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Repurposing raltegravir for reducing inflammation and treating cancer: a bioinformatics analysis
Zahra Nikfarjam1, Reza Rakhshi2, Farshid Zargari3,4
1Department of Physical & Computational Chemistry, Chemistry and Chemical Engineering Research Center of Iran, Tehran, Iran.
Scientific Reports
|December 5, 2024
Summary
This study repurposed the antiviral drug Raltegravir to inhibit ADAM17, a key enzyme in inflammation and cancer. Raltegravir shows promise in preventing severe inflammatory responses and tumorigenesis linked to ADAM17 malfunction.
Area of Science:
- Biochemistry
- Pharmacology
- Computational Biology
Background:
- Inflammation is a critical defense mechanism, but its dysregulation, particularly involving ADAM17 (a zinc-dependent metalloprotease), can drive disease.
- ADAM17 plays a crucial role in activating inflammatory and growth factors, and its malfunction is linked to increased growth, inflammation, and tissue damage.
Purpose of the Study:
- To identify and repurpose existing drugs for suppressing ADAM17 activity.
- To investigate potential therapeutic strategies for conditions associated with ADAM17 dysregulation, including inflammation and tumorigenesis.
Main Methods:
- Utilized bioinformatics approaches, including molecular docking, molecular dynamics simulations, and pharmacokinetic studies.
- Screened FDA-approved drugs for their ability to inhibit ADAM17, assessing interactions with active site amino acids and pharmacokinetic profiles.
Main Results:
- Identified five FDA-approved drugs (Raltegravir, Conivaptan, Paclitaxel, Saquinavir, Venetoclax) capable of inhibiting ADAM17 activity without strong zinc-binding groups.
- In silico analysis highlighted Raltegravir for its favorable interaction with ADAM17's active site and superior pharmacokinetic properties compared to the other identified drugs.
Conclusions:
- Raltegravir, an antiviral medication, is a potential candidate for drug repurposing to mitigate severe inflammatory responses and tumorigenesis driven by ADAM17 malfunction.
- The findings support the use of bioinformatics tools in identifying novel therapeutic applications for existing drugs targeting metalloproteases like ADAM17.
