布帕尼西作用機(jī)制 - Medchemexpress - MCE中國(guó)

1、Product Data SheetBuparlisibCat. No.: HY-70063CAS No.: 944396-07-0分式: CHFNO分量: 410.39作靶點(diǎn): PI3K; Apoptosis作通路: PI3K/Akt/mTOR; Apoptosis儲(chǔ)存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 100 mg/mL (243.67 mM)* means soluble, but saturation unknown.SolventMass1 mg 5

2、mg 10 mgConcentration制備儲(chǔ)備液1 mM 2.4367 mL 12.1835 mL 24.3671 mL5 mM 0.4873 mL 2.4367 mL 4.8734 mL10 mM 0.2437 mL 1.2184 mL 2.4367 mL請(qǐng)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(chǔ)備液；旦配成溶液，請(qǐng)分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲(chǔ)備液的保存式和期限：-80C, 6 months; -20C, 1 month。-80C 儲(chǔ)存時(shí)，請(qǐng)?jiān)?6 個(gè)內(nèi)使，-20C 儲(chǔ)存時(shí)，請(qǐng)?jiān)?1 個(gè)內(nèi)使。體內(nèi)實(shí)驗(yàn)請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥式選擇適當(dāng)?shù)娜芙獍?。以下溶解案都?qǐng)先按照 I

3、n Vitro 式配制澄清的儲(chǔ)備液，再依次添加助溶劑：為保證實(shí)驗(yàn)結(jié)果的可靠性，澄 的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)的作液，建議您現(xiàn)現(xiàn)配，當(dāng)天使； 以下溶劑前顯的百分 指該溶劑在您配制終溶液中的體積占；如在配制過(guò)程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過(guò)加熱和/或超聲的式助溶1. 請(qǐng)依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (6.09 mM); Clear solution此案可獲得 2.5 mg/mL (6.09 mM，飽和度未知) 的澄清溶液。以 1 mL 作液為例，取 100 L 2

4、5.0 mg/mL 的澄 DMSO 儲(chǔ)備液加到 400 L PEG300 中，混合均勻；向上述體系中加50 L Tween-80，混合均勻；然后繼續(xù)加 450 L 理鹽定容 1 mL。2. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (6.09 mM); Clear solutionPage 1 of 2 www.MedChemE此案可獲得 2.5 mg/mL (6.09 mM，飽和度未知) 的澄清溶液。以 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄 DMSO 儲(chǔ)備液加到 900 L

5、 20% 的 SBE-CD 理鹽溶液中，混合均勻。3. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (6.09 mM); Clear solution此案可獲得 2.5 mg/mL (6.09 mM，飽和度未知) 的澄 溶液，此案不適于實(shí)驗(yàn)周 期在半個(gè)以上的實(shí)驗(yàn)。以 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄 DMSO 儲(chǔ)備液加到 900 L 油中，混合均勻。BIOLOGICAL ACTIVITY物活性 Buparlisib (BKM120; NVP-BKM120)種 pan-class I PI3K 抑制劑，

6、作于 p110/p110/p110/p110，IC50 分別為 52 nM/166 nM/116 nM/262 nM。IC & 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 (NVP-BKM120) exhibits 50-300 nM activity for class I PI3

7、Ks, including the most common p110 mutants.Additionally, NVP-BKM120 exhibits lower potency against class III and class IV PI3Ks, where 2, 5, 5, and 25 Mbiochemical activity is observed for inhibition of VPS34, mTOR, DNAPK, and PI4K, respectively1. Buparlisib (NVP-BKM120) induces multiple myeloma (MM

8、) cell apoptosis in both dose- and time-dependent manners. Buparlisib(NVP-BKM120) at concentrations 10 M induces significant apoptosis in all tested MM cell lines at 24 h (P0.05,compares with control). Therefore, 10 M Buparlisib (NVP-BKM120) and 24-h treatment are chose in in the followingexperiment

9、s if not stated otherwise. Buparlisib (NVP-BKM120) treatment results in a dose-dependent growthinhibition in all tested MM cell lines. Buparlisib (NVP-BKM120) IC50 varies among tested MM cells. At 24 h treatment,IC50 for ARP-1, ARK, and MM.1R is between 1 and 10 M, while IC50 for MM.1S is 1 M, and I

10、C50 for U266 isbetween 10 and 100 M. In summary, NVP-BKM120 treatment results in MM cell growth inhibition and apoptosis indose- and time-dependent manners2.體內(nèi)研究 In A2780 xenograft tumors, oral dosing of Buparlisib (NVP-BKM120) at 3, 10, 30, 60, and 100 mg/kg results in a dosedependent modulation of

11、 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 totalAKT) tracked well with both plasma and tumor drug exposure1. Mice receiving Buparlisib (NVP-BKM

12、120) (5 M perkg per day for 15 days) treatment has significantly smaller tumor burdens as compare with control mice, which aremeasured as tumor volume (P0.05) and level of circulating human kappa chain (P0.05). In addition, NVP-BKM120treatment significantly prolongs the survival of tumor-bearing mic

13、e (P0.05)2.PROTOCOLCell Assay 1 A2780 cells are cultured in DMEM supplemented with 10% FBS. L-glutamine, sodium pyruvate, and antibiotics. Cellsare plated in the same medium at a density of 1000 cells per well, 100 uL per well into black-walled-clear-bottomplates and incubated for 3-5 hours. Buparli

14、sib (NVP-BKM120) supplied in DMSO (20 mM) are diluted further intoDMSO (7.5 uL of 20 mM Buparlisib (NVP-BKM120) in 22.5 uL DMSO. Mix well, transfer 10 uL to 20 uL DMSO, repeatuntil 9 concentrations have been made). The diluted Buparlisib (NVP-BKM120) solution (2 uL), is then added to cellmedium (500

15、 uL) cell medium. Equal volumes of this solution (100 uL) are added to the cells in 96 well plates andPage 2 of 3 www.MedChemEincubated at 37C for 3 days and developed using Cell Titer Glo. Inhibition of cell proliferation is determined byluminescence read using Trilux1.MCE has not independently con

16、firmed the accuracy of these methods. They are for reference only.Animal Mice2Administration 2 Six- to eight-week-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 L phosphat

17、e-buffered saline (PBS). After palpable tumor developed (tumor diameter 5 mm), mice are treated with intraperitonealinjection of DMSO/PBS or Buparlisib (NVP-BKM120) (5 M per kg per day) for 15 days. Tumor sizes are measuredevery 5 days, and blood samples are collected at the same period. Tumor burde

18、ns are evaluated by measuring tumorsize and detecting circulating human kappa chain or lambda chain.MCE has not independently 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 Sep;9(

19、9):1306-1323. Cancer Discov. 2018 Mar;8(3):354-369. Sci Transl Med. 2018 Jul 18;10(450). pii: eaaq1093.See more customer validations on HYPERLINK www.MedChemE www.MedChemEREFERENCES1. Burger MT, et al. Identification of NVP-BKM120 as a Potent, Selective, Orally Bioavailable Class I PI3 Kinase Inhibitor for Treating Cancer. ACS Med ChemLett. 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 synergistic anti-myelomaactivity.