OSI-027

SKU: orb1300874

Description

OSI-027 (ASP4786) is a potent and selective dual mTORC1/mTORC2 inhibitor with IC50 values of 22 nM and 65 nM, respectively, demonstrating over 100-fold selectivity against related PI3K isoforms and DNA-PK. This tool compound has been utilized in preclinical research to investigate mTOR signaling in cancer models, both in vitro and in vivo, during its Phase 1 clinical development.

Research Area

Cell Biology, Molecular Biology, Signal Transduction

Key Properties

• CAS Number: 936890-98-1
• MW: 406.44
• Purity: 98.00% (May vary between batches)
• Formula: C₂₁H₂₂N₆O₃
• SMILES: COc1cccc2=C\C(N=c12)=c1/nc(C2CCC(CC2)C(O)=O)n2NC=NC(N)=c12
• Target: DNA-PK,Autophagy,PI3K,mTOR
• Solubility: Ethanol:< 1 mg/mL (insoluble or slightly soluble);DMSO:15 mg/mL (36.91 mM);H2O:< 1 mg/mL (insoluble or slightly soluble);10% DMSO+40% PEG300+5% Tween 80+45% Saline:2 mg/mL (4.92 mM)

Bioactivity

• Target IC50:
  PI3Kγ:0.42 μM|mTOR:4 nM|DNA-PK:1 μM|PI3Kα:1.3 μM|mTORC2:65 nM|mTORC1:22 nM
• In Vivo:
  In GEO colorectal xenograft, OSI-027 (65 mg/kg) inhibits both mTORC1 and mTORC2 effectors, including 4E-BP1, Akt, and S6 phosphorylation. Furthermore, mTORC1 and mTORC2 inhibition together by OSI-027 potently inhibits tumor growth more than mTORC1 inhibition by rapamycin.
• In Vitro:
  OSI-027 shows the selective and ATP competitive inhibition activities against mTORC1 and mTORC2 with IC50 of 22 nM and 65 nM, respectively. In addition, OSI-027 inhibits mTOR signaling of phospho-4E-BP1 with an IC50 of 1 μM in cell-based assays. OSI-027 exhibits anti-proliferative activities against several acute leukemia cell lines of myeloid/megakaryocytic origin in a dose-dependent manner, including U937, KG-1, KBM-3B, ML-1, HL-60, and MEG-01 cells. A recent study shows that inhibition of mTORC1/2 by OSI-027 effectively suppresses phosphorylation of Akt (S473) and cell proliferation in breast cancer cells.
• Cell Research:
  Inhibition of proliferation is measured using the Cell Titer Glo Assay , as noted in figure legends. To generate dose–response curves, cell lines are seeded at a density of 5,000 cells per well in a 96-well plate. After 24 hours of plating, cells are dosed with varying concentrations of either OSI-027 or rapamycin. The signal for Cell Titer Glo Assay is determined 72 hours after dosing and normalized to that of vehicle-treated controls. Inhibition of proliferation, relative to vehicle-treated controls, is expressed as a fraction of 1 and graphed using PRISM software. (Only for Reference)

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

DNA-PK, DNAPK, ASP 4786, ASP 7486, ASP-4786, ASP7486, ASP-7486, ASP4786, Autophagy, OSI 027, OSI027, OSI-027, mTOR, mTORC2, mTORC1, inhibit, Inhibitor, Mammalian target of Rapamycin, PI3Kγ

Compound Identifiers

PubChem CID

135398516