| Title: |
Synthesis and Characterization of Store-Operated Calcium Entry Inhibitors Active in the Submicromolar Range |
| Authors: |
Le Guilcher, Camille; Luyten, Tomas; Parys, Jan B.; Pucheault, Mathieu; Dellis, Olivier |
| Source: |
ISSN:1661-6596 ; ISSN:1422-0067 ; International Journal Of Molecular Sciences, vol. 21 (24), Art.No. ARTN 9777. |
| Publisher Information: |
Multidisciplinary Digital Publishing Institute (MDPI) |
| Publication Year: |
2020 |
| Subject Terms: |
Science & Technology; Life Sciences & Biomedicine; Physical Sciences; Biochemistry & Molecular Biology; Chemistry; Multidisciplinary; store-operated calcium entry; inhibitor; synthesis; apoptosis; INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR; 2-AMINOETHOXYDIPHENYL BORATE 2-APB; CA2+ RELEASE; 2-AMINOETHYLDIPHENYL BORATE; SECRETORY GRANULES; CHANNEL BLOCKERS; ORAI1; STIM1; POTENTIATION; ANALOGS; Boron Compounds; Calcium; Calcium Channel Blockers; Calcium Channels; Humans; Interleukin-2; Jurkat Cells; Phytohemagglutinins; 0399 Other Chemical Sciences; 0604 Genetics |
| Description: |
The store-operated calcium entry, better known as SOCE, forms the main Ca2+ influx pathway in non-excitable cells, especially in leukocytes, where it is required for cell activation and the immune response. During the past decades, several inhibitors were developed, but they lack specificity or efficacy. From the non-specific SOCE inhibitor 2-aminoethyl diphenylborinate (2-APB), we synthetized 16 new analogues by replacing/modifying the phenyl groups. Among them, our compound P11 showed the best inhibitory capacity with a Ki ≈ 75 nM. Furthermore, below 1 µM, P11 was devoid of any inhibitory activity on the two other main cellular targets of 2-APB, the IP3 receptors, and the SERCA pumps. Interestingly, Jurkat T cells secrete interleukin-2 under phytohemagglutinin stimulation but undergo cell death and stop IL-2 synthesis when stimulated in the presence of increasing P11 concentrations. Thus, P11 could represent the first member of a new and potent family of immunosuppressors. ; status: Published |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
https://lirias.kuleuven.be/handle/123456789/670121; https://doi.org/10.3390/ijms21249777; https://pubmed.ncbi.nlm.nih.gov/33371518 |
| DOI: |
10.3390/ijms21249777 |
| Availability: |
https://lirias.kuleuven.be/handle/123456789/670121; https://lirias.kuleuven.be/retrieve/328efb23-b108-4b57-aa23-b3ad0ce4da12; https://doi.org/10.3390/ijms21249777; https://pubmed.ncbi.nlm.nih.gov/33371518 |
| Rights: |
info:eu-repo/semantics/openAccess ; public |
| Accession Number: |
edsbas.9338405F |
| Database: |
BASE |