533557 AKT Inhibitor XXIII, Isozyme-Selective, GSK2141795 - CAS 1047634-65-0 - Calbiochem

533557
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      Overview

      Replacement Information

      Key Specifications Table

      Empirical FormulaCAS #
      C₁₈H₁₆Cl₂F₂N₄O₂ 1047634-65-0

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      5.33557.0001
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          Glass bottle 5 mg
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          Description
          OverviewA cell-permeable, orally available, and non-toxic pyrazolylfuran-carboxamide derived compound that acts as a highly potent, ATP-competitive, and reversible inhibitor of Akt1, Akt2, Akt3 (IC50 = 66 pM, 1.4 nM, and 1.5 nM, respectively). Shown to block the phosphorylation of multiple Akt substrates. Also shown to be a highly effective inhibitor of E17K mutant form of Akt1 (IC50 = 200 pM). Inhibits the activity of PKA, PKG1α, and PKG1β (IC50 = 2, <1, and <1 nM, respectively), but shows high selectivity over a wide panel of other protein kinases. Modestly inhibits several PKC isozymes at much higher concentrations (IC50 = 90 nM). Induces cell cycle arrest at G1 phase and causes apoptosis in BT474, LNCaP, A3, and 19.2 cell lines (~ 1 µM). Suppresses the growth of BT474 xenograft tumors in mice (98% at 30 mg/kg; 57% at 20 mg/kg, p.o. q.d x 21 days). Also induces a transient increase in blood glucose and corresponding insulin levels (200 mg/dl and 188 ng/ml, respectively with a single dose of 30 mg/kg).

          Please note that the molecular weight for this compound is batch-specific due to variable water content. Please refer to the vial label or the certificate of analysis for the batch-specific molecular weight. The molecular weight provided represents the baseline molecular weight without water.
          Catalogue Number533557
          Brand Family Calbiochem®
          SynonymsGSK 2141795, Uprosertib
          References
          ReferencesDumble, M., et al. 2014. PLoS One. 9, e100880.
          Product Information
          CAS number1047634-65-0
          FormOff-white solid
          Hill FormulaC₁₈H₁₆Cl₂F₂N₄O₂
          Chemical formulaC₁₈H₁₆Cl₂F₂N₄O₂
          ReversibleY
          Applications
          Biological Information
          Primary TargetAkt1
          Secondary targetAkt2, Akt3
          Purity≥98% by HPLC
          Physicochemical Information
          Cell permeableY
          Dimensions
          Materials Information
          Toxicological Information
          Safety Information according to GHS
          Safety Information
          Product Usage Statements
          Storage and Shipping Information
          Ship Code Ambient Temperature Only
          Toxicity Standard Handling
          Storage +2°C to +8°C
          Protect from Light Protect from light
          Do not freeze Ok to freeze
          Special InstructionsFollowing reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.
          Packaging Information
          Packaged under inert gas Packaged under inert gas
          Transport Information
          Supplemental Information
          Specifications

          Documentation

          AKT Inhibitor XXIII, Isozyme-Selective, GSK2141795 - CAS 1047634-65-0 - Calbiochem SDS

          Title

          Safety Data Sheet (SDS) 

          References

          Reference overview
          Dumble, M., et al. 2014. PLoS One. 9, e100880.
          Data Sheet

          Note that this data sheet is not lot-specific and is representative of the current specifications for this product. Please consult the vial label and the certificate of analysis for information on specific lots. Also note that shipping conditions may differ from storage conditions.

          Revision20-November-2015 JSW
          SynonymsGSK 2141795, Uprosertib
          DescriptionA cell-permeable pyrazolylfuran-carboxamide derived compound that is reported to inhibit Akt kinase activity in a reversible, ATP-competitive, and Akt1-selective manner (Ki = 0.066 nM/Akt1, 1.4 nM/Akt2, 1.5 nM/Akt3) with additional inhibitory activity against PKA & PKG (IC50 = 2.0 nM/PKA and <1 nM/PKG1α & PKG1β), while exhibiting much reduced potency toward p70S6K, ROCK, RSK1 (IC50 = 50, 126, 200 nM, respectively), and 11 PKC isoforms (IC50 in nM = 49/η, 56/β1, 64/θ, 69/δ, 86/β2, 200/γ, 690/μ, >1000/α, ε, ι, & ζ). Shown to inhibit cellular phosphorylation levels of Akt substrates, including GSK-3β Thr9, PRAS40 Thr246 (IC50 in nM against pGSK-3&beta/pPRAS40 = 34/55 in LNCaP and 143/39 in BT474 cells post 1 h drug treatment), Caspase-9 Ser196, and FOXO Thr24/32, effectively inducing FOXO nuclear localization (EC50 = 47 nM toward GFP-FOXO3a nuclear localization in MDA-MG-468 post 1 h drug treatment) without affecting MEK Ser217/221 or ERK Tyr204 phosphorylation even at 10 µM concentration. Cancer panel antiproliferation study reveals many GSK2141795-sensitive cell lines (IC50 <1 µM by viability assay based on cellular ATP content post 3-day drug treatment) contain PI3K or PTEN alternations, while many resistant lines (IC50 >1 µM) contain BRAF, KRAS, or NRAS mutations. Shown to suppress human breast carcinoma BT474 & ovarian carcinoma SKOV3 tumor growth in mice (%suppression/dose/cancer = 57/20 mg kg-1/BT474, 98/30 mg kg-1/BT474, 85/20 mg kg-1/SKOV3, 93/30 mg kg-1/SKOV3 following 21 daily oral dosages) in vivo with good tumor tissue drug exposure and concomitant tumor PRAS40 phosphorylation reduction (63% pPRAS40 reduction 2 h post 7 daily 30 mg kg-1 oral dosages; [drug] = 1.6 µg/mL plasma & 12.6 µg/mg BT474 tumor), while, unlike many other Akt inhibitors, displaying much reduced perturbation of glucose homeostasis. Effective suppression of pancreatic adenocarcinoma is demonstrated with combined GSK2141795 & MEK inhibitor treatment of mice bearing HPAC or Capan-2 tumor.
          FormOff-white solid
          Intert gas (Yes/No) Packaged under inert gas
          CAS number1047634-65-0
          Chemical formulaC₁₈H₁₆Cl₂F₂N₄O₂
          Purity≥98% by HPLC
          SolubilityDMSO (50 mg/ml)
          Storage +2°C to +8°C
          Protect from light
          Do Not Freeze Ok to freeze
          Special InstructionsFollowing reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.
          Toxicity Standard Handling
          ReferencesDumble, M., et al. 2014. PLoS One. 9, e100880.