Chemistry 2018; 18 (29) . https://dx.doi.org/10.2174/1568026618666181115092001
DOI https://dx.doi.org/10.2174/1568026618666181115092001 |
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
-
Genetics of the First Seven Proprotein Convertase Enzymes in Health and Disease
Current Genomics Genetics and Molecular Biology of Tuberous Sclerosis Complex
Current Genomics Sleep in Pediatric Pulmonary Diseases
Current Respiratory Medicine Reviews Hybrid PET Imaging in Neurologic Disease: PET/MRI Rather than PET/CT
Current Medical Imaging Mast Cells in Lung Homeostasis: Beyond Type I Hypersensitivity
Current Respiratory Medicine Reviews Age Matching Animal Models to Humans - Theoretical Considerations
Current Drug Discovery Technologies Autoimmune Hepatitis
Current Pediatric Reviews An Update in the Management of Obesity: The Weight of CNS Targets
Recent Patents on CNS Drug Discovery (Discontinued) Foreword [The Largest Unmet Market: Chronic Diseases of Aging]
Mini-Reviews in Medicinal Chemistry Omega-3 Fatty Acids in the Management of Epilepsy
Current Topics in Medicinal Chemistry Lifelong and Prenatal Effects of Phytoestrogens
Current Bioactive Compounds Wnt / β-Catenin Signaling Pathway as Novel Cancer Drug Targets
Current Cancer Drug Targets Is Helicobacter pylori the Infectious Trigger for Headache?: A Review
Infectious Disorders - Drug Targets Hematological Malignancies and Pregnancy. A Brief Review
Reviews on Recent Clinical Trials Redox Processes in Neurodegenerative Disease Involving Reactive Oxygen Species
Current Neuropharmacology Management of Inflammatory Bowel Disease Patients with a Cancer History
Current Drug Targets Methylglyoxal, A Metabolite Increased in Diabetes is Associated with Insulin Resistance, Vascular Dysfunction and Neuropathies
Current Drug Metabolism Molecular Basis of Inflammation and Insulin Resistance in Obesity
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Cell Hierarchy, Metabolic Flexibility and Systems Approaches to Cancer Treatment
Current Pharmaceutical Biotechnology Repurposing of Metformin for Cancer Therapy: Updated Patent and Literature Review
Recent Patents on Anti-Cancer Drug Discovery