| 名稱 | Vemurafenib |
| 描述 | Vemurafenib (RG7204) is a B-RAF inhibitor that inhibits RAFV600E and c-RAF-1 (IC50=31/48 nM) selectively and potently. Vemurafenib exhibits antitumor activity and is used for the treatment of BRAF V600E mutation-positive melanoma. |
| 細胞實驗 | Cellular proliferation was evaluated by MTT assay. Briefly, cells were plated in 96-well microtiter plates at a density of 1,000 to 5,000 cells per well in a volume of 180 μL. For the assay, RG7204 was prepared at 10 times the final assay concentration in media containing 1% DMSO. Twenty-four hours after cell plating, 20 μL of the appropriate dilution were added to plates in duplicate. The plates were assayed for proliferation 6 days after the cells were plated according to the procedure originally described by Mosmann [2]. |
| 激酶實驗 | Expression and purification of B-RAF, structure determination, and protein kinase activity measurements were carried out as previously described. To obtain co-crystals of B-RAFV600E with PLX4032, the protein solution was initially mixed with the compound dissolved in DMSO at a final compound concentration of 1 mM. This complex was co-crystallized by a sitting drop vapor diffusion experiment in which equal volumes of complex (at 10 mg/ml concentration) and reservoir solution (100mM BisTris at pH 6.0, 12.5% 2,5-hexanediol, and 12% PEG3350) were mixed and allowed to equilibrate against the reservoir at 4°C. The crystal was soaked in cryosolvent, followed by flash-freezing in liquid nitrogen. The data were collected at Beamline ALS831 with the wavelength of 1.11?. The Ramachandran plot from the refined structure shows that 94%, 5.6% and 0.4% residues are in the most favored, additional allowed and generously allowed regions, respectively. A summary of the crystallography statistics is included in Supplementary Table 3. COLO205 tumor xenograft studies (Molecular Imaging Research, Ann Arbor, MI) were carried out as previously described either using a conventional formulation (5%DMSO, 1% methylcellulose) or using the MBP formulation [1]. |
| 動物實驗 | All animal procedures were approved by the Ethical Commission of the Institute for Cancer Research and Treatment and by the Italian Ministry of Health. WiDr cells were injected subcutaneously into the right posterior flanks of 7-week-old immunodeficient NODSCID female mice (6 mice per group). Tumour formation was monitored twice a week, and tumour volume based on caliper measurements was calculated by the modified ellipsoidal formula: tumour volume = 1/2 length × width. When tumours reached a volume of approximately 200–250 mm^3, mice were randomly assigned to treatment with vehicle or drug(s) [3]. |
| 體外活性 | 方法：黑色素瘤細胞 A375 和 SK-Mel-28 用 Vemurafenib (0-8 μM) 處理 48 h，使用 CCK-8 assay 檢測細胞活力。
結果：Vemurafenib 劑量依賴性抑制 A375 和 SK-Mel-28 細胞增殖，IC50 分別為 0.8 μM 和 1.8 μM。[1]
方法：表達 BRAF V600E 的黑色素瘤細胞系 Colo829 和 LOX 用 Vemurafenib (0.05-30 μmol/L) 處理 2 h，使用 Western Blot 方法檢測靶點蛋白表達水平。
結果：Vemurafenib 抑制了 Colo829 和 LOX 細胞中 MEK 和 ERK 的磷酸化。[2] |
| 體內(nèi)活性 | 方法：為檢測體內(nèi)抗腫瘤活性，將 Vemurafenib (12.5-75 mg/kg，suspended in an aqueous vehicle containing 2% Klucel LF and adjusted to pH 4 with dilute HCl.) 口服給藥給攜帶黑色素瘤 LOX 的 Athymic nude 小鼠，每天兩次，持續(xù) 11-13 天。
結果：Vemurafenib 顯著抑制腫瘤生長并誘導腫瘤消退。[2]
方法：為檢測體內(nèi)抗腫瘤活性，將 Vemurafenib (60 mg/kg) 口服給藥給攜帶黑色素瘤 Colo-205 的 athymic mice 小鼠，每天兩次，持續(xù)十四天。
結果：Vemurafenib 有效抑制 Colo-205 異種移植小鼠模型中的腫瘤生長。[3] |
| 存儲條件 | Keep away from direct sunlight,Store at low temperature,Keep away from moisture
Powder: -20°C for 3 years | In solvent: -80°C for 1 year
Shipping with blue ice/Shipping at ambient temperature. |
| 溶解度 | Ethanol : < 1 mg/mL (insoluble or slightly soluble)
10% DMSO+40% PEG300+5% Tween 80+45% Saline : 9 mg/mL (18.37 mM), Suspension.
H2O : < 1 mg/mL (insoluble or slightly soluble)
DMSO : 99 mg/mL (202.07 mM), Sonication is recommended.
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| 關鍵字 | Vemurafenib | SRMS | RO-5185426 | RO 5185426 | RG-7204 | RG 7204 | Raf kinases | Raf | PLX-4032 | PLX 4032 | MAP4K5 (KHS1) | Inhibitor | inhibit | FGR | C-Raf | B-Raf (V600E) | B-Raf | Autophagy | ACK1 | 1029872-54-5 |
| 相關產(chǎn)品 | Guanidine hydrochloride | Naringin | Enzalutamide | Aceglutamide | Alginic acid | Cysteamine hydrochloride | Hemin | Hydroxychloroquine | Sildenafil citrate | Stavudine | Tamoxifen | Paeonol |
| 相關庫 | 腫瘤免疫治療小分子化合物庫 | 抗癌活性化合物庫 | 經(jīng)典已知活性庫 | 已知活性化合物庫 | EMA 上市藥物庫 | 高選擇性抑制劑庫 | 抗衰老化合物庫 | FDA 上市藥物庫 | 免疫/炎癥分子化合物庫 | 藥物功能重定位化合物庫 | 酪氨酸激酶分子庫 | 抗癌臨床化合物庫 |