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#: 1144068-46-1

ChemicalBook > Product Catalog > Biochemical Engineering > Inhibitors > PI3K / Akt / mTOR > mTOR inhibitors > 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

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

Basic information Safety Supplier Related

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 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:

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
WYE-125132 (WYE-132);WYE-125132;WYE 125132; WYE125132

CAS:

1144068-46-1

MF:

C27H33N7O4

MW:

519.6

Product Categories:

mTOR
PI3K
PI3K/Akt/mTOR
Inhibitors
Akt

Mol File:

1144068-46-1.mol

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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 Chemical Properties

Melting point:: 162-184°C (dec.)
Density: 1.55
storage temp.: -20°C Freezer
solubility: DMSO (Slightly)
form: White powder solid.
pka: 13.82±0.46(Predicted)
color: Off-White to Pale Beige

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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 Usage And Synthesis

Uses

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

Definition

ChEBI: 1-[4-[1-(1,4-dioxaspiro[4.5]decan-8-yl)-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-6-pyrazolo[3,4-d]pyrimidinyl]phenyl]-3-methylurea is a member of ureas.

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].

in vivo

A single i.v. administration of 50 mg/kg WYE-132 (WYE-125132) into tumor-bearing mice leads to suppression of P-S6K(T389) and P-AKT(S473) for at least 8 hours in PC3MM2, MDA361, HCT116, and HT29 tumors, whereas the steady-state level of P-AKT(T308) is not significantly reduced, indicating that the antitumor efficacy of WYE-132 under such dosing regimens reflects the suppression of mTOR rather than PI3K. Oral administration of WYE-132 causes dose-dependent tumor growth delay in the PI3K/mTOR- and HER2-hyperactive MDA361 tumors with significant antitumor activity at 5 mg/kg, which correlates with a suppression P-S6 and P-AKT(S473) but not P-AKT(T308). An optimal dose of 50 mg/kg WYE-132 induces a substantial regression of large MDA361 tumors. WYE-132 also causes a potent and substantial tumor growth delay in the PTEN-null U87MG glioma^[1].

target

mTOR

IC 50

mTOR: 0.19 nM (IC₅₀); mTORC1; mTORC2; PI3Kα: 1.179 μM (IC₅₀); PI3Kδ: 2.38 μM (IC₅₀); hSMG1: 1.25 μM (IC₅₀)

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.

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'-methylureaSupplier

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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(1144068-46-1)Related Product Information