Dactolisib

SKU: orb1305985

Description

Dactolisib

Research Area

Cell Biology, Molecular Biology, Signal Transduction

Key Properties

• CAS Number: 915019-65-7
• MW: 469.54
• Purity: 99.71%
• Formula: C₃₀H₂₃N₅O
• SMILES: O=C1N(C=2C=3C(N=CC2N1C)=CC=C(C3)C4=CC5=C(N=C4)C=CC=C5)C6=CC=C(C(C#N)(C)C)C=C6
• Target: mTOR,PI3K,Autophagy,ATM/ATR
• Solubility: DMSO:1 mg/mL (2.13 mM);H2O:< 0.1 mg/mL (insoluble)

Bioactivity

• Target IC50:
  p110α-H1047R:4.6 nM|p110β:75 nM (cell free)|p110γ:5 nM (cell free)|p110α-E545K:5.7 nM|p110α:4 nM (cell free)|p110δ:7 nM (cell free)|mTOR (p70S6K):6 nM (cell free)
• In Vivo:
  I the absence of inhibitors the weight o the chamber, as well as levels o the endothelial cell marker Tie-2, were significantly increased in the presence of VEGF. Both effects were significantly inhibited in a dose-dependent manner whe the mice were treated with NVP-BEZ235 given p.o. twice a day at 20 mg/kg or once at 30 mg/kg, showin the specificity o the angiogenic response driven b the VEGF. NVP-BEZ235–treated adenomas (20 mg/kg) showed pronounced vacuolation o the cytoplasm when compared with PEG-treated animals. Vacuoles appeared even more prominent a the 30 and 45 mg/kg doses.
• In Vitro:
  Dactolisib (BEZ235) shows slightly lower activity agains the β paralogue IC50 75 nMol/L). NVP-BEZ235 (250 nMol/L) was able to reduce IGF-I-induced S473P-Akt levels belo the limit of detection, wherea the phosphorylation o the p85 binding site on IGF-IR (Y1316) was not altered. BEZ235 provoked a more profound effect with an IC50 value of 1.8 nMol/L and cytostasis was obtained at 10 nMol/L. Moreover, at a concentration of 100 nMol/L the BrdUrd uptake was less tha the one observed in starved, VEGF-untreated cells, indicative of cell death induction.
• Cell Research:
  The proliferation of BON1, QGP1, and αT3 cells after treatment was measured wit the WST-1 colorimetric assay. Cell proliferation in 3D spheroids was measured wit the CellTiter-Glo Cell Viability Assay according to the manufacturer's recommendations. Apoptosis was measured by assessin the activity of caspase-3/7 usin the Caspase-Glo 3/7 Assay Kit. BON1 cells and QGP1 cells were transfected with scrambled or anti-DEFB1 siRNA as above, and 24 hours later treated with NVP-BEZ235 or DMSO for an additional 24 hours. Caspase-3/7 activity was then assessed with a proluminescent caspase-3/7 substratee, which contain the tetrapeptide sequence DEVD. Luminescence was measured with a luminometer.
• Animal Research:
  Three doses of NVP-BEZ235 were tested in MENX rats: 20, 30, and 45 mg/kg. A the two higher doses caused a weight loss >10% after 10 days of treatment the dose of 20 mg/kg was used for further studies. For MRI studies, MENX-affected rats at 7 to 8 months of age (with sizeable adenomas but still in good general health) were treated for 14 days with NVP-BEZ235 (20 mg/kg) or placebo (PEG) administered daily per oral gavage the side effect o the drug we observed was mild diarrhea in the last days o the treatment (4/8 rats). Being this our first in vivo study of spontaneous rat pituitary adenomas, functional/molecular Changes in the tumors were considered more objective and measurable endpoints Primary endpoints) compared to the size and/or survival (secondary endpoints).

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Disclaimer: For research use only

Alternative Names

Dactolisib, BEZ 235, BEZ235, BEZ-235, Autophagy, ATM, ATR, Inhibitor, Mammalian target of Rapamycin, NVP-BEZ235, NVP-BEZ-235, NVP-BEZ 235, p110α, p110γ, p110δ, inhibit, mTOR (p70S6K), mTOR, PI3K, Phosphoinositide 3-kinase

Compound Identifiers

PubChem CID

11977753