| 名稱 | Bortezomib |
| 描述 | Bortezomib (LDP 341) is a 20S proteasome inhibitor (Ki=0.6 nM) that is reversible and selective. Bortezomib has antitumor activity and inhibits NF-κB, which can disrupt the cell cycle and induce apoptosis. |
| 細(xì)胞實(shí)驗(yàn) | PC-3 cells were treated with different doses of PS-341 for different periods of time. The cells were washed with PBS, harvested, and fixed in suspension with 3.7% formaldehyde in the neutral buffer for 10 min at room temperature. The cells were centrifuged, and the cell pellet was resuspended in 0.5 ml of 80% ethanol. The cell suspension (25–50 μl) was then placed onto a microscope slide precoated with poly-l-lysine and air-dried. The slides were washed four times with 0.1% Triton X-100 in PBS. The slide was incubated with the DNA stain Hoechst 33342 (Molecular Probes; 1.0 μg/ml in PBS with 0.1% Triton-X-100) for 1.0 min. The slides were rinsed in PBS and mounted with 70% glycerol containing 25 mg/ml 1,4-diazabicyclo[2.2.2]octane. Nuclear staining was visualized using a fluorescent microscope [1]. |
| 激酶實(shí)驗(yàn) | Inhibitors were synthesized and purified according to the procedures described in Adams et al.The inhibition constant (Ki) for each inhibitor was measured according to the method of Stein et al.using a fluorometric assay,monitoring peptide substrate cleavage of Z-Leu-Leu-Val-Tyr-amino methyl coumarin (Z = carbobenzyloxy) by the 20S proteasome [1]. |
| 動(dòng)物實(shí)驗(yàn) | Mice were inoculated s.c. into the right flank with 3 × 10^7 MM cells in 100 μl of RPMI 1640, together with 100 μl of Matrigel basement membrane matrix. When tumor was measurable, mice were assigned into four treatment groups receiving PS-341 or into a control group. Treatment with PS-341 was given i.v. twice weekly via tail vein at 0.05, 0.1, 0.5, and 1.0 mg/kg for 4 weeks. Subsequently, it was administered once weekly. The control group received the vehicle alone (0.9% sodium chloride) at the same schedule. Caliper measurements of the longest perpendicular tumor diameters were performed every alternate day to estimate the tumor volume, using the following formula: 4π/3 × (width/2)^2 × (length/2), representing the three-dimensional volume of an ellipse. Animals were sacrificed when their tumors reached 2 cm or when the mice became moribund. Survival was evaluated from the first day of treatment until death [4]. |
| 體外活性 | 方法：人舌鱗癌細(xì)胞 SCC-15 和 CAL-27、人咽鱗癌細(xì)胞 FaDu、人唾液腺癌細(xì)胞 A-253 和 SALTO-5 用 Bortezomib (6.25-100 nM) 處理 24-72 h，使用 SRB 方法檢測(cè)細(xì)胞生長(zhǎng)抑制情況。
結(jié)果：Bortezomib 對(duì)五種腫瘤細(xì)胞增殖的影響是劑量和時(shí)間依賴性的。SCC-15 是對(duì) Bortezomib 作用最敏感的細(xì)胞。[1]
方法：人小細(xì)胞肺癌細(xì)胞 NCI-H69 和 NCI-H2171 用 Bortezomib (0.05 μM; 0.5 μM) 處理 48 h，使用 Flow Cytometry 方法檢測(cè)細(xì)胞周期和細(xì)胞凋亡情況。
結(jié)果：Bortezomib 引起 G2-M 過渡狀態(tài)下的細(xì)胞周期停滯，G2 期細(xì)胞增加，S 期細(xì)胞減少。Bortezomib 誘導(dǎo)腫瘤細(xì)胞凋亡。[2]
方法：人大細(xì)胞肺癌細(xì)胞 H460 用 Bortezomib (0.01-10 μM) 孵育 3-48 h，使用 Western Blot 方法檢測(cè)靶點(diǎn)蛋白表達(dá)水平。
結(jié)果：Bortezomib 處理導(dǎo)致 Bcl-2 蛋白的濃度依賴性磷酸化。從 12 h 開始，觀察到可辨別的 Bcl-2 切割產(chǎn)物，Bcl-2 磷酸化先于 Bcl-2 切割至少 9 h。[3] |
| 體內(nèi)活性 | 方法：為檢測(cè)體內(nèi)抗腫瘤活性，將 Bortezomib (0.3 mg/kg) 腹腔注射給攜帶原發(fā)性滲出性淋巴瘤 (PEL) UM-PEL-1 的 NOD/SCID 小鼠，每天一次，持續(xù)三周。
結(jié)果：Bortezomib 誘導(dǎo) PEL 緩解，并延長(zhǎng)淋巴瘤滲出小鼠的總生存期。Bortezomib 下調(diào)細(xì)胞周期進(jìn)程、DNA 復(fù)制和 Myc 靶基因。[4]
方法：為研究 Bortezomib 對(duì)腎纖維化的影響，將 Bortezomib (0.5 mg/kg) 腹腔注射給馬兜鈴酸I (AA)誘導(dǎo)的纖維化 C57BL/6J 小鼠模型，每周兩次，持續(xù)十周。
結(jié)果：Bortezomib 治療顯著減輕了 AA 誘導(dǎo)的腎功能障礙和蛋白尿，降低了腎纖維化相關(guān)蛋白和腎損傷標(biāo)志物的表達(dá)，如 αSMA、Kim1 和 Ngal，并在組織病理學(xué)水平上預(yù)防了腎纖維化。[5] |
| 存儲(chǔ)條件 | keep away from direct sunlight | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| 溶解度 | 10% DMSO+40% PEG300+5% Tween 80+45% Saline : 7.1 mg/mL (18.48 mM), Please add co-solvents sequentially, clarifying the solution as much as possible before adding the next one. Dissolve by heating and/or sonication if necessary. Working solution is recommended to be prepared and used immediately.
H2O : Insoluble
Ethanol : 20.83 mg/ml (54.21 mM), Sonication is recommended.
DMSO : 71 mg/mL (184.8 mM)
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| 關(guān)鍵字 | Nuclear factor-kappaB | Inhibitor | LDP-341 | Nuclear factor-κB | Apoptosis | LDP341 | PS 341 | PS341 | Bortezomib | Autophagy | Proteasome | MG341 | PS-341 | inhibit | NF-κB | NSC-681239 | NSC681239 | MG-341 |
| 相關(guān)產(chǎn)品 | Guanidine hydrochloride | Naringin | Valproic Acid | L-Glutamic acid | Gefitinib | Diallyl disulfide | Hydroxychloroquine | Dextran sulfate sodium salt (MW 4500-5500) | Stavudine | L-Ascorbic acid | Paeonol | Sodium 4-phenylbutyrate |
| 相關(guān)庫(kù) | 抑制劑庫(kù) | 抗癌上市藥物庫(kù) | 抗衰老化合物庫(kù) | FDA 上市藥物庫(kù) | 抗癌臨床化合物庫(kù) | 抗癌藥物庫(kù) |