mTOR selective inhibitors (1)
본문
mTOR selective inhibitors (1)
Product Name: AZD8055 – mTOR Inhibitor
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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.
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Details
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Chemical Formula:
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C25H31N5O4
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CAS No.:
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1009298-09-2
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Molecular weight:
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465.56
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Purity:
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99% by HPLC
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Appearance:
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Yellow solid
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Chemical name:
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5-[2,4-Bis[(3S)-3-methyl-4-morpholinyl]pyrido[2,3-d]pyrimidin-7-yl]-2- methoxybenzenemethanol
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Solubility:
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DMSO (100mg/mL)
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Storage:
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Protect from light. Packaged under inert gas
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References
Product Name: Ku-0063794 – mTOR Inhibitor
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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.
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Details
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Chemical Formula:
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C25H31N5O4
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CAS No.:
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1938440-64-3
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Molecular weight:
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465.5
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Purity:
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99% by HPLC
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Appearance:
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Pale yellow solid
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Chemical name:
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rel-5-[2-[(2R,6S)-2,6-Dimethyl-4-morpholinyl]-4-(4-morpholinyl)pyrido[2,3-d]pyrimidin-7-yl]-2-methoxybenzenemethanol
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Solubility:
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DMSO (15mg/mL)
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Storage:
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Protect from light. Packaged under inert gas
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References
Product Name: Pp242 (TORKinib) – mTOR Inhibitor
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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.
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Details
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Chemical Formula:
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C16H16N6O
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CAS No.:
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1938440-64-3
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Molecular weight:
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308.3
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Purity:
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99% by HPLC
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Appearance:
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White to off white solid
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Chemical name:
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2-(4-Amino-1-isopropyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-1H-indol-5-ol
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Solubility:
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DMSO (10mg/mL)
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Storage:
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Protect from light. Packaged under inert gas
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References
Product Name: WYE-132 / WYE-125132 – sub-nanomolar mTOR Inhibitor
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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.
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Details
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Chemical Formula:
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C27H33N7O4
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CAS No.:
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1144068-46-1
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Molecular weight:
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519.60
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Purity:
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99% by HPLC
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Appearance:
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White solid
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Chemical name:
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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
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Solubility:
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DMSO (50mg/mL)
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Storage:
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Protect from light. Packaged under inert gas
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References
Ordering informations
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Catalog No.
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Product Name
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Size
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CD0348
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AZD8055 – mTOR Inhibitor
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1 mg, 5 mg, 10 mg, 25 mg,
50 mg, 100 mg & 200 mg
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CD0274
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Ku-0063794 – mTOR Inhibitor
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1 mg, 5 mg, 10 mg, 25 mg,
50 mg, 100 mg, 200 mg & 1 g
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CD0258
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Pp242 (TORKinib) – mTOR Inhibitor
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1 mg, 5 mg, 10 mg, 25 mg,
50 mg, 100 mg, 250 mg & 1 g
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CD0325
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WYE-132 / WYE-125132 – sub-nanomolar mTOR Inhibitor
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1 mg, 5 mg, 10 mg, 25 mg,
50 mg & 100 mg
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▣ 관련 페이지 ; Chemdea
- 이전글mTOR Selective inhibitors (2) 14.01.13
- 다음글ATM ligands, KU-55933 - ATM Kinase Inhibitor 14.01.10
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