WYE-354 is a powerful and selective ATP-competitive kinase heterocyclic inhibitors with biochemical IC50 of 5 nM against mTOR.[1]
WYE-354 displays very specific selectivity to PI3K families (>100-fold to PI3K and >500-fold to PI3K), but it can’t inhibit some protein kinases. May cancer cell lines including MDA-MB-468 and U87MG can be inhibited by WYE-354 in 0.3–1 mM range.[1]
In-vitro study has proved that WYE-354 can inhibit substrate phosphorylation such as p-4E-BP1 T37/46 and p-Akt S473 by mTORC1 and mTORC2. WYE-354 can reduce Akt downstream function and block the propagation of the cancer cell lines with an IC50 value from sub-micromolar to micromolar range [3]. These effects were consistent with the G1 cell cycle arrest in two cell lines, including rapamycin-sensitive and rapamycin-resistant cells. It is believed to induce apoptosis, repress the global protein synthesis, and down-regulate many angiogenic factors.[3]
References:
[1] Qingsong Liu, Carson Thoreen, Jinhua Wang, David Sabatini, Nathanael S. Gray. mTOR mediated anti-cancer drug discovery. Drug Discovery Today. 2009. 6(2): 47-55.
[2] Shi-Yong Sun. mTOR kinase inhibitors as potential cancer therapeutic drugs. Cancer Letters. 28 October 2013. 340(1): 1-8.