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Structure-based virtual screening for the identification of high affinity small molecule towards STAT3 for the clinical treatment of Osteosarcoma

Author(s):

Ravina Khandelwal, Aashish Pratap Singh Chauhan, Tajamul Hussain, Elizabeth Anne Hood* and Anuraj Nayarisseri  

Abstract:


According to DCEG investigation, the compared results of the osteosarcoma incidences in different continents, reported it to be mostly diagnosed in adolescents and adults above 60 yrs. old. Less than 15% number of patients get cured with surgery alone but 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 chemo resistance in osteosarcoma. Experimental evidences 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. 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

Affiliation:

In silico Research Laboratory, Eminent Biosciences, Mahalakshmi Nagar, Indore – 452010, Madhya Pradesh, In silico Research Laboratory, Eminent Biosciences, Mahalakshmi Nagar, Indore – 452010, Madhya Pradesh, Center of Excellence in Biotechnology Research, College of Science, King Saud University, Riyadh, Chemistry and Biochemistry Department, University of Missouri, St. Louis, MO, In silico Research Laboratory, Eminent Biosciences, Mahalakshmi Nagar, Indore – 452010, Madhya Pradesh



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