1144068-46-1

Basic information

• Product Name: 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
• Synonyms: 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 125132;WYE 125132(WYE-132);1-(4-(4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-1-(1,4-dioxaspiro[4.5]decan-8-yl)-1H-pyrazolo[3,4-d]pyriMidin-6-yl)phenyl)-3-Methylurea;WYE125132/WYE-125132/WYE-132;Urea, 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'-methyl-;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 WYE125132(WYE-132);WYE 125132 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
• CAS NO: 1144068-46-1
• Molecular Formula: C₂₇H₃₃N₇O₄
• Molecular Weight: 519.59542
• Product Categories: PI3K/Akt/mTOR;Inhibitors;Akt;mTOR;PI3K
• Mol File: 1144068-46-1.mol
• Article Data: 2

Chemical Properties

• Appearance: /
• Density: 1.55
• Storage Temp.: -20°C Freezer
• Solubility: DMSO (Slightly)
• PKA: 13.82±0.46(Predicted)
• CAS DataBase Reference: 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(CAS DataBase Reference)
• NIST Chemistry Reference: 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(1144068-46-1)
• EPA Substance Registry System: 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(1144068-46-1)

Safety Data

• Hazardous Substances Data: 1144068-46-1(Hazardous Substances Data)

Usage

Uses

WYE-125132 is a highly potent, ATP-competitive and specific mammalian target of rapamycin (mTOR) inhibitor.

Biological Activity

wye-125132 (wye-132) is highly potent, atp-competitive, and specific inhibitor of mtor kinase with ic50 value of 0.19±0.07nmol/l, ＞5000-fold selective versus pi3ks [1].wye-125132 (wye-132) has been reported to mtorc1-dependent phosphorylation of s6k (t389) and mtorc2-dependent phos-phorylation of akt (s473) in immune-complex assay. in addition, in insulin-like growth factor-i(igf-i)–induced rat1, the pik3ca mutant mda361, or pten-null u87mg cells, wye-125132 (wye-132) has also been revealed to dose-dependently inhibit p-s6k(t389) and p-akt(s473) with ec50 in low nanomolar range. apart from these, wye-125132 (wye-132) has shown a potent anti-proliferative agent against mda361, pc3mm2, u87mg, a549, and hct116 cell lines. moreover, wye-125132 (wye-132) has noted a stronger inhibition of protein synthesis and cell size in mda361 and hek293 cell lines [1].

references

[1] yu k1, shi c, toral-barza l, lucas j, shor b, kim je, zhang wg, mahoney r, gaydos c, tardio l, kim sk, conant r, curran k, kaplan j, verheijen j, ayral-kaloustian s, mansour ts, abraham rt, zask a, gibbons jj. beyond rapalog therapy: preclinical pharmacology and antitumor activity of wye-125132, an atp-competitive and specific inhibitor of mtorc1 and mtorc2. cancer res. 2010 jan 15;70(2):621-31. doi: 10.1158/0008-5472.can-09-2340. epub 2010 jan 12.

Upstream product

• 32315-10-9 bis(trichloromethyl) carbonate 
• 1144068-84-7 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]aniline 
• 74-89-5 methylamine 

Downstream Products

• 1144068-48-3 1-methyl-3-{4-[4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1-(4-oxocyclohexyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}urea 

Relevant articles and documents

Pyrazolopyrimidines as highly potent and selective, ATP-competitive inhibitors of the mammalian target of rapamycin (mTOR): Optimization of the 1-substituent

A series of pyrazolopyrimidine mammalian Target Of Rapamycin (mTOR) inhibitors with various substituents at the 1-position have been prepared, resulting in compounds with excellent potency, selectivity and microsomal stability. Combination of a 1-cyclohexyl ketal group with a 2,6-ethylene bridged morpholine in the 4-position and a ureidophenyl group in the 6-positon resulted in compound 8a, that selectively suppressed key mTOR biomarkers in vivo for at least 8 h following iv administration and showed excellent oral activity in a xenograft tumor model.