| 名稱(chēng) | 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(xì)胞實(shí)驗(yàn) | 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(shí)驗(yàn) | 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(xì)胞活力。
結(jié)果：SHP099在濃度大于25μM的時(shí)候抑制SMSCs的細(xì)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(duì)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(xì)胞增殖和真皮炎癥細(xì)胞浸潤(rùn)，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(píng)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(guò) BBB 的能力。
結(jié)果：口服強(qiáng)飼后早期血漿和腦組織中SHP099濃度較高，在口服強(qiáng)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(xì)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(chǔ)條件 | 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 | 10% DMSO+90% Saline : 3.2 mg/mL (8.23 mM), Solution.
10% DMSO+40% PEG300+5% Tween-80+45% Saline : 2.5 mg/mL (6.43 mM), Sonication is recommended.
Methanol : 15 mg/mL (38.59 mM), Sonication is recommended.
DMSO : 32 mg/mL (82.32 mM), Sonication and heating are recommended.
H2O : 10 mg/mL (25.73 mM), Sonication is recommended.
|
| 關(guān)鍵字 | SHP-2 | SHP-099 Hydrochloride | SHP099 Hydrochloride | SHP-099 | SHP099 | SHP 099 Hydrochloride | SHP 099 | Phosphatase | Inhibitor | inhibit |
| 相關(guān)產(chǎn)品 | Hexane-1,6-diol | Cyclosporin A | Sodium orthovanadate | Stearic acid | Tartaric acid disodium dihydrate | Cyclosporine | L-Ascorbic acid 2-phosphate magnesium | β-Glycerophosphate disodium salt hydrate | CaMKP Inhibitor | Idoxuridine | L-Ascorbic acid 2-phosphate | β-Glycerophosphate disodium salt pentahydrate |
| 相關(guān)庫(kù) | 抑制劑庫(kù) | 脂代謝化合物庫(kù) | 抗癌活性化合物庫(kù) | 經(jīng)典已知活性庫(kù) | 抗癌化合物庫(kù) | 已知活性化合物庫(kù) | 磷酸酶抑制劑化合物庫(kù) | 高選擇性抑制劑庫(kù) | 臨床前化合物庫(kù) | 糖代謝化合物庫(kù) | 口服活性化合物庫(kù) | 表型篩選靶點(diǎn)鑒定庫(kù) |