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Dactolisib

Catalog No. T2235 CAS 915019-65-7

Synonyms: BEZ235, NVP-BEZ235

Dactolisib (BEZ235) is an orally bioavailable inhibitor of PI3K and mTOR (IC50s: 4 nM/5 nM/7 nM/75 nM, and 20.7 nM for p110α/p110γ/p110δ/p110β and mTOR).

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Dactolisib, CAS 915019-65-7

Pack Size	Availability	Price/USD
25 mg	In stock	$ 39.00
50 mg	In stock	$ 52.00
100 mg	In stock	$ 64.00
200 mg	In stock	$ 108.00

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Purity: 99.85%

Purity: 99.71%

Purity: 98.38%

Purity: 97.64%

Biological Description

Chemical Properties

Storage & Solubility Information

Description	Dactolisib (BEZ235) is an orally bioavailable inhibitor of PI3K and mTOR (IC50s: 4 nM/5 nM/7 nM/75 nM, and 20.7 nM for p110α/p110γ/p110δ/p110β and mTOR).
Targets&IC50	p110α:4 nM (cell free), p110γ:5 nM (cell free), mTOR (p70S6K):6 nM (cell free), p110δ:7 nM (cell free), p110β:75 nM (cell free)
In vitro	Dactolisib (BEZ235) shows slightly lower activity against the β paralogue (IC50: 75 nmol/L). NVP-BEZ235 (250 nmol/L) was able to reduce IGF-I-induced S473P-Akt levels below the limit of detection, whereas the phosphorylation of the p85 binding site on IGF-IR (Y1316) was not altered [1]. 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 than the one observed in starved, VEGF-untreated cells, indicative of cell death induction [2].
In vivo	In the absence of inhibitors, the weight of the chamber, as well as levels of the endothelial cell marker Tie-2, were significantly increased in the presence of VEGF. Both effects were significantly inhibited in a dose-dependent manner when the mice were treated with NVP-BEZ235 given p.o. twice a day at 20 mg/kg or once at 30 mg/kg, showing the specificity of the angiogenic response driven by the VEGF [2]. NVP-BEZ235–treated adenomas (20 mg/kg) showed pronounced vacuolation of the cytoplasm when compared with PEG-treated animals. Vacuoles appeared even more prominent at the 30 and 45 mg/kg doses [3].
Kinase Assay	PI3Kα, β, and δ proteins were composed of the iSH2 domain of p85 NH2-terminally fused to the full-length protein p110 protein, with the exception of α that also did not contain the last 20 amino acids. PI3Kγ was produced as full-length protein deleted for its first 144 amino acids. All constructs were fused to a COOH-terminal His tag for convenient purification and then cloned into the pBlue-Bac4.5 (for α, β, and δ isoforms) or pVL1393 (for γ isoform) plasmids. The different vectors were then cotransfected with BaculoGold WT genomic DNA using methods recommended by the vendor for production of the respective recombinant baculoviruses and proteins. Compounds were tested for their activity against PI3K using a Kinase-Glo assay. The kinase reaction was done in 384-well black plate. Each well was loaded with 50 nL of test items (in 90% DMSO) and 5 μL reaction buffer [10 mmol/L Tris-HCl (pH 7.5), 50 mmol/L NaCl, 3 mmol/L MgCl2, 1 mmol/L DTT, and 0.05% CHAPS] containing 10 μg/mL PI substrate (l-α-phosphatidylinositol; Avanti Polar Lipids; prepared in 3% octyl-glucoside) and the PI3K proteins (10, 25, 10, and 150 nmol/L of p110α, p110β, p110δ, and p110γ, respectively) were then added. The reaction was started by the addition of 5 μL of 1 μmol/L ATP prepared in the reaction buffer and ran for either 60 (for p110α, p110β, and p110δ) or 120 min (for p110γ) and subsequently terminated by the addition of 10 μL Kinase-Glo buffer. The plates were then read in a Synergy 2 reader for luminescence detection [1].
Cell Research	The proliferation of BON1, QGP1, and αT3 cells after treatment was measured with the WST-1 colorimetric assay. Cell proliferation in 3D spheroids was measured with the CellTiter-Glo Cell Viability Assay according to the manufacturer's recommendations. Apoptosis was measured by assessing the activity of caspase-3/7 using 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 substrate, which contains the tetrapeptide sequence DEVD. Luminescence was measured with a luminometer [3].
Animal Research	Three doses of NVP-BEZ235 were tested in MENX rats: 20, 30, and 45 mg/kg. As 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 of the drug we observed was mild diarrhea in the last days of 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) [3].

Synonyms	BEZ235, NVP-BEZ235
Molecular Weight	469.54
Formula	C30H23N5O
CAS No.	915019-65-7

Storage

Powder: -20°C for 3 years | In solvent: -80°C for 1 year

Solubility Information

DMSO: 5.2 mg/mL (11.07 mM), Sonification and heating are recommended.

H2O: < 0.1 mg/mL (insoluble)

References and Literature

1. Maira SM, et al. Identification and characterization of NVP-BEZ235, a new orally available dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor with potent in vivo antitumor activity. Mol Cancer Ther. 2008 Jul;7(7):1851-63. 2. Schnell CR, et al. Effects of the dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor NVP-BEZ235 on the tumor vasculature: implications for clinical imaging. Cancer Res. 2008 Aug 15;68(16):6598-607. 3. Lee M, et al. Targeting PI3K/mTOR Signaling Displays Potent Antitumor Efficacy against Nonfunctioning Pituitary Adenomas. Clin Cancer Res. 2015 Jul 15;21(14):3204-15.

Citations

1. Meng Y, Lv T, Zhang J, et al.Temporospatial inhibition of Erk signaling is required for lymphatic valve formation.Signal Transduction and Targeted Therapy.2023, 8(1): 342. 2. Yang N, Fan Z, Sun S, et al.Discovery of highly potent and selective KRASG12C degraders by VHL-recruiting PROTACs for the treatment of tumors with KRASG12C-Mutation.European Journal of Medicinal Chemistry.2023: 115857.

Related compound libraries

This product is contained In the following compound libraries：

Anti-Cancer Active Compound Library Anti-Cancer Clinical Compound Library Inhibitor Library Anti-Cancer Drug Library Drug Repurposing Compound Library Kinase Inhibitor Library Oxidation-Reduction Compound Library Anti-Viral Compound Library DNA Damage & Repair Compound Library Target-Focused Phenotypic Screening Library

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Keywords

Dactolisib 915019-65-7 Autophagy DNA Damage/DNA Repair PI3K/Akt/mTOR signaling PI3K ATM/ATR mTOR inhibit Phosphoinositide 3-kinase BEZ-235 Mammalian target of Rapamycin NVP-BEZ-235 Inhibitor BEZ 235 BEZ235 NVP-BEZ235 NVP-BEZ 235 inhibitor

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