Vevorisertib trihydrochloride

SKU: orb1691730

Description

Vevorisertib trihydrochloride is a potent, selective pan-AKT inhibitor that also targets the AKT1-E17K mutant. It is used in research for advanced solid tumors and hepatocellular carcinoma, with studies demonstrating its activity in both in vitro and in vivo experimental models.

Research Area

Signal Transduction

Key Properties

• CAS Number: 1416775-08-0
• MW: 696.12
• Purity: 98.28% (May vary between batches)
• Formula: C₃₅H₄₁Cl₃N₈O
• SMILES: Cl.Cl.Cl.CN(C1CCN(CC1)c1cccc(c1)-c1ccc2nc(-c3cccnc3N)n(-c3ccc(cc3)C3(N)CCC3)c2n1)C(C)=O
• Target: Akt
• Solubility: DMSO:100 mg/mL (143.65 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:5 mg/mL (7.18 mM);H2O:20 mg/mL (28.73 mM)

Bioactivity

• Target IC50:
  Akt1 (E17K):8.6 nM (Kd)|Akt2:0.81 nM|Akt1:1.2 nM (Kd)|Akt1:0.55 nM|Akt3:1.31 nM
• 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.
• 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.

Storage & Handling

• 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.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

ARQ751 Trihydrochloride, ARQ-751 Trihydrochloride, ARQ751, ARQ-751, ARQ 751, ARQ 751 trihydrochloride, Akt, P-Akt, Vevorisertib trihydrochloride, Vevorisertib

Compound Identifiers

PubChem CID

131746460