BEZ235 (NVP-BEZ235) (Synonyms: Dactolisib) |
| Catalog No.GC10060 |
NVP-BEZ235 is a novel therapeutic agent that targets 2 molecules in thePI3K/Akt/mTOR (phosphatidylinositol 3-kinase) pathway, PI3K and mTOR.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 915019-65-7
Sample solution is provided at 25 µL, 10mM.
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NVP-BEZ235 is a novel therapeutic agent that targets 2 molecules in thePI3K/Akt/mTOR (phosphatidylinositol 3-kinase) pathway, PI3K and mTOR. It is an ATP-competitive pan-class I PI3K inhibitor that is effective against p110α with hotspot mutations, and likewise inhibits both mammalian target of rapamycin complex 1 (mTORC1) and mTORC2 [1]. NVP-BEZ235 antagonizes the PI3K/mTOR signaling pathway and induces cell-cycle arrest, autophagy, and downregulation of vascular endothelial growth factor in glioma cells. NVP-BEZ235 is also an effective radiosensitizer that inhibits ataxia telangiectasia mutated (ATM) and DNA-PK catalytic subunits (DNA-PKcs), arrests cell cycle, and induces apoptosis [2].
NVP-BEZ235 treated colorectal cancer (CRC) cell lines resulted in transient PI3K blockade, sustained decreases in mTORC1/mTORC2 signaling, and a corresponding decrease in cell viability (IC50 = 9.0-14.3 nM) [3]. All cell lines with PI3K-activating mutations or Pten deletions (A2780, IGROV1, MOVCAR18, OAW42, and SKOV3) were highly sensitive to NVP-BEZ235 (IC50 range 26-70 nM). In contrast, HEYC2, OV167, OV207, and OVCAR5 cells, that lack PI3K-activating mutations or Pten deletions, had an IC50 ≥ 100 nM (IC50 range 100-210 nM) for NVP-BEZ235. Overall, a statistically significant difference between the average NVP-BEZ235 IC50 for cell lines with PI3K mutations or Pten deletions (IC50 = 48.5 ± 8.1 nM) compared to cell lines that lack these mutations (IC50 = 95.9 ± 18.4 nM) [1].
Mouse model of Alzheimer's disease (AD) that expresses a mutant amyloid-β precursor protein (T41 mice) to investigate the effects of NVP-BEZ235. Ten-months-old T41 animals were treated for 14 days with NVP-BEZ235 or vehicle via oral gavage and then submitted to social memory, open field and contextual conditioned fear tests. Hippocampal slices were prepared and Aβ1-42 content, NeuN, Iba-1, CD68 and GFAP were evaluated. Tissues were further processed to evaluate cytokines levels through cytometric bead array. The treatment with NVP-BEZ235 (5 mg/kg) reduced social memory impairment in T41 mice. The drug reduced the CD68/Iba-1 ratio in CA3 region of hippocampus. NVP-BEZ235 diminished IL-10 levels in T41 mice [4].
References:
[1]. C. Santiskulvong, G.E. Konecny, M. Fekete, et al. Dual targeting of phosphoinositide 3-kinase and mammalian target of rapamycin using NVP-BEZ235 as a novel therapeutic approach in human ovarian carcinoma. Clin. Cancer Res., 17 (2011), pp. 2373-2384
[2]: Wang WJ, Long LM, Yang N, et al. NVP-BEZ235, a novel dual PI3K/mTOR inhibitor, enhances the radiosensitivity of human glioma stem cells in vitro. Acta Pharmacol Sin. 2013;34:681-690.
[3]. J. Roper, M.P. Richardson, W.V. Wang, L.G. Richard, W. Chen, E.M. Coffee, et al. The dual PI3K/mTOR inhibitor NVP-BEZ235 induces tumor regression in a genetically engineered mouse model of PIK3CA wild-type colorectal cancer. PLoS ONE, 6 (2011), p. e25132
[4]. P.M.Q. Bellozi, G.F. Gomes, L.R. de Oliveira, et al. NVP-BEZ235 (Dactolisib) has protective effects in a transgenic mouse model of Alzheimer's disease. Frontiers in Pharmacology, 10 (2019), p. 1345
| Cell experiment [1]: | |
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Cell lines |
Glioma stem cells |
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Preparation Method |
NVP-BEZ235 was dissolved in DMSO to obtain a stock concentration of 10 mmol/L, which was aliquoted and stored at -20 °C and diluted to the desired final concentration in DMEM/F12 at the time of use. The GSC cells were treated with various concentrations of NVP-BEZ235 for 24, 48, or 72 h. |
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Reaction Conditions |
10,20,40,80,160,320µM for 24, 48, or 72 h |
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Applications |
NVP-BEZ235 treatment significantly increased radiation sensitivity in GSCs, and the inhibition of autophagy by 3-MA blocked NVP-BEZ235-mediated radiosensitization. |
| Animal experiment [2]: | |
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Animal models |
male transgenic Tg (Thy1-APPSweLon) 41Ema (T41) mice and their wild-type (WT) littermates. |
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Preparation Method |
Animals were treated by oral gavage with 5 or 25 mg/kg of NVP-BEZ235, diluted in 1-metyl 2-pirrolidone 10% in PEG 300, or vehicle, once a day for 14 days. According to the genotype (WT or T41) and the treatment (NVP-BEZ235 or vehicle), the animals were divided into five groups: WT + Vehicle, WT + NVP-BEZ235 25 mg/kg (WT + BEZ 25), T41 + Vehicle, T41 + NVP-BEZ235 5 mg/kg (T41 + BEZ 5), and T41 + NVP-BEZ235 25 mg/kg (T41 + BEZ 25). |
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Dosage form |
5 or 25 mg/kg, oral |
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Applications |
BEZ 5 mg/kg significantly reversed this memory impairment in T41 mice. Memory loss is the main sign of Alzheimer's disease (AD) |
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References: [1]: Wang WJ, Long LM, Yang N, et al. NVP-BEZ235, a novel dual PI3K/mTOR inhibitor, enhances the radiosensitivity of human glioma stem cells in vitro. Acta Pharmacol Sin. 2013;34:681-690. |
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| Cas No. | 915019-65-7 | SDF | |
| Synonyms | Dactolisib | ||
| Chemical Name | 2-methyl-2-[4-(3-methyl-2-oxo-8-quinolin-3-ylimidazo[4,5-c]quinolin-1-yl)phenyl]propanenitrile | ||
| Canonical SMILES | CC(C)(C#N)C1=CC=C(C=C1)N2C3=C4C=C(C=CC4=NC=C3N(C2=O)C)C5=CC6=CC=CC=C6N=C5 | ||
| Formula | C30H23N5O | M.Wt | 469.55 |
| Solubility | ≥ 7.8mg/mL in DMSO | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.1297 mL | 10.6485 mL | 21.297 mL |
| 5 mM | 425.9 μL | 2.1297 mL | 4.2594 mL |
| 10 mM | 213 μL | 1.0648 mL | 2.1297 mL |
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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
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Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
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Quality Control & SDS
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- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 30 reference(s) in Google Scholar.)
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