NVP-BKM120 Hydrochloride |
カタログ番号GC14504
One-Click Copy Product Info
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クラスI PI3Kアイソフォームの阻害剤
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1312445-63-8
Sample solution is provided at 25 µL, 10mM.
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NVP-BKM120 is a selective PI3K inhibitor of p110α/β/δ/γ with IC50 of 52 nM/166 nM/116 nM/262 nM, respectively.
The intracellular phosphatidylinositol-3-kinase(PI3K) pathway regulates cellular functions incuding cell proliferation, growth, survival, apoptosis, protein synthesis, and glucose metabolism. NVP-BKM120, a biologic characterization of the 2-morpholino pyrimidine derivative, is a pan-PI3K inhibitor.
In vitro: NVP-BKM120 inhibits all four class I PI3K isoforms in biochemical assays with at least 50-fold selectivity against other protein kinases. NVP-BKM120 is also active against the most common somatic PI3Ka mutations but does not significantly inhibit the related class III (Vps34) and class IV (mTOR, DNA-PK) PI3K kinases. Consistent with its mechanism of action, NVP-BKM120 decreases the cellular p-Akt levels in mechanistic models and relevant tumor cell lines. In a panel of 353 cell lines test, NVP-BKM120 showed preferential inhibition of tumor cells with PIK3CA mutations, rather than either KRAS or PTEN mutant models [1].
In vivo: NVP-BKM120 shows dose-dependent in vivo pharmacodynamic activity as measured by significant inhibition of p-Akt and tumor growth inhibition in mechanistic xenograft models. In addition, NVP-BKM120 behaves synergistically when combined with either targeted agents such as MEK or HER2 inhibitors or with cytotoxic agents such as docetaxel or temozolomide [1].
Clinical trial: A phase I dose-escalation study investigated the maximum-tolerated dose (MTD), safety, preliminary activity, PK, and PD of BKM120. This study demonstrates feasibility and proof-of-concept of class I PI3K inhibition in cancer patients. BKM120 at the MTD of 100 mg d-1 is safe and well tolerated, with a good PK profile, clear evidence of target inhibition, and preliminary antitumor activity [2].
References:
[1] Maira SM, Pecchi S, Huang A, Burger M, Knapp M, Sterker D, Schnell C, Guthy D, Nagel T, Wiesmann M, Brachmann S, Fritsch C, Dorsch M, Chène P, Shoemaker K, De Pover A, Menezes D, Martiny-Baron G, Fabbro D, Wilson CJ, Schlegel R, Hofmann F, García-Echeverría C, Sellers WR, Voliva CF. Identification and characterization of NVP-BKM120, an orally available pan-class I PI3-kinase inhibitor. Mol Cancer Ther. 2012;11(2):317-28.
[2] Bendell JC, Rodon J, Burris HA, de Jonge M, Verweij J, Birle D, Demanse D, De Buck SS, Ru QC, Peters M, Goldbrunner M, Baselga J. Phase I, dose-escalation study of BKM120, an oral pan-Class I PI3K inhibitor, in patients with advanced solid tumors. J Clin Oncol. 2012;30(3):282-90.
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Cell experiment: |
A2780 cells are cultured in DMEM supplemented with 10% FBS. L-glutamine, sodium pyruvate, and antibiotics. Cells are plated in the same medium at a density of 1000 cells per well, 100 uL per well into black-walled-clear-bottom plates and incubated for 3-5 hours. Buparlisib (BKM120) supplied in DMSO (20 mM) are diluted further into DMSO (7.5 uL of 20 mM NVP-BKM120 in 22.5 uL DMSO. Mix well, transfer 10 uL to 20 uL DMSO, repeat until 9 concentrations have been made). The diluted Buparlisib (BKM120) solution (2 uL), is then added to cell medium (500 uL) cell medium. Equal volumes of this solution (100 uL) are added to the cells in 96 well plates and incubated at 37ºC for 3 days and developed using Cell Titer Glo. Inhibition of cell proliferation is determined by luminescence read using Trilux[1]. |
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Animal experiment: |
Mice[2]Six- to eight-week-old female severe combined immunodeficiency (SCID) mice are used. SCID mice are subcutaneously inoculated in the right flank with 1 million ARP-1 or MM.1S cells suspended in 50 μL phosphate-buffered saline (PBS). After palpable tumor developed (tumor diameter ≥5 mm), mice are treated with intraperitoneal injection of DMSO/PBS or Buparlisib (BKM120) (5 μM per kg per day) for 15 days. Tumor sizes are measured every 5 days, and blood samples are collected at the same period. Tumor burdens are evaluated by measuring tumor size and detecting circulating human kappa chain or lambda chain. |
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References: [1]. Burger MT, et al. Identification of NVP-BKM120 as a Potent, Selective, Orally Bioavailable Class I PI3 Kinase Inhibitor for Treating Cancer. ACS Med Chem Lett. 2011 Aug 26;2(10):774-9. |
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| Cas No. | 1312445-63-8 | SDF | |
| Chemical Name | 5-(2,6-dimorpholin-4-ylpyrimidin-4-yl)-4-(trifluoromethyl)pyridin-2-amine hydrochloride | ||
| Canonical SMILES | C1COCCN1C2=NC(=NC(=C2)C3=CN=C(C=C3C(F)(F)F)N)N4CCOCC4.Cl | ||
| Formula | C18H22ClF3N6O2 | M.Wt | 446.85 |
| 溶解度 | 20 mg/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 | 2.2379 mL | 11.1894 mL | 22.3789 mL |
| 5 mM | 447.6 μL | 2.2379 mL | 4.4758 mL |
| 10 mM | 223.8 μL | 1.1189 mL | 2.2379 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
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Working concentration: mg/ml;
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. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
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.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >99.50% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 30 reference(s) in Google Scholar.)