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.
