WYE-354 Chemical Properties

Density 

1.46

storage temp. 

Sealed in dry,Store in freezer, under -20°C

solubility 

≥49.6 mg/mL in DMSO; insoluble in H2O; insoluble in EtOH

form 

solid

pka

13.42±0.70(Predicted)

WYE-354 Usage And Synthesis

Description

WYE-354 is a potent cell-permeable inhibitor of mTOR (IC₅₀ = 4.3 nM) which blocks signaling through both mTOR complex 1 (mTORC1) and mTORC2. It is a much weaker inhibitor of phosphatidylinositol 3-kinase α (IC₅₀ = 1,026 nM) and other kinases. WYE-354 induces G₁ cell cycle arrest in both rapamycin-sensitive and rapamycin-resistant cancer cell lines, inhibits mTORC1 and mTORC2 in tumor-bearing mice, and reduces tumor growth in nude mice with PTEN-null tumors.

Uses

A pyrazolopyrimidines derivative that is a potent and ATP-competitive mTOR inhibitor with much reduced activity against PI 3-Kα or PI 3-Kγ. WYE-354 is equally potent against mTORC1 and mTORC2 activities in HEK293 immune complex kinase assays using S6K and Akt as the respective substrate (IC50 <200 nM; [ATP] = 100 μM) and effectively blocks cellular phosphorylation of S6K on T389 and Akt on S473 both in cultures and in a murine xenograft model, resulting in a significant suppression of PC3MM2-derived tumor growth (by 86% on day 7; 50 mg/kg, i.p twice per day) in vivo.

Definition

ChEBI: 4-[6-[4-(methoxycarbonylamino)phenyl]-4-(4-morpholinyl)-1-pyrazolo[3,4-d]pyrimidinyl]-1-piperidinecarboxylic acid methyl ester is a carbamate ester.

target

mTOR

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.

WYE-354(1062169-56-5)Related Product Information

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• N-[4-[1-(1,4-Dioxaspiro[4.5]dec-8-yl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-N'-methylurea
• WYE-687
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• KU-0063794
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