| 名稱 | SHP099 hydrochloride |
| 描述 | SHP099 hydrochloride is a potent, selective, orally bioavailable SHP2 inhibitor with IC50 of 70 nM, which inhibits ERK1/2 activation in cancer cells. [2] |
| 細胞實驗 | Cells are plated onto 96-well plates in 100 μL medium. SHP099 with various concentrations (1.25, 2.5, 5, 10, 20 μM) are added 24 h after cell plating. At day 5, 50 μL Celltiter-Glo reagent is added, and the luminescent signal is determined[1]. |
| 激酶實驗 | The inhibition of SHP2 from the tested compounds (SHP099) concentrations varying from 0.003-100 μM is monitored using an assay in which 0.5 nM of SHP2 is incubated with of 0.5 μM of peptide IRS1_pY1172(dPEG8)pY1222. After 30-60 minutes incubation at the surrogate substrate, DiFMUP is added to the reaction and incubated at 25 °C for 30 minutes. The reaction is then quenched by the addition of 5 μL of a 160 μM solution of bpV(Phen). The fluorescence signal is monitored using a microplate reader using excitation and emission wavelengths of 340 nm and 450 nm, respectively[1]. |
| 體外活性 | 方法：不同濃度的SHP099（5,10,15,20,25,30,40,50μM）處理1周后，觀察SMSCs的細胞活力。
結(jié)果：SHP099在濃度大于25μM的時候抑制SMSCs的細胞活力。[2] |
| 體內(nèi)活性 | 方法：用SHP0999(1,3,10mg/kg)處理了咪喹莫特 （IMQ）誘導(dǎo)的小鼠銀屑病模型,觀察SHP099對IMQ誘導(dǎo)的小鼠模型中的銀屑病樣表型的影響。
結(jié)果：SHP099顯著抑制IMQ誘導(dǎo)的腫脹、表皮棘皮棘皮、角質(zhì)形成細胞增殖和真皮炎癥細胞浸潤，不影響正常小鼠的皮膚狀況；SHP099 也顯著降低了小鼠模型中血清 IL-23 和 IL-17A 水平。[1]
方法：評估了 SHP099 在 400 μL 體積中以 100 mg/kg 口服單劑量 SHP099 后在 C57BL/6J 小鼠中穿過 BBB 的能力。
結(jié)果：口服強飼后早期血漿和腦組織中SHP099濃度較高，在口服強飼后24 h，腦組織中SHP099的水平保持在可觀的水平。[2]
方法：CT-26 和 MC-38 細胞皮下接種到 BALB/c 小鼠中建立小鼠腫瘤模型，小鼠腫瘤模型使用SHP099鹽酸鹽（5mg/kg/kg/d，腹腔注射），觀察SHP099鹽酸鹽第腫瘤的影響。
結(jié)果：SHP099治療的腫瘤體積和重量均顯著降低。[3] |
| 存儲條件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| 溶解度 | Methanol : 15 mg/mL (38.59 mM), Sonication is recommended.
DMSO : 55 mg/mL (141.49 mM), Sonication and heating are recommended.
H2O : 10 mg/mL (25.73 mM), Sonication is recommended.
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| 關(guān)鍵字 | SHP-099 | SHP099 Hydrochloride | SHP 099 | SHP099 hydrochloride | Inhibitor | SHP 099 Hydrochloride | Phosphatase | inhibit | SHP-099 Hydrochloride | SHP-099 hydrochloride | SHP099 |
| 相關(guān)產(chǎn)品 | Sodium orthovanadate | Stearic acid | Tartaric acid disodium dihydrate | PTP1B-IN-22 | Cyclosporine | Cis-5-Norbornene-exo-2,3-dicarboxylic Anhydride | L-Ascorbic acid 2-phosphate magnesium | CaMKP Inhibitor | Idoxuridine | β-Glycerophosphate disodium salt pentahydrate | Tetramisole hydrochloride | Trimyristin |
| 相關(guān)庫 | 抑制劑庫 | 抗癌活性化合物庫 | 經(jīng)典已知活性庫 | 抗癌化合物庫 | 已知活性化合物庫 | 磷酸酶抑制劑化合物庫 | 高選擇性抑制劑庫 | 臨床前化合物庫 | 口服活性化合物庫 | 表型篩選靶點鑒定庫 |