Identification of Repurposed FDA Drugs by Targeting Sclerostin via the Wnt Pathway for Alveolar Bone Formation

Pradeep K. Yadalam; Raghavendra V. Anegundi; Ramya Ramadoss; Deepti Shrivastava; Awsaf Murdhi Alruwaili; Muhammad Faheemuddin; Kumar Chandan Srivastava

doi:10.1055/s-0043-1777841

European Journal of General Dentistry, Inhaltsverzeichnis

CC BY 4.0 · European Journal of General Dentistry 2024; 13(02): 125-133
DOI: 10.1055/s-0043-1777841

Original Article

Identification of Repurposed FDA Drugs by Targeting Sclerostin via the Wnt Pathway for Alveolar Bone Formation

Pradeep K. Yadalam

¹Department of Periodontics, Saveetha Dental College, Saveetha Institute of Medical and Technical Sciences , Saveetha University, Chennai, Tamil Nadu, India

,

Raghavendra V. Anegundi

¹Department of Periodontics, Saveetha Dental College, Saveetha Institute of Medical and Technical Sciences , Saveetha University, Chennai, Tamil Nadu, India

,

Ramya Ramadoss

²Department of Oral Pathology and Oral Biology, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India

,

Deepti Shrivastava

³Periodontics Division, Preventive Dentistry Department, College of Dentistry, Jouf University, Sakaka, Saudi Arabia

,

Awsaf Murdhi Alruwaili

⁴College of Dentistry, Jouf University, Sakaka, Saudi Arabia

,

Muhammad Faheemuddin

⁵Department of Prosthodontics and Implantology, College of Dentistry, King Faisal University, Al-Ahsa, Saudi Arabia

,

Kumar Chandan Srivastava

⁶Oral Medicine and Maxillofacial Radiology Division, Department of Oral and Maxillofacial Surgery and Diagnostic Sciences, College of Dentistry, Jouf University, Sakaka, Saudi Arabia

⁷Department of Oral Medicine and Radiology, Saveetha Dental College, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, Tamil Nadu, India

› Institutsangaben

Abstract

Objective Natural wingless-related integration site (Wnt) pathway antagonist sclerostin (SOST) has attracted much attention because unusual bone illnesses characterized by the increased bone mass result from its absence of action. The Wnt ligand is prevented from attaching to the Frizzled family receptor when SOST is present. In the active destruction complex, -catenin is phosphorylated. -Catenin molecules do not enter the nucleus and are broken down by a proteasome. As a result, Wnt-responsive genes are not activated, which lowers bone formation and raises bone resorption. A humanized monoclonal antibody called romosozumab binds to and inhibits SOST with significant cardiac side effects. As a result, the current study's objective is to find and screen Food and Drug Administration (FDA) medications that target SOST.

Materials and Methods SOST's structure was retrieved from Protein Data Bank (PDB) (ID: 6l6r). Pharmacophore modeling and molecular operating environment-based virtual testing of FDA-approved medicines. Using the Desmond program, docking and molecular dynamics simulations were performed.

Results Our findings revealed medications with FDA approval (ZINC000253387843) Amphotericin B. The stability and receptor–ligand interactions are pretty substantial, as demonstrated by the findings of docking and Molecular dynamics simulations, which have a docking score of −7.3 k/mol and root mean square deviation stability at 40 nanoseconds, respectively.

Conclusion The suggested pharmacological therapy shows promise since it uses the Wnt pathway to target the primary bone formation mechanism. However, additional prospective studies are required to apply the available data to clinical practice.

Keywords

bone remodeling - sclerostin - periodontal disease - Wnt pathway - osteoblast

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Referenzen

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