Buparlisib-Hydrochloride-BKM120-Hydrochloride-DataSheet-生命科學(xué)試劑-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEBuparlisib HydrochlorideCat. No.: HY-15180CAS No.: 1312445-63-8Synonyms: BKM120 (Hydrochloride); NVP-BKM120 (Hydrochloride)分式: CHClFNO分量: 446.85作靶點(diǎn): PI3K作通路: PI3K/Akt/mTOR儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 month

2、s-20C 1 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 50 mg/mL (111.89 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液1 mM 2.2379 mL 11.1894 mL 22.3789 mL5 mM 0.4476 mL 2.2379 mL 4.4758 mL10 mM 0.2238 mL 1.1189 mL 2.2379 mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲備液，并請注意儲備液的保存式和期限。體內(nèi)實(shí)驗(yàn)請根據(jù)您的實(shí)驗(yàn)動物和給

3、藥式選擇適當(dāng)?shù)娜芙獍?，配制前請先配制澄清的儲備液，再依次添加助溶?為保證實(shí)驗(yàn)結(jié)果的可靠性，體內(nèi)實(shí)驗(yàn)的作液，建議您現(xiàn)現(xiàn)配，當(dāng)天使；澄清的儲備液可以根據(jù)儲存條件，適當(dāng)保存；以下溶劑前的百分 指該溶劑在您配制終溶液中的體積占)：1. 請依序添加每種溶劑： 0.5% CMC-Na/saline waterSolubility: 10 mg/mL (22.38 mM); Precipitated solution; Need ultrasonic2. 請依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (

4、5.59 mM); Clear solution1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE3. 請依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (5.59 mM); Clear solution4. 請依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (5.59 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 Buparlisib Hydrochloride (

5、BKM120 Hydrochloride)種 pan-class I PI3K 抑制劑，作于p110/p110/p110/p110，IC50 分別為 52 nM/166 nM/116 nM/262 nM。IC50 & Target p110 p110-H1047R p110-E545K p11052 nM (IC50) 58 nM (IC50) 99 nM (IC50) 116 nM (IC50)p110 p110 Vps34 mTOR166 nM (IC50) 262 nM (IC50) 2.4 M (IC50) 4.6 M (IC50)體外研究 Buparlisib (BKM120) ex

6、hibits 50-300 nM activity for class I PI3Ks, including the most common p110mutants. Additionally, NVP-BKM120 exhibits lower potency against class III and class IV PI3Ks, where 2, 5,5, and 25 M biochemical activity is observed for inhibition of VPS34, mTOR, DNAPK, and PI4K,respectively 1. Buparlisib

7、(BKM120) induces multiple myeloma (MM) cell apoptosis in both dose- and time-dependent manners. Buparlisib (BKM120) at concentrations 10 M induces significant apoptosis in alltested MM cell lines at 24 h (P50 varies among tested MM cells. At 24 h treatment, IC50 for ARP-1, ARK,and MM.1R is between 1

8、 and 10 M, while IC50 for MM.1S is 50 for U266 is between 10 and 100 M. Insummary, Buparlisib (BKM120) treatment results in MM cell growth inhibition and apoptosis in dose- andtime-dependent manners 2.體內(nèi)研究 In A2780 xenograft tumors, oral dosing of Buparlisib (BKM120) at 3, 10, 30, 60, and 100 mg/kg

9、results in adose dependent modulation of pAKTSer473. Partial inhibition of pAKTSer473 is observed at 3 and 10 mg/kg,and near complete inhibition is observed at doses of 30, 60, or 100 mg/kg, respectively. Inhibition of pAKT(normalized to total AKT) tracked well with both plasma and tumor drug exposu

10、re 1. Mice receivingBuparlisib (BKM120) (5 M per kg per day for 15 days) treatment has significantly smaller tumor burdens ascompare with control mice, which are measured as tumor volume (P 2.PROTOCOLCell Assay 1 A2780 cells are cultured in DMEM supplemented with 10% FBS. L-glutamine, sodium pyruvat

11、e, andantibiotics. Cells are plated in the same medium at a density of 1000 cells per well, 100 uL per well intoblack-walled-clear-bottom plates and incubated for 3-5 hours. Buparlisib (BKM120) supplied in DMSO (20mM) are diluted further into DMSO (7.5 uL of 20 mM NVP-BKM120 in 22.5 uL DMSO. Mix wel

12、l, transfer 10uL 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 addedto the cells in 96 well plates and incubated at 37C for 3 days and develo

13、ped using Cell Titer Glo. Inhibition of2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEcell proliferation is determined by luminescence read using Trilux 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice 2Administration 2 Six- to eight-week

14、-old female severe combined immunodeficiency (SCID) mice are used. SCID mice aresubcutaneously inoculated in the right flank with 1 million ARP-1 or MM.1S cells suspended in 50 Lphosphate-buffered saline (PBS). After palpable tumor developed (tumor diameter 5 mm), mice are treatedwith intraperitonea

15、l injection of DMSO/PBS or Buparlisib (BKM120) (5 M per kg per day) for 15 days. Tumorsizes are measured every 5 days, and blood samples are collected at the same period. Tumor burdens areevaluated by measuring tumor size and detecting circulating human kappa chain or lambda chain.MCE has not indepe

16、ndently confirmed the accuracy of these methods. They are for reference only.戶使本產(chǎn)品發(fā)表的科研獻(xiàn) Nature. 2018 Aug;560(7719):499-503. Nat Med. 2016 Jul;22(7):723-6. Cancer Discov. 2019 Jun. Cancer Discov. 2018 Mar;8(3):354-369. Sci Transl Med. 2018 Jul 18;10(450). pii: eaaq1093.See more customer validations

17、on HYPERLINK / www.MedChemEREFERENCES1. Burger MT, et al. Identification of NVP-BKM120 as a Potent, Selective, Orally Bioavailable Class I PI3 Kinase Inhibitor for TreatingCancer. ACS Med Chem Lett. 2011 Aug 26;2(10):774-9.2. Zheng Y, et al. Novel phosphatidylinositol 3-kinase inhibitor NVP-BKM120 induces apoptosis in myeloma cells and shows synergisticanti-myeloma activity w