Chemdea
 
작성일 : 14-01-13
[Chemdea] mTOR selective inhibitors (1)
AZD8055 / Ku-0063794 / Pp242 (TORKinib) / WYE-132 / WYE-125132 - sub-nanomolar mTOR Inhibitor
 
mTOR selective inhibitors (1)
 
 
Product Name: AZD8055 – mTOR Inhibitor
 
   클릭하시면 닫힙니다.이미지 저장을 원하시면 마우스 오른쪽클릭후 '다른이름으로 저장'을 하세요
 
AZD8055 is a novel ATP-competitive inhibitor of mTOR kinase (both complexes mTORC1 and mTORC2) with an IC50 of
0.8 nM. It shows 1000 fold selectivity against all PI3K isoforms and other members of the PI3K-like family. Furthermore
AZD8055 does not show significant activity against a 260-membered kinase panel (IC50 > 10 mM). AZD8055 inhibits the
phosphorylation of mTORC1 substrates p70S6K and 4E-BP1 as well as phosphorylation of the mTORC2 substrate AKT and downstream proteins. The rapamycin-resistant T37/46 phosphorylation sites on 4E-BP1 were fully inhibited by
AZD8055, resulting in significant inhibition of cap-dependent translation. In vitro, AZD8055 potently inhibits proliferation
and induces autophagy in H838 and A549 cells. In vivo, AZD8055 induces a dose-dependent pharmacodynamic effect
on phosphorylated S6 and phosphorylated AKT at plasma concentrations leading to tumor growth inhibition. Notably, 
AZD8055 results in significant growth inhibition and/or regression in xenografts, representing a broad range of human
tumor types.
 
Details
Chemical Formula:
 
C25H31N5O4
CAS No.:
 
1009298-09-2
Molecular weight:
 
465.56
Purity:
99% by HPLC
Appearance:
 
Yellow solid
Chemical name:
 
 5-[2,4-Bis[(3S)-3-methyl-4-morpholinyl]pyrido[2,3-d]pyrimidin-7-yl]-2-
methoxybenzenemethanol
Solubility:
 
DMSO (100mg/mL)
Storage:
Protect from light. Packaged under inert gas
 
References
 
 
Product Name: Ku-0063794 mTOR Inhibitor
 
   클릭하시면 닫힙니다.이미지 저장을 원하시면 마우스 오른쪽클릭후 '다른이름으로 저장'을 하세요
 
Ku-0063794  inhibits both mTORC1 and mTORC2 with an IC50 of ∼10 nM, but does not suppress the activity of 76
other protein kinases or seven lipid kinases, including Class 1 PI3Ks at 1000-fold higher concentrations. Ku-0063794 is
cell permeant, suppresses activation and hydrophobic motif phosphorylation of Akt, S6K and SGK, but not RSK
(ribosomal S6 kinase). Ku-0063794 also suppressed cell growth and induced a G1-cell-cycle arrest. Ku-0063794 is a
prototype of mTOR inhibitor AZD8055 currently in Phase I/II trial in Advance Solid Tumors, Lymphoma and Endometrial
Carcinoma.
 
Details
Chemical Formula:
 
C25H31N5O4
CAS No.:
 
1938440-64-3
Molecular weight:
 
465.5
Purity:
99% by HPLC
Appearance:
 
Pale yellow solid
Chemical name:
 
rel-5-[2-[(2R,6S)-2,6-Dimethyl-4-morpholinyl]-4-(4-morpholinyl)pyrido[2,3-d]pyrimidin-7-yl]-2-methoxybenzenemethanol
Solubility:
 
DMSO (15mg/mL)
Storage:
Protect from light. Packaged under inert gas
 
References
 
 
Product Name: Pp242 (TORKinib) – mTOR Inhibitor
 
   클릭하시면 닫힙니다.이미지 저장을 원하시면 마우스 오른쪽클릭후 '다른이름으로 저장'을 하세요
 
A cell-permeable pyrazolopyrimidine compound that acts as a potent, reversible, and ATP-competitive inhibitor against
both mTORC1 & mTORC2 (IC50 = 30 & 58 nM, respectively, with 100 µM ATP). PP242 inhibits PKCα, p110γ, and JAK2
with 6-, 13-, and 14-fold less potency and exhibits much reduced or no activity against a panel of 216 other kinases at a
concentration of 1 µM (maximum of 68% or 77% inhibition observed with 10 or 100 µM ATP, respectively). PP242 
differentially inhibits insulin-stimulated phosphorylations of cellular proteins both in cultures (2.5 µM) in vitro and in
mice (20 mg/kg i.p.) in vivo in a manner distinctly different from that seen in mTORC2-functional knockout SIN1-/- cells
or in cultures treated with Rapamycin, which targets only mTORC1, but not mTORC2. Blockage of 4EBP1 T36/T45/S65
phosphorylation by PP242 upon insulin stimulation in primary MEFs correlates well with an enhanced 4EBP1 
association with the cap-
binding protein eIF4E, resulting in a selective inhibition of cap-dependent, but not cap-independent, protein
translation.
 
Details
Chemical Formula:
 
C16H16N6O
CAS No.:
 
1938440-64-3
Molecular weight:
 
308.3
Purity:
99% by HPLC
Appearance:
 
White to off white solid
Chemical name:
 
2-(4-Amino-1-isopropyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-1H-indol-5-ol
Solubility:
 
DMSO (10mg/mL)
Storage:
Protect from light. Packaged under inert gas
 
References
 
 
Product Name: WYE-132 / WYE-125132 – sub-nanomolar mTOR Inhibitor
 
   클릭하시면 닫힙니다.이미지 저장을 원하시면 마우스 오른쪽클릭후 '다른이름으로 저장'을 하세요
 
WYE-132 (WYE-125132) is a highly potent, ATP-competitive, and specific mTOR kinase inhibitor (IC50 = 0.19 nM; >5,000-
fold selective versus PI3Ks). WYE-132 inhibited mTORC1 and mTORC2 in diverse cancer models in vitro and in vivo. WYE-132 targeted P-AKT(S473) and AKT function without significantly reducing the steady-state level of the PI3K/PDK1
activity biomarker P-AKT(T308), highlighting a prominent and direct regulation of AKT by mTORC2 in cancer cells.
Compared with the rapalog temsirolimus/CCI-779, WYE-132 elicited a substantially stronger inhibition of cancer cell
growth and survival, protein synthesis, cell size, bioenergetic metabolism, and adaptation to hypoxia. Oral administration of WYE-132 to tumor-bearing mice showed potent single-agent antitumor activity against MDA361 breast, U87MG glioma,
A549 and H1975 lung, as well as A498 and 786-O renal tumors. An optimal dose of WYE-132 achieved a substantial
regression of MDA361 and A549 large tumors and caused complete regression of A498 large tumors when co-
administered with bevacizumab.
 
Details
Chemical Formula:
 
C27H33N7O4
CAS No.:
 
1144068-46-1
Molecular weight:
 
519.60
Purity:
99% by HPLC
Appearance:
 
White solid
Chemical name:
 
1-{4-[1-(1,4-Dioxa-spiro[4.5]dec-8-yl)-4-(8-oxa-3-aza-bicyclo[3.2.1]oct-3-yl)-1H-pyrazolo
[3,4-d] pyrimidin-6-yl]-phenyl}-3-methyl-urea
Solubility:
 
DMSO (50mg/mL)
Storage:
Protect from light. Packaged under inert gas
 
References
 
Ordering informations
 
Catalog No.
Product Name
Size
CD0348
AZD8055 – mTOR Inhibitor
1 mg, 5 mg, 10 mg, 25 mg,
50 mg, 100 mg & 200 mg
CD0274
Ku-0063794 mTOR Inhibitor
1 mg, 5 mg, 10 mg, 25 mg,
50 mg, 100 mg, 200 mg & 1 g
CD0258
Pp242 (TORKinib) – mTOR Inhibitor
1 mg, 5 mg, 10 mg, 25 mg,
50 mg, 100 mg, 250 mg & 1 g
CD0325
WYE-132 / WYE-125132 – sub-nanomolar mTOR Inhibitor
1 mg, 5 mg, 10 mg, 25 mg,
50 mg & 100 mg
 
 
▣ 관련 페이지 ; Chemdea