International Journal of Molecular Sciences p. 1 - 23 (2020)
Update date:2022-08-06
Topics:
Guilcher, Camille Le
Luyten, Tomas
Parys, Jan B.
Pucheault, Mathieu
Dellis, Olivier
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.
View MoreContact:+65 9658 0999
Address:26 Sin Ming Lane, Midview City, #05-118, Singapore 573971
Contact:18698110882
Address:1303 No2 building,LuoMa Garden,YongAn Road,Hexi District,Tianjin city
Buffett (China) Holding Co.,Ltd
Contact:4006570891
Address:
Shanghai Massive Chemical Technology Co., Ltd.
website:http://www.massivechem.com/
Contact:+86 21 34943721
Address:Room 435, 4th floor, Building 9, No. 2568 Gudai Road,Minhang District, Shanghai,
Wuhan Hanye Chemical New Material Co.,Ltd
Contact:+86-27-85308141
Address:LiuDian, Panlongcheng Economic Development Zone, HuangPi district, Wuhan, Hubei 430311 P.R.China
Doi:10.3390/molecules24112081
(2019)Doi:10.1021/jo01363a037
(1957)Doi:10.1016/S0040-4020(01)90087-0
(1990)Doi:10.1021/jo00005a012
(1991)Doi:10.1016/j.carres.2011.03.008
(2011)Doi:10.1021/jo00035a040
(1992)