S1PR1 modulators in multiple sclerosis: Efficacy, safety, comparison, and chemical structure insights

  • Eur J Med Chem. 2023 Mar 15:250:115182. doi: 10.1016/j.ejmech.2023.115182.
Omid Jamshidi Kandjani  1 ,  Shadi Yaqoubi  2 ,  Samad Shams Vahdati  3 ,  Behnam Borhannejad  4 ,  Siavoush Dastmalchi  5 ,  Ali Akbar Alizadeh  6
Affiliations
  • 1. Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Parmaceutical Analysis Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
  • 2. Research Center for Integrative Medicine in Aging, Aging Research Institute, Tabriz University of Medical Sciences, Tabriz, Iran.
  • 3. Emergency and Trauma Care Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
  • 4. Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran; School of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
  • 5. Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; School of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran; Faculty of Pharmacy, Near East University, POBOX:99138, Nicosia, North Cyprus, Mersin 10, Turkey.
  • 6. Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address: [email protected].
PMID: 36758307 DOI: 10.1016/j.ejmech.2023.115182
Abstract

Multiple sclerosis (MS) is a Neurological Disease that leads to severe physical and cognitive disabilities. Drugs used in the treatment of MS vary from small synthetic molecules to large macromolecules such as antibodies. Sphingosine 1-phosphate receptor modulators are frequently used for the treatment of MS. These medicines prevent the egress of lymphocytes from secondary lymphoid organs leading to immune system suppression. Currently, four S1PR modulators are on the market and several potential drug candidates are in clinical trials for the treatment of MS. These compounds differ in chemical structure, adverse effects, and efficacy points of view. The current article reviews the latest studies on S1PR1 modulators and compares them with Other MS drugs in terms of efficacy, tolerability, and safety. A special focus was dedicated to discussing the structure-activity relationships of these compounds and performing a three-dimensional quantitative structure-activity relationship (3D-QSAR) analysis to gain better insight into the ligand-receptor interaction mode.

Keywords
Bradycardia; Functional antagonists; Lymphopenia; Structure-activity relationship; Three dimensional structural features.
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