232935-92-1

WX8 (Ro 91-4714) is an ATP-competitive PIKFYVE inhibitor, with Kd values of 0.9 nM and 340 nM for PIKFYVE and PIP4K2C, respectively. WX8 (Ro 91-4714) inhibits lysosomal fission without effecting homotypic lysosomal fusion. WX8 (Ro 91-4714) is used in the research of autophagy-dependent cancer[1].

WX8 (Ro 91-4714) is a selective phosphoinositide kinase PIKfyve inhibitor th at disrupts lysosome fission via tubulationlysosomal traffickingand heterotypic lysosomes-autophagosomes fusion (0.1-1 μM; U2OS)but not homotypic lysosome fusion. WX8 exhibits cancer-selective antiproliferation activity (IC50 = 48 nM/A375200 nM/U2OS; IC50 >10 μM/non-cancer 293T & HFF) with a higher potency than the PIKfyve inhibitor YM201636or the lysosomal inhibitors chloroquine & hydroxychloroquine (A375 IC50 = 119 nM1.7 μM1.9 μMrepectively).

[1] Ajit Roy, et al. Selective Termination of Autophagy-Dependent Cancers. Cells. 2024 Jun 25;13(13):1096. DOI:10.3390/cells13131096
[2] Gaurav Sharma, et al. A family of PIKFYVE inhibitors with therapeutic potential against autophagy-dependent cancer cells disrupt multiple events in lysosome homeostasis. Autophagy. 2019 Oct;15(10):1694-1718. DOI:10.1080/15548627.2019.1586257