| Name | Vevorisertib trihydrochloride |
| Description | Vevorisertib trihydrochloride (ARQ 751 trihydrochloride) is a selective and potent inhibitor of pan-AKT and AKT1-E17K mutations, inhibiting AKT1, AKT2 and AKT3. Vevorisertib trihydrochloride is used in the study of hepatocellular carcinoma and advanced solid tumours. |
| In vitro | Vevorisertib trihydrochloride (0、12、33、111、333、1000 nM，2小時)抑制AKT1-E17K的磷酸化[2]。無論是否存在生長因子，Vevorisertib trihydrochloride (1 μM，2小時；NIH 3T3細胞轉染pcDNAAKT-WT-GFP或pcDNA-E17K-GFP)均能抑制AKT-WT和AKT1-E17K的質(zhì)膜轉移[2]。Vevorisertib trihydrochloride (5 μM)表現(xiàn)出對全長AKT1 57%的抑制作用[1]。Vevorisertib trihydrochloride (0、0.012、0.037、0.11、0.33、1 μM；2小時)對mTORC1及AKT直接底物（包括PRAS40、GSK3β、FOXO、BAD及AS160）顯示出劑量依賴性效應，適用于癌細胞系[2]。Vevorisertib trihydrochloride 對食管癌、乳腺癌和頭頸癌細胞具有抗增殖作用(GI 50 < 1 μM)[1]。在PIK3CA突變細胞系中，Vevorisertib trihydrochloride 展現(xiàn)強烈的抗增殖活性[2]。Vevorisertib trihydrochloride (MK-4440)/伊馬替尼美西酸鹽(IM)組合能促進胃腸間質(zhì)瘤(GIST)細胞周期阻滯，并增加細胞死亡率[1]。再次強調(diào)，在PIK3CA突變細胞系中，Vevorisertib trihydrochloride 顯著抑制細胞增殖[2]：乳腺癌細胞系的GI 50 (nM)數(shù)據(jù)表明，與PIK3CA、ER、PR、HER2狀態(tài)相關的各細胞系均對Vevorisertib trihydrochloride 敏感。Western Blot分析[1][2]顯示，Vevorisertib trihydrochloride 能夠抑制AKT1-E17K的磷酸化，并對mTORC1及AKT直接底物表現(xiàn)出劑量依賴性抑制效應，展現(xiàn)了其對各類癌細胞系具有廣泛的抑制作用。 |
| In vivo | Vevorisertib trihydrochloride 以(25, 50和75 mg/kg; 口服; 5天給藥后休藥4天，共20天)的劑量展現(xiàn)了分別為68%, 78%和98%的強效腫瘤生長抑制作用[2]。在連續(xù)10天每天口服Vevorisertib trihydrochloride (5, 10, 20, 40, 80, 和120 mg/kg)的實驗中，分別顯示了29%, 33%, 50%, 73%, 83%, 和92%的腫瘤生長抑制效果[2]。Vevorisertib trihydrochloride 達到的最高血漿濃度(Cmax)超過2μM[2]。在高至120 mg/kg的劑量水平下，Vevorisertib trihydrochloride 通常具有良好的耐受性[2]。Vevorisertib trihydrochloride 與MK-4440/IM聯(lián)合使用，在GIST的IM敏感前臨床模型中，相較于單藥治療展現(xiàn)出了更高的療效[1]。動物模型為內(nèi)膜PDX裸鼠異種移植模型(AKT1-E17K突變腫瘤組織亞皮下植入無胸腺裸鼠;腫瘤體積約200 mm^3)[2]，劑量為25, 50和75 mg/kg，給藥方式為口服; 5天給藥后休藥4天，共20天，結果顯示了68%, 78%和98%的腫瘤生長抑制作用。AN3CA鼠異種移植模型(攜帶250 mm^3腫瘤的雌性NCr nu/nu鼠)[2]，劑量為5, 10, 20, 40, 80, 和120 mg/kg，給藥方式為每天口服，持續(xù)十天，顯示了29%, 33%, 50%, 73%, 83%, 和92%的腫瘤生長抑制效果。 |
| Storage | store at low temperature,keep away from direct sunlight | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| Solubility Information | H2O : 20 mg/mL (28.73 mM)
DMSO : 100 mg/mL (143.66 mM), Sonication is recommended.
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| Keywords | ARQ-751 Trihydrochloride | ARQ751 Trihydrochloride | ARQ751 | ARQ-751 | ARQ 751 | Vevorisertib | Vevorisertib trihydrochloride |
| Inhibitors Related | (E)-Akt inhibitor-IV | Honokiol | Capivasertib | Methyl-Hesperidin | AKT Kinase Inhibitor | Artemisinin | 2,3-Butanediol | PI3K/Akt/mTOR-IN-2 | Oridonin | Ethyl gallate | Urolithin B | SKLB-163 |
| Related Compound Libraries | Inhibitor Library | Bioactive Compound Library | Bioactive Compounds Library Max | Kinase Inhibitor Library | Anti-Aging Compound Library |