1、AlpelisibCat. No.: HY-15244CAS No.: 1217486-61-7分式: CHFNOS分量: 441.47作靶点: PI3K作通路: PI3K/Akt/mTOR储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO : 100 mg/mL (226.52 mM)* “ means soluble, but saturation unknown.ConcentrationSolvent Mass 1 mg 5 mg 10 mg1 mM 2.2652 mL
2、 11.3258 mL 22.6516 mL5 mM 0.4530 mL 2.2652 mL 4.5303 mL制备储备液10 mM 0.2265 mL 1.1326 mL 2.2652 mL请根据产品在不同溶剂中的溶解度，选择合适的溶剂配制储备液体内实验 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (5.66 mM); Clear solution1. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (5.66 mM); Clear solu
3、tion2. 请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (5.66 mM); Clear solution3. BIOLOGICAL ACTIVITY物活性 Alpelisib (BYL-719) 是有效，选择性的 PI3K 抑制剂， IC50 为5 nM。IC IC504 nM). Alpelisib (NVP-BYL719) potently inhibits Akt phosphorylation in cells transformed with PI3K (IC50=7415
4、nM) and shows significant reduced inhibitory activity in PI3K or PI3K isoforms transformed cells (15-fold compared with PI3K)2. Alpelisib (NVP-BYL719) decreases cell proliferation by blocking cell cycle in G0/G1 phase with no outstanding effects on apoptosis cell death in HOS and MOS-J tumor cells.
5、BYL-719 inhibits cell migration and can thus be considered as a cytostatic drug for osteosarcoma. In murine preclinical models of osteosarcoma, Alpelisib (NVP-BYL719) significantly decreases tumor progression and tumor ectopic bone formation as shown by a decrease of Ki67+ cells and tumor vasculariz
6、ation. Alpelisib (NVP-BYL719) rapidly inhibits the levels of P-AKT and P-mTOR in all cell lines assessed, confirming the functional activity of Alpelisib (NVP-BYL719) on osteosarcoma cells. After 72 hr of treatment, Alpelisib (NVP-BYL719) significantly inhibits the cell growth of all osteosarcoma ce
7、ll lines tested in a dose-dependent manner with an IC50 ranging from 6 to 15 M and with the IC90 from 24 to 42 M at 72 hr3.体内研究 Alpelisib (BYL-719) displays excellent oral bioavailability in rats, mice and dogs and does not show any significant inhibition of the CYP450 enzymes1. Alpelisib (BYL-719)
8、inhibits tumor growth in pre-clinical murine models of osteosarcoma. C57Bl/6J with MOS-J tumors (n=6 per group) are randomized as controls (vehicle) or Alpelisib (BYL-719) (12.5 mg/kg or 50 mg/kg per day)3.PROTOCOLCell Assay 3 Two thousand tumor cells are seeded into 96-well plates and, the day afte
9、r, the cells are treated with Alpelisib (BYL-719) (1-50 M) for 72 hr. Cell growth/viability is determined using a colorimetric assay using sodium 31-(phenylaminocarbonyl)-3,4-tetrazolium-bis(4-methoxy-6-nitro-)benzene sulfonic acid hydrate (XTT Reagent Assay Kit). Absorbance is read at 490 nm. Cell
10、viability is also determined by trypan blue exclusion assay; viable and nonviable cells are counted manually after 24 and 48 hr of treatment3.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Administration 23Rats2 Tumor xenografts are grown subcut
11、aneously or orthotopically in nude mice or nude Rowett rats (Hsd: RH-Fox1rnu) by injection of 3106 to 110 7 cells or implantation of tumor fragments of approximately 50 mg. Tumor-bearing animals mice are treated with either vehicle control, Alpelisib (NVP-BYL719), or NVP-BKM120 (p.o., every day) at
12、the doses indicated. For efficacy studies, tumor-bearing animals are enrolled when subcutaneously implanted tumors reached about 200 mm3 and treated with Alpelisib (NVP-BYL719) at 50 mg/kg daily. The response is reported as percentage change in tumor volume at last day of treatment relative to day 0
13、 (start of treatment). Mice3 A 5-week-old male C57Bl/6J mice are anesthetized by inhalation of an isoflurane/air mixture (2%, 1 L/min) before intramuscular injection of 1106 mouse MOS-J osteosarcoma cells in close proximity to the tibia, leading to a rapidly growing tumor in soft tissue with seconda
14、ry contiguous bone invasion. Tumors appeare at the injection site 8 days later and lead to osteoblastic lesions reproducing the osteoblastic form of human osteosarcoma. Three groups (n=6 per group) of C57Bl/6J are assigned randomly to receive either placebo or Alpelisib (BYL719) (oral administration
15、, 12.5-50 mg/kg daily). The preventive treatment starts 1 day after tumor cells inoculation. Four groups of 6 C57Bl/6J are assigned randomly to receive either placebo (oral administration of methylcellulose 0.5% and intraperitoneal injection of water), Alpelisib (BYL719) (oral administration of 50 m
16、g/kg per day), ifosfamide (intraperitoneal injection of 30 mg/kg three times during the first week), or a combination of Alpelisib (BYL719) (50 mg/kg daily) and ifosfamide (30 mg/kg, three times during the first week).MCE has not independently confirmed the accuracy of these methods. They are for re
17、ference only.客户使本产品发表的科研献www.MedChemE2See more customer validations on www.MedChemEREFERENCES1. Furet P, et al. Discovery of NVP-BYL719 a potent and selective phosphatidylinositol-3 kinase alpha inhibitor selected for clinical evaluation. Bioorg Med Chem Lett. 2013 Jul 1;23(13):3741-8.2. Fritsch C,
18、et al. Characterization of the novel and specific PI3K inhibitor NVP-BYL719 and development of the patient stratification strategy for clinical trials. Mol Cancer Ther. 2014 May;13(5):1117-29.3. Gobin B, et al. BYL719, a new -specific PI3K inhibitor: single administration and in combination with con
19、ventional chemotherapy for the treatment of osteosarcoma. Int J Cancer. 2015 Feb 15;136(4):784-96.4. Venot Q, et al. Targeted therapy in patients with PIK3CA-related overgrowth syndrome. Nature. 2018 Jun;558(7711):540-546.5. Ding J, et al. Inhibition of BTF3 sensitizes luminal breast cancer cells to
20、 PI3K inhibition through the transcriptional regulation of ER. Cancer Lett. 2018 Oct 10;440-441:54-63.McePdfHeightCaution: Product has not been fully validated for medical applications. For research use only.Tel: 400-820-3792; 021-58955995 Fax: 021-53700325 E-mail: techMedChemEMaster of Small Molecu
21、les 您边的抑制剂师 Nature. 2018 Jun;558(7711):540-546. Science. 2017 Dec 1;358(6367). Sci Transl Med. 2018 Jul 18;10(450). pii: eaaq1093. Blood. 2019 Jan 3;133(1):70-80. Cell Syst. 2018 Dec.www.MedChemE3紋紋员等对差旅费报销进行审核把关，确保票据来源合法，内容真实完整、合规。对未经批准擅自出差、不按规定开支和报销差旅费的人员进行严肃处理。各单位应当自觉接受审计部门对出差活动及相关经费支出的审计监督。第三十九条
22、 学校财务处会同有关部门对各单位的差旅费管理和使用情况进行监督检查。主要内容包括：（一）单位差旅费审批制度是否健全，出差活动是否按规定履行审批手续；（二）差旅费开支范围和开支标准是否符合规定；（三）差旅费报销是否符合规定；（四）是否向其他单位转嫁差旅费；（五）差旅费管理和使用的其他情况。第四十条 出差人员不得向接待单位提出正常公务活动以外的要求，不得在出差期间接受违反规定用公款支付的宴请、游览和非工作需要的参观，不得接受礼品、礼金和土特产品等。9.开放经济的宏观经济学 资本净流出的含义及其主要影响因素 净出口与资本净流出的关系 储蓄与国内投资和资本净流出的关系 名义汇率和真实汇率的含义及名义汇
23、率与外国物价水平和国内物价水平的关系 基于可贷资金市场和外汇市场的开放经济模型中均衡汇率的决定 政策和事件对开放经济的影响 重点考核 开放经济模型中均衡汇率的决定及政策和事件 对开放经济的影响 五、有关说明 1.本大纲的执笔人：荣宪屏 审核人：高秀艳 批准人：米娟 2.本大纲依据国家教育部西方经济学教学大纲并结合沈阳大学培养目标和专业要求编写的。 六、本门课程主要概念的中英文对照表 生产率 Productivity 生活水平 Living Standard 通货膨胀 Inflation 经济周期 Business Cycle 国内生产 总值 Gross Domestic Product 国民生
24、产总值 Gross National Product 国内生产净值 Net Domestic Product 国民收入 National Income 个人收入 Personal Income 个人可支配收入 Personal Disposable Income 漀渀攀蜆蚓蓕氀甀爀愀猀椀搀漀渀攀牁舃蚓臕耀lurasidone-metabolite-14326-hydrochloride-coa-37184-medchemexpr鎂蛖氀甀爀愀猀椀搀漀渀攀洀攀琀愀戀漀氀椀琀攀栀礀搀爀漀挀栀氀漀爀椀搀攀搀愀琀愀猀栀攀攀琀洀攀搀挀栀攀洀攀砀瀀爀攀牁舃蚓臗耀lurasidone-metabolite-1
25、4326-hydrochloride-rp-hplc-37184-medchem鎂蛘氀甀爀愀猀椀搀漀渀攀洀攀琀愀戀漀氀椀琀攀栀礀搀爀漀挀栀氀漀爀椀搀攀猀搀猀洀攀搀挀栀攀洀攀砀瀀爀攀猀猀瀀搀昀牁舃蚓臙鬀lut01鎇蛙氀甀琀CEP-33779Cat. No.: HY-15343CAS No.: 1257704-57-6分式: CHNOS分量: 462.57作靶点: JAK作通路: Epigenetics; JAK/STAT Signaling; Stem Cell/Wnt储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1
26、 month溶解性数据体外实验 DMSO : 50 mg/mL (108.09 mM; Need ultrasonic)ConcentrationSolvent Mass 1 mg 5 mg 10 mg1 mM 2.1618 mL 10.8092 mL 21.6183 mL5 mM 0.4324 mL 2.1618 mL 4.3237 mL制备储备液10 mM 0.2162 mL 1.0809 mL 2.1618 mL请根据产品在不同溶剂中的溶解度，选择合适的溶剂配制储备液体内实验 请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% salineSol
27、ubility: 2.5 mg/mL (5.40 mM); Clear solution1. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (5.40 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (5.40 mM); Clear solution3. BIOLOGICAL ACTIVITY物活性 CEP-33779是个新颖的，选择性，有服活性的 JAK2抑制剂， IC50值为1.80.6 nM。IC
28、 oral dosing for 14 days at 30 mg/kg bid results in tumor stasis and partial regressions in 5/10 animals1. CEP-33779 administration results in an almost complete shrinkage of tumors in most animals; few remaining tumor nodules were small, poorly vascularized, and had a necrotic appearance. CEP-33779
29、 suppressed activation of NF-B in tumors2.PROTOCOLKinase Assay 1 The kinase activity of baculovirus-expressed human JAK1, JAK2, or JAK3 is measured. Each 96-well Costar high binding plate is coated with 100 L/well of 10 g/mL neutravidin in TBS at 37 C for 2 h, followed by 100 L/well of 1 g/mL 15-mer
30、 peptide substrate at 37 C for 1 h. The kinase assay mixture (total volume=100 L/well) consisting of 20 mM HEPES (pH 7.2), ATP (0.2 M ATP for JAK1 and JAK2 and 0.1 M ATP for JAK3), 1 mM MnCl2, 0.1% BSA, and CEP-33779 (diluted in DMSO, 2.5% DMSO final in assay) is added to the assay plate. Enzyme is
31、added and the reaction is allowed to proceed for 20 min at room temperature. Detection of the phosphorylated product is performed by adding 100 L/well of diluted Eu-N1 labeled PY100 antibody. Samples are incubated at RT for 1 h, followed by addition of 100 L enhancement solution. Plates are agitated
32、 for 10 min, and the fluorescence of the resulting solution is measured. IC50 values are determined1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Administration 1Mice: Nude mice bearing CWR22 xenografts are dosed orally with 55 mg/kg of CEP-33
33、779 or a vehicle (PEG400). At 2, 6, and 24 h after dosing animals (3/group) are sacrificed, tumors are excised and plasma samples are prepared. Tumor extracts are prepared using Triton-based extraction buffer supplemented with inhibitors of proteases and phosphatases. Equal amounts of extracts are r
34、esolved on SDS-PAGE gels and STAT3 phosphorylation and expression are analyzed by Western blot using specific antibodies1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.客户使本产品发表的科研献See more customer validations on www.MedChemEREFERENCES1. Dugan BJ, et
35、al. A selective, orally bioavailable 1,2,4-triazolo1,5-apyridine-based inhibitor of Janus kinase 2 for use in anticancer therapy: discovery of CEP-33779. J Med Chem. 2012 Jun 14;55(11):5243-54.2. Seavey MM, et al. Therapeutic efficacy of CEP-33779, a novel selective JAK2 inhibitor, in a mouse model
36、of colitis-induced colorectal cancer. Mol Cancer Ther. 2012 Apr;11(4):984-93.3. Tang SJ, et al. CEP-33779 antagonizes ATP-binding cassette subfamily B member 1 mediated multidrug resistance by inhibiting its transport function. Biochem Pharmacol. 2014 Sep 15;91(2):144-56.McePdfHeight Patent. US20180
37、263995A1.www.MedChemE2Caution: Product has not been fully validated for medical applications. For research use only.Tel: 400-820-3792; 021-58955995 Fax: 021-53700325 E-mail: techMedChemEMaster of Small Molecules 您边的抑制剂师www.MedChemE3ImatinibCat. No.: HY-15463CAS No.: 152459-95-5分式: CHNO分量: 493.6作靶点:
38、c-Kit; Bcr-Abl; PDGFR; Autophagy作通路: Protein Tyrosine Kinase/RTK; Autophagy储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO : 40 mg/mL (81.04 mM; Need ultrasonic and warming)ConcentrationSolvent Mass 1 mg 5 mg 10 mg1 mM 2.0259 mL 10.1297 mL 20.2593 mL5 mM 0.4052 m
39、L 2.0259 mL 4.0519 mL制备储备液10 mM 0.2026 mL 1.0130 mL 2.0259 mL请根据产品在不同溶剂中的溶解度，选择合适的溶剂配制储备液BIOLOGICAL ACTIVITY物活性 Imatinib (STI571) 是种酪氨酸激酶抑制剂，可抑制 c-Kit， Bcr-Abl 和 PDGFR。IC the medium is then exchanged for serum-free medium (negative control) or serum-free medium containing serial dilutions of Imatini
40、b. After 48 h (control cultures do not reach confluence), the number of metabolically active cells is determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and absorbance is measured in a Packard Spectra microplate reader at 540 nm. Growth inhibition is calculated. Ex
41、periments are done in triplicates4.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Administration 56Mice5 The 40 tumor-bearing SCID mice are randomly divided into four groups (10 mice per group): the PS-ASODN group (5 M, each mouse receives 0.2 m
42、L by intratumor injection once daily); Imatinib group (0.1 mg/g body weight); liposome negative control group (0.01 mL/g); and saline group (0.01 mL/g). The mice in each group receive the relevant treatment by intra-tumor injection once daily from day 7 to day 28 after implantation. After 28 d, the
43、mice are sacrificed, and tumor weight and longest and shortest diameters are measured by electronic scale and vernier caliper, respectively. Inhibition of tumor growth is calculated. Rats6 Adult female Wistar-Albino rats (220-240 g) are used. Twenty-one days after the first surgical procedure, the r
44、ats undergo a second laparotomy to evaluate the occurrence of endometriosis. Twenty-four rats have visually confirmed endometriotic implants and are randomized into three groups to receive Imatinib (25 mg/kg/day, p.o.), Anastrozole (0.004 mg/day, p.o.), or normal saline (0.1 mL, i.p.) for 14 days.MC
45、E has not independently confirmed the accuracy of these methods. They are for reference only.客户使本产品发表的科研献See more customer validations on www.MedChemEREFERENCES Sci Transl Med. 2018 Jul 18;10(450). pii: eaaq1093. Stem Cell Reports. 2017 Dec 12;9(6):1948-1960. Cancer Lett. 2019 Apr 10;447:105-114. J
46、Med Chem. 2019 May 2. J Med Chem. 2016 Sep 22;59(18):8456-72.www.MedChemE21. Heinrich MC, et al. Inhibition of c-kit receptor tyrosine kinase activity by STI 571, a selective tyrosine kinase inhibitor. Blood. 2000 Aug 1;96(3):925-32.2. Guida T, et al. Sorafenib inhibits imatinib-resistant KIT and platelet-derived growth factor receptor beta gatekeeper mutants. Clin Cancer Res. 2007 Jun 1
