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Updated: Feb 2, 2026
Large Scale Zebrafish-Based In vivo Small Molecule Screen
Published on: December 30, 2010
Structure-based Virtual Screening for the Identification of High-affinity Small Molecule Towards STAT3 for the
Ravina Khandelwal1, Aashish Pratap Singh Chauhan1, Swarnima Bilawat1
1In silico Research Laboratory, Eminent Biosciences, Mahalakshmi Nagar, Indore - 452010, Madhya Pradesh, India.
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.
Insights
New therapeutic targets are needed for osteosarcoma treatment. This study identifies potential STAT3 inhibitors, including a novel compound, to improve patient outcomes and reduce treatment toxicity.
Area of Science:
- Oncology
- Pharmacology
- Computational Chemistry
Background:
- Osteosarcoma is a prevalent cancer in adolescents and older adults.
- Current treatments including surgery and chemotherapy have limited efficacy, with a 5-year survival rate below 76%.
- Signal transducer and activator of transcription 3 (STAT3) is implicated in chemoresistance in osteosarcoma.
Purpose of the Study:
- To identify novel STAT3 inhibitors for osteosarcoma treatment.
- To discover new therapeutic targets to overcome chemoresistance and reduce treatment toxicity.
Main Methods:
- Virtual screening and molecular docking were employed to identify compounds with high affinity for STAT3.
- The Mol dock algorithm was used to evaluate drug affinity.
- A similarity search was performed on identified compounds.
- ADMET (Absorption, Distribution, Metabolism, Excretion, Toxicity) properties were assessed using the BOILED-Egg model.
Main Results:
- Experimental evidence indicates that disrupting STAT3 signaling inhibits osteosarcoma survival and proliferation.
- Sorafenib (Pub CID 216239) exhibited high affinity for STAT3.
- A virtual screened compound (PubChem CID-44815014) demonstrated high affinity and favorable ADMET properties.
- The compound with PubChem CID-44815014 showed the lowest rerank score in comparative and ADMET studies.
Conclusions:
- The identified compounds, particularly the one with PubChem CID-44815014, show significant potential as STAT3 inhibitors.
- These compounds warrant further investigation in wet lab studies for osteosarcoma treatment.
- Targeting STAT3 offers a promising strategy to improve osteosarcoma patient outcomes and mitigate treatment-related toxicities.
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