We have located links that may give you full text access.
Discovery of the small molecular inhibitors against sclerostin loop3 as potential anti-osteoporosis agents by structural based virtual screening and molecular design.
European Journal of Medicinal Chemistry 2024 April 17
Sclerostin is a secreted glycoprotein that expresses predominantly in osteocytes and inhibits bone formation by antagonizing the Wnt/β-catenin signaling pathway, and the loop3 region of sclerostin has recently discovered as a novel therapeutic target for bone anabolic treatment without increasing cardiovascular risk. Herein, we used a structural based virtual screening to search for small molecular inhibitors selectively targeting sclerostin loop3. A novel natural product hit ZINC4228235 (THFA) was identified as the sclerostin loop3-selective inhibitor with a Kd value of 42.43 nM against sclerostin loop3. The simplification and derivation of THFA using molecular modeling-guided modification allowed the discovery of an effective and loop3-selective small molecular inhibitor, compound (4-(3-acetamidoprop-1-yn-1-yl)benzoyl)glycine (AACA), with improved binding affinity (Kd = 15.4 nM) compared to the hit THFA. Further in-vitro experiment revealed that compound AACA could attenuate the suppressive effect of transfected sclerostin on Wnt signaling and bone formation. These results make AACA as a potential candidate for development of anti-osteoporosis agents without increasing cardiovascular risk.
Full text links
Related Resources
Trending Papers
Advances in Clinical Cardiology 2023: A Summary of Key Clinical Trials.Advances in Therapy 2024 May 15
Nutrition in the intensive care unit: from the acute phase to beyond.Intensive Care Medicine 2024 May 22
The Therapy and Management of Heart Failure with Preserved Ejection Fraction: New Insights on Treatment.Cardiac Failure Review 2024
Sodium-glucose co-transporter protein 2 (SGLT2) inhibitors for people with chronic kidney disease and diabetes.Cochrane Database of Systematic Reviews 2024 May 22
Bronchiectasis management in adults: state of the art and future directions.European Respiratory Journal 2024 May 24
Drug Therapy for Acute and Chronic Heart Failure with Preserved Ejection Fraction with Hypertension: A State-of-the-Art Review.American Journal of Cardiovascular Drugs : Drugs, Devices, and Other Interventions 2024 April 5
Pathophysiological Link and Treatment Implication of Heart Failure and Preserved Ejection Fraction in Patients with Chronic Kidney Disease.Biomedicines 2024 April 31
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app