1. PI3K/Akt/mTOR
    Autophagy
  2. mTOR
    Autophagy
  3. OSI-027

OSI-027 (Synonyms: ASP7486)

Cat. No.: HY-10423 Purity: 99.40%
Handling Instructions

OSI-027 (ASP7486) est un inhibiteur de l'activité kinase mTOR qui est puissant, sélectif, oralement actif et ATP-compétitif avec un IC50 de 4 nM. OSI-027 cible mTORC1 et mTORC2 avec des IC50s de 22 nM et 65 nM, respectivement.

OSI-027 (ASP7486) is a potent, selective, orally active and ATP-competitive mTOR kinase activity inhibitor with an IC50 of 4 nM. OSI-027 targets both mTORC1 and mTORC2 with IC50s of 22 nM and 65 nM, respectively.

For research use only. We do not sell to patients.

OSI-027 Chemical Structure

OSI-027 Chemical Structure

CAS No. : 936890-98-1

Size Price Stock Quantity
Free Sample (0.5-1 mg)   Apply Now  
10 mM * 1 mL in DMSO USD 119 In-stock
Estimated Time of Arrival: December 31
5 mg USD 108 In-stock
Estimated Time of Arrival: December 31
10 mg USD 210 In-stock
Estimated Time of Arrival: December 31
50 mg USD 576 In-stock
Estimated Time of Arrival: December 31
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Customer Review

Based on 11 publication(s) in Google Scholar

Top Publications Citing Use of Products

    OSI-027 purchased from MCE. Usage Cited in: EBioMedicine. 2015 Nov 19;2(12):1944-56.

    SW620 xenograft tumors are treated with SB202190 and OSI027 individually or in combination. The effect on signaling by p38 (P-MK2 and P-Hsp27) and mTOR (P-S6K1 and P-AKT) is analyzed by immunoblot. SB202190 achieves on-target inhibition by diminishes phosphorylation of MK2 and Hsp27. OSI-027 blocks signaling by both mTORC1 and mTORC2 by decreases phosphorylation of S6K1 and AKT. When SB202190 and OSI-027 are used in combination, all three kinases, p38, mTORC1 and mTORC2 are potently inhibited.

    OSI-027 purchased from MCE. Usage Cited in: Oncotarget. 2017 Feb 21;8(8):12775-12783.

    OSI-027, AZD-8055 and AZD-2014 almost completely block MHY1485-induced mTOR activation (p-mTOR/S6K1/Akt Ser473) in skin keratinocytes.

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    • Biological Activity

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    • Customer Review

    Description

    OSI-027 (ASP7486) is a potent, selective, orally active and ATP-competitive mTOR kinase activity inhibitor with an IC50 of 4 nM. OSI-027 targets both mTORC1 and mTORC2 with IC50s of 22 nM and 65 nM, respectively[1][2].

    IC50 & Target

    mTOR

    4 nM (IC50)

    mTORC1

    22 nM (IC50)

    mTORC2

    65 nM (IC50)

    PI3K-γ

    0.42 μM (IC50)

    PI3K-α

    1.3 μM (IC50)

    DNA-PK

    1 μM (IC50)

    Autophagy

     

    In Vitro

    OSI-027 is an ATP-competitive inhibitor, which targets both mTORC1 and mTORC2 with IC50s of 22 nM and 65 nM. OSI-027 also inhibits PI3K-α, PI3K-γ and DNA-PK with IC50s of 1.3 μM, 0.42 μM and 1.0 μM. OSI-027 inhibits mTOR signaling of phospho-4E-BP1 with an IC50 of 1 μM[1].

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    In Vivo

    Effects on GEO colorectal xenograft growth treated with Rapamycin or OSI-027 for 12 days are consistent with our in vitro experiments. Treatment with Rapamycin (20 mg/kg) inhibits phospho-S6 and phospho-4E-BP1, while Akt phosphorylation is increased by 29%. In contrast, OSI-027 (65 mg/kg) inhibits both mTORC1 and mTORC2 effectors. After 2 hours, decreased 4E-BP1, Akt, and S6 phosphorylation is observed and inhibition of S6 and Akt is sustained for 24 hours. The plasma drug concentration of OSI-027 inversely correlated with these effects on mTORC1 and mTORC2 signaling. The median plasma drug concentration with OSI-027 is 21.3 μM at 2 hours and 14.9 μM at 8 hours. The in vivo efficacy of OSI-027 plus Sunitinib is tested in H292 human lung and Ovcar-5 human ovarian xenograft tumors. H292 tumors, treated with OSI-027 (50 mg/kg) for 21 days have 61% median tumor growth inhibition for the duration of treatment (TGI). Sunitinib (40 mg/kg) for 21 days had 47% median TGI. Combining OSI-027 with Sunitinib, however, has a median TGI of 100% with 59% maximal tumor regression, a statistically significant improvement over either agent alone. Ovcar-5 xenograft tumors treated with OSI-027 or Sunitinib have a 55% and 68% median TGI, respectively. OSI-027 administered with Sunitinib has a significantly better median TGI of 100% with 38% maximal tumor regression[1].
    In the Rapamycin (RAPA) group, three rats exhibit symptoms typical of LTx-aGVHD and die 27 to 35 days after liver transplantation (LT); the remaining five rats do not develop LTx-aGVHD symptoms and survive for more than 100 days. In contrast, seven rats in the OSI-027 group survive for more than 100 days without symptoms of LTx-aGVHD, and only one rat exhibits LTx-aGVHD symptoms and dies on day 33 after LT[3].

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Clinical Trial
    Molecular Weight

    406.44

    Formula

    C₂₁H₂₂N₆O₃

    CAS No.

    936890-98-1

    SMILES

    O=C([[email protected]]1CC[[email protected]](C2=NC(C(N3)=CC4=C3C(OC)=CC=C4)=C5C(N)=NC=NN52)CC1)O

    Shipping

    Room temperature in continental US; may vary elsewhere.

    Storage
    Powder -20°C 3 years
    In solvent -80°C 6 months
    -20°C 1 month
    Solvent & Solubility
    In Vitro: 

    DMSO : ≥ 100 mg/mL (246.04 mM)

    H2O : < 0.1 mg/mL (insoluble)

    *"≥" means soluble, but saturation unknown.

    Preparing
    Stock Solutions
    Concentration Solvent Mass 1 mg 5 mg 10 mg
    1 mM 2.4604 mL 12.3019 mL 24.6039 mL
    5 mM 0.4921 mL 2.4604 mL 4.9208 mL
    10 mM 0.2460 mL 1.2302 mL 2.4604 mL
    *Please refer to the solubility information to select the appropriate solvent.
    In Vivo:
    • 1.

      Add each solvent one by one:  10% DMSO    40% PEG300    5% Tween-80    45% saline

      Solubility: ≥ 2.5 mg/mL (6.15 mM); Clear solution

    • 2.

      Add each solvent one by one:  10% DMSO    90% (20% SBE-β-CD in saline)

      Solubility: 2.5 mg/mL (6.15 mM); Suspended solution; Need ultrasonic

    *All of the co-solvents are provided by MCE.
    References
    Kinase Assay
    [1]

    Assays of a panel of 40 other recombinant kinases including both protein and lipid kinases are performed at 100 mM ATP concentration by SelectScreen profiling service. A broad panel of kinases is tested at a single concentration of OSI-027 or OXA-01 (3 μM) to evaluate percent inhibition of each kinase or mutant variant, using the Ambit KinomeScan platform[1].

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Cell Assay
    [1]

    To study the effect of drug treatment on cellular signaling, Ovcar-3 cells are plated in normal growth medium. After 24 hours, serum is removed and cells are serum-starved overnight. Rapamycin, OSI-027 and OXA-01 are solubilized in DMSO and added to cells at varying concentrations. After a two-hour incubation cells are growth factor stimulated with 10 ng/mL Insulin for 3 to 5 minutes, then rinsed with cold PBS and lysed[1].

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Animal Administration
    [1]

    Mice[1]
    For xenograft models, cells are harvested, implanted s.c. in the right flank of nu/nu CD-1 mice and tumor growth is analyzed. Mice bearing GEO xenografts are treated for 12 days with OSI-027 (65mg/kg) or vehicle and tumors collected at 2, 8, and 24 hours. Tumor growth inhibition and regression calculations are included.
    Rats[2]
    Specific pathogen-free female Lewis rats, male BN rats, male Lew-Tg(CAG-EGFP)YsRrrc rats and male Lew-TgYsRrrc rats are used. Orthotopic LT is undertaken. No antibiotics were used. Freshly prepared splenocytes (4×108, suspended in 500 μL PBS) of Lew-Tg YsRrrc rats are infused into each recipient via the dorsal penile vein immediately after LT (within 30 min). LTx-aGVHD model rats are divided into three experimental groups: RAPA (1 mg/kg), OSI-027 (1 mg/kg) or control (equal quantity of vehicle) groups; treatments are administered via the vena caudalis from day 7 to day 15.

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    References

    Purity: 99.40%

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    Keywords:

    OSI-027ASP7486OSI027OSI 027ASP 7486ASP-7486mTORAutophagyMammalian target of RapamycinInhibitorinhibitorinhibit

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    Product Name:
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    Cat. No.:
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