| 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 at concentrations ranging from 0 to 1000 nM over 2 hours inhibits the phosphorylation of AKT1-E17K. In NIH 3T3 cells transfected with pcDNAAKT-WT-GFP or pcDNA-E17K-GFP and treated with 1 μM of the compound for the same duration, it prevents the plasma membrane translocation of both AKT-WT and AKT1-E17K, regardless of growth factor presence. Additionally, a 5 μM concentration results in 57% inhibition of full-length AKT1. The compound demonstrates a dose-dependent impact on mTORC1 and AKT substrates, such as PRAS40, GSK3β, FOXO, BAD, and AS160 across various cancer cell lines with distinct concentrations (0 to 1 μM, 2 hours). It also exhibits significant anti-proliferative effects on esophageal, breast, and head and neck cancer cells, with GI 50 values below 1 μM, and showcases potent efficacy in PIK3CA mutant cell lines. Moreover, a combination of Vevorisertib trihydrochloride (MK-4440) and imatinib mesylate leads to cell cycle arrest and increased cell death in gastrointestinal stromal tumor cells. Western Blot analyses reveal the compound's effectiveness in inhibiting phosphorylation of AKT1-E17K and dose-dependent effects on mTORC1 and AKT substrates across different cell lines, including those with PIK3CA mutations and various cancer-related mutations. |
| In vivo | Vevorisertib trihydrochloride administered orally at doses of 25, 50, and 75 mg/kg for five consecutive days followed by a four-day break over a 20-day period demonstrated significant tumor growth inhibition rates of 68%, 78%, and 98%, respectively, in endometrial PDX mouse xenograft models featuring the AKT1-E17K mutation. When administered daily at varying doses (5, 10, 20, 40, 80, and 120 mg/kg) for ten days in AN3CA mouse xenograft models, it showed tumor growth inhibition rates ranging from 29% to 92%. The compound achieved C max plasma concentrations of ≥2 μM and was generally well-tolerated at all administered doses up to 120 mg/kg. Additionally, a combination of Vevorisertib trihydrochloride (MK-4440) and IM exhibited superior efficacy in an IM-sensitive preclinical GIST model compared to either agent alone, highlighting its potential as a robust therapeutic candidate in specific cancer models. |
| 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/Shipping at ambient temperature. |
| Solubility Information | H2O : 20 mg/mL (28.73 mM), Sonication is recommended.
DMSO : 100 mg/mL (143.66 mM), Sonication is recommended.
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| Keywords | Vevorisertib trihydrochloride | Vevorisertib | P-Akt | ARQ-751 Trihydrochloride | ARQ751 Trihydrochloride | ARQ-751 | ARQ751 | ARQ 751 | Akt |
| Inhibitors Related | Ethyl gallate | Oridonin | Capivasertib | SKLB-163 | Scutellarin | Methyl-Hesperidin | Artemisinin | Honokiol | (E)-Akt inhibitor-IV | 2,3-Butanediol | MK-2206 dihydrochloride | AKT Kinase Inhibitor |
| Related Compound Libraries | PI3K-AKT-mTOR Compound Library | Anti-Lung Cancer Compound Library | Reprogramming Compound Library | Failed Clinical Trials Compound Library | Anti-Pancreatic Cancer Compound Library | Bioactive Compound Library | Kinase Inhibitor Library | Autophagy Compound Library | Inhibitor Library | Anti-Aging Compound Library | Immunology/Inflammation Compound Library | Bioactive Compounds Library Max |
United States
