硼替佐米作用机制 - Medchemexpress - MCE中国

1、Product Data SheetBortezomibCat. No.: HY-10227CAS No.: 179324-69-7分式: CHBNO分量: 384.24作靶点: Proteasome; NF-B; Apoptosis; Autophagy作通路: Metabolic Enzyme/Protease; NF-B; Apoptosis; Autophagy储存式: 4C, protect from light* In solvent : -80C, 6 months; -20C, 1 month (protect from light)溶解性数据体外实验 DMSO : 83.3

2、mg/mL (216.79 mM)* means soluble, but saturation unknown.SolventMass1 mg 5 mg 10 mgConcentration制备储备液1 mM 2.6025 mL 13.0127 mL 26.0254 mL5 mM 0.5205 mL 2.6025 mL 5.2051 mL10 mM 0.2603 mL 1.3013 mL 2.6025 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；旦配成溶液，请分装保存，避免反复冻融造成的产品失效。储备液的保存式和期限：-80C, 6 months; -20C, 1 month

3、 (protect from light)。-80C 储存时，请在 6 个内使，-20C 储存时，请在 1 个内使。体内实验请根据您的实验动物和给药式选择适当的溶解案。以下溶解案都请先按照 In Vitro 式配制澄清的储备液，再依次添加助溶剂：为保证实验结果的可靠性，澄 的储备液可以根据储存条件，适当保存；体内实验的作液，建议您现现配，当天使； 以下溶剂前显的百分 指该溶剂在您配制终溶液中的体积占；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的式助溶1. 请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility

4、: 2.08 mg/mL (5.41 mM); Clear solution此案可获得 2.08 mg/mL (5.41 mM，饱和度未知) 的澄清溶液。以 1 mL 作液为例，取 100 L 20.8 mg/mL 的澄 DMSO 储备液加到 400 L PEG300 中，混合均匀；向上述体系中加50 L Tween-80，混合均匀；然后继续加 450 L 理盐定容 1 mL。2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.08 mg/mL (5.41 mM); Clear solution此案可获得 2.08 mg

5、/mL (5.41 mM，饱和度未知) 的澄清溶液。以 1 mL 作液为例，取 100 L 20.8 mg/mL 的澄 DMSO 储备液加到 900 L 20% 的 SBE-CD 理盐溶液中，混合Page 1 of 2 www.MedChemE均匀。3. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 2.08 mg/mL (5.41 mM); Clear solution此案可获得 2.08 mg/mL (5.41 mM，饱和度未知) 的澄 溶液，此案不适于实验周 期在半个以上的实验。以 1 mL 作液为例，取 100 L 20.8 mg/mL 的澄

6、DMSO 储备液加到 900 L 油中，混合均匀。BIOLOGICAL ACTIVITY物活性 Bortezomib (PS-341)种可逆性和选择性的蛋酶体 (proteasome) 抑制剂，通过靶向苏氨酸残基有效抑制 20S 蛋酶体 (Ki=0.6 nM)。Bortezomib 破坏细胞周 期、诱导细胞凋亡以及抑制核因 NF-B。Bortezomib 第种于体的治疗性蛋酶体抑制剂，具有抗癌活性。IC & Target Ki: 0.6 nM (20S proteasome)1体外研究 Bortezomib (PS-341) (100 nM; 8 hours) results in the a

7、ccumulation of cells in G2-M, with a corresponding decrease inthe number of cells in G11.Bortezomib (PS-341) (5-100 nM; 20 hours) induces apoptosis in mantle-cell lymphoma (MCL) cell lines3.Bortezomib (PS-341) (20 nM; 1-14 hours) induces Noxa up-regulation in both MCL cell lines3.The IC50 of Bortezo

8、mib (PS-341) is found to be 2.46 nM for 26S proteasome in the B16F10 cells4.Bortezomib (PS-341) suppresses several anti-apoptotic proteins (e.g., Bcl-XL, Bcl-2, and STAT-3)5.Cell Cycle Analysis1Cell Line: PC-3 cellsConcentration: 100 nMIncubation Time: 8 hoursResult: Resulted in the accumulation of

9、cells in G2-M, with a corresponding decrease in thenumber of cells in G1.Apoptosis Analysis3Cell Line: JVM-2, Granta-519, Jeko, REC-1 cells (MCL cell lines)Concentration: 5-100 nMIncubation Time: 20 hoursResult: The median LD50 for these MCL cell lines was 31 nM (range, 18.2-60.1 nM).Western Blot An

10、alysis3Cell Line: wtp53 (Granta-519), mutp53 (Jeko) cellsConcentration: 20 nMIncubation Time: 1, 2, 4, 6, 14 hoursResult: Noxa up-regulation was detected between 2 to 4 hours after bortezomib (PS-341).Page 2 of 3 www.MedChemE体内研究 Bortezomib (PS-341) (0.3-1 mg/kg; i.v.; once weekly for 4 weeks) inhib

11、its PC-3 Tumor Growth in Nude Mice1.Animal Model: Male nude mice (xenograft tumor model bearing PC-3 cells)1Dosage: 0.3, 1 mg/kgAdministration: Intravenous injection; once weekly for 4 weeksResult: Resulted in a significant decrease in tumor growth 60% at dose of 1 mg/kg.户使本产品发表的科研献 Cell. 2019 Jul 1

12、1;178(2):330-345.e22. Nat Commun. 2017 May 22;8:15398. Clin Cancer Res. 2019 Jun 15;25(12):3630-3642. Theranostics. 2019 Aug 14;9(21):6334-6353. Elife. 2018 Aug 1;7. pii: e38430.See more customer validations on HYPERLINK www.MedChemE www.MedChemEREFERENCES1. Adams J, et al. Proteasome inhibitors: a

13、novel class of potent and effective antitumor agents. Cancer Res. 1999 Jun 1;59(11):2615-22.2. Shahshahan MA, et al. Potential usage of proteasome inhibitor bortezomib (Velcade, PS-341) in the treatment of metastaticmelanoma: basic and clinicalaspects. Am J Cancer Res. 2011;1(7):913-24.3. Prez-Galn

14、P, et al. The proteasome inhibitor bortezomib induces apoptosis in mantle-cell lymphoma through generation of ROS and Noxa activationindependent of p53 status. Blood. 2006 Jan 1;107(1):257-64.4. Yerlikaya A, et al. Combined effects of the proteasome inhibitor bortezomib and Hsp70 inhibitors on the B

15、16F10 melanoma cell line. Mol Med Rep. 2010Mar-Apr;3(2):333-9.5. Mujtaba T, et al. Advances in the understanding of mechanisms and therapeutic use of bortezomib. Discov Med. 2011 Dec;12(67):471-80.6. Fernndez Y, et al. Chemical blockage of the proteasome inhibitory function of bortezomib: impact on tumor cell death. J Biol Chem. 2006 Jan13;281(2):11