2. Academic Validation
  3. A Mechanism-Based Sphingosine-1-phosphate Lyase Inhibitor

A Mechanism-Based Sphingosine-1-phosphate Lyase Inhibitor

  • J Org Chem. 2020 Jan 17;85(2):419-429. doi: 10.1021/acs.joc.9b02420.
Guillem Pons 1,  Daniel Riba 1,  Mireia Casasampere 1 2,  Eduardo Izquierdo 1 2,  José-Luís Abad 1,  Gemma Fabriàs 1 3,  Pilar G Rodríguez Ortega 4,  Juan J López-González 4,  Manuel Montejo 4,  Josefina Casas 1 3,  Antonio Delgado 1 2
Affiliations

Affiliations

  • 1 Spanish National Research Council (CSIC), Institute for Advanced Chemistry of Catalonia (IQAC-CSIC) , Research Unit on Bioactive Molecules (RUBAM), Department of Biological Chemistry , Jordi Girona 18-26 , 08034 Barcelona , Spain.
  • 2 University of Barcelona (UB) , Faculty of Pharmacy, Department of Pharmacology, Toxicology and Medicinal Chemistry, Unit of Pharmaceutical Chemistry (Associated Unit to CSIC) , Avda. Joan XXIII s/n , 08028 Barcelona , Spain.
  • 3 Centro de Investigación Biomédica en Red (CIBEREHD) , 28029 Madrid , Spain.
  • 4 University of Jaén , Faculty of Experimental Sciences, Department of Physical and Analytical Chemistry , Campus Las Lagunillas , 23071 Jaén , Spain.
PMID: 31860798 DOI: 10.1021/acs.joc.9b02420
Abstract

The synthesis of a series of vinylated analogues of sphingosine-1-phosphate together with their unambiguous configurational assignment by VCD methods is reported. Among them, compound RBM10-8 can irreversibly inhibit human sphingosine-1-phosphate lyase (hS1PL) while behaving also as an Enzyme substrate. These findings, together with the postulated mechanism for S1PL activity, reinforce the role of RBM10-8 as a new mechanism-based hS1PL inhibitor.

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