Nirav Dhanesha: Targeting FXI for Safer Anticoagulation
Nirav Dhanesha, Assistant Professor at the Louisiana State University, shared on LinkedIn about a recent article he and his colleagues co-authored, published in Blood Advances, adding:
”Happy to share our latest collaborative publication with Umesh Desai from Virginia Commonwealth University and his team in American Society of Hematology journal Blood Advances
Here, we presents a structurally and functionally unique, allosteric small molecule as a highly promising candidate for safer anticoagulation including Cancer-associated Thrombosis CAT
A few key takeaways from this work:
- Bridging Chemistry and Pharmacology: This project highlights how powerful close collaboration between chemists and pharmacologists can be. Working together allowed us to translate novel chemical design into robust biological validation.
- Challenging Medicinal Chemistry Dogma: Medicinal chemists often emphasize that drug-like molecules must be small and hydrophobic. Our findings demonstrate that non-saccharide synthetic mimetics of glycosaminoglycans NSGMs can deliver excellent potency, selectivity, and a strong safety window, offering a compelling alternative design strategy.
- Direct Clinical Relevance in Cancer-Associated Thrombosis CAT: We tested these novel molecules across multiple pre-clinical models, including a dedicated model of cancer-associated thrombosis CAT. Given the ongoing excitements (and some failures) exploring FXIa inhibitors for CAT in humans, these insights carry significant translational potential for patients who need safer anticoagulation options.
A big thank you to Umesh Desai at Virginia Commonwealth University and all co-authors for such a fruitful partnership with us at LSU Health Shreveport.
I learned a great deal about NSGMs and their therapeutic potential throughout this project!”
Title: A Synthetic, Small Molecule, Allosteric Inhibitor of Human Factor XIa for Thrombosis
Authors: Chiranjeev Sharma, Rama Gunta, Sridhar R Iyer, Rawan M Fayyad, Elsamani Abdelfadiel, Andrew K Hadsdy, Erika Martin, Priyanka Mishra, Bharath Kumar Villuri, Nilesh Pandey, Daniel K Afosah, Nehru Viji Sankaranarayanan, Bhaumik B Patel, Masahiro Sakagami, Nirav Dhanesha, Umesh R Desai
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