1H-Indole-3-carboxaldehyde, 2-[4-(4-morpholinyl)-6-(phenylamino)-1,3,5-triazin-2-yl]hydrazone

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 tubulation, lysosomal trafficking, and heterotypic lysosomes-autophagosomes fusion (0.1-1 μM; U2OS), but not homotypic lysosome fusion. WX8 exhibits cancer-selective antiproliferation activity (IC50 = 48 nM/A375, 200 nM/U2OS; IC50 >10 μM/non-cancer 293T & HFF) with a higher potency than the PIKfyve inhibitor YM201636, or the lysosomal inhibitors chloroquine & hydroxychloroquine (A375 IC50 = 119 nM, 1.7 μM, 1.9 μM, repectively).

[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