| Identification | Back Directory | [Name]
Acetamide, N-[1-[3-[3-[4-(1-aminocyclobutyl)phenyl]-2-(2-amino-3-pyridinyl)-3H-imidazo[4,5-b]pyridin-5-yl]phenyl]-4-piperidinyl]-N-methyl-, hydrochloride (1:3) | [CAS]
1416775-08-0 | [Synonyms]
Acetamide, N-[1-[3-[3-[4-(1-aminocyclobutyl)phenyl]-2-(2-amino-3-pyridinyl)-3H-imidazo[4,5-b]pyridin-5-yl]phenyl]-4-piperidinyl]-N-methyl-, hydrochloride (1:3) | [Molecular Formula]
C35H39ClN8O | [MOL File]
1416775-08-0.mol | [Molecular Weight]
623.2 |
| Chemical Properties | Back Directory | [storage temp. ]
4°C, away from moisture | [solubility ]
DMSO : 150 mg/mL (215.48 mM; Need ultrasonic) | [form ]
Solid | [color ]
White to yellow |
| Hazard Information | Back Directory | [Uses]
Vevorisertib (ARQ 751) trihydrochloride is a selective, allosteric, pan-AKT and AKT1-E17K mutant inhibitors. Vevorisertib trihydrochloride potently inhibit phosphorylation of AKT. Vevorisertib trihydrochloride has Kd values of 1.2 nM and 8.6 nM for AKT1 and AKT1-E17K, respectively. Vevorisertib trihydrochloride has IC50 values of 0.55, 0.81, and 1.3 nM for AKT1, AKT2, and AKT3, respectively. Vevorisertib trihydrochloride can be used for the research of cancer[1]. | [Biological Activity]
Vevorisertib (ARQ 751) trihydrochloride is a selective, allosteric, pan-AKT and AKT1-E17K mutant inhibitors. Vevorisertib trihydrochloride potently inhibit phosphorylation of AKT. Vevorisertib trihydrochloride has Kd values of 1.2 nM and 8.6 nM for AKT1 and AKT1-E17K, respectively. Vevorisertib trihydrochloride has IC50 values of 0.55, 0.81, and 1.3 nM for AKT1, AKT2, and AKT3, respectively. Vevorisertib trihydrochloride can be used for the research of cancer[1].
Vevorisertib trihydrochloride (0, 12, 33, 111, 333, 1000 nM, 2 hours) inhibits phosphorylation of AKT1-E17K[1].Vevorisertib trihydrochloride (1 μM for 2 hours; NIH 3T3 cells are transfected with either pcDNAAKT-WT-GFP or pcDNA-E17K-GFP) inhibits plasma membrane translocation of AKT-WT and AKT1-E17K irrespective of the presence of growth factors[1].Vevorisertib trihydrochloride (5 μM) exhibites 57% inhibition of full-length AKT1[1].Vevorisertib trihydrochloride (0, 0.012, 0.037, 0.11, 0.33, 1 μM; 2 hours) shows a dose-dependent effect on mTORC1 and AKT direct substrates including PRAS40, GSK3β, FOXO, BAD, and AS160 in cancer cell lines[1].Vevorisertib trihydrochloride has anti-proliferative effect on esophageal, breast, and head and neck cancer cells (GI50 < 1 μM)[1].Vevorisertib trihydrochloride exhibits strong anti-proliferative activity in PIK3CA mutant cell lines[1].Vevorisertib trihydrochloride (MK-4440)/imatinib mesylate (IM) combination shows cell cycle arrest, and increases cell death of gastrointestinal stromal tumor (GIST) cells[2].Vevorisertib trihydrochloride exhibits strong anti-proliferative activity in PIK3CA mutant cell lines[1]: Breast Cancer Cell Lines GI50 (nM) PIK3CA ER PR HER2 T47D 1.05 H1047R + + - EFM-19 1.54 H1047R + + - MCF-7 2.20 E545K + + - BT474 3.25 K111N + + + MDA-MB-453 6.05 H1047R - - +
Vevorisertib trihydrochloride (25, 50 and 75 mg/kg; p.o.; 5 days dosing followed by a 4 day dosing holiday for 20 days) shows potent tumor growth inhibition of 68, 78 and 98%, respectively[1].Vevorisertib trihydrochloride (5, 10, 20, 40, 80, and 120 mg/kg; p.o. daily for ten days) shows tumor growth inhibition of 29, 33, 50, 73, 83, and 92%, respectively[1].Vevorisertib trihydrochloride reachs Cmax plasma concentrations of ≥2 μM[1].Vevorisertib trihydrochloride is generally well-tolerated at dose levels up to 120 mg/kg[1].Vevorisertib trihydrochloride (MK-4440)/IM combination shows superior efficacy in an IM-sensitive preclinical model of GIST compared with either single agent[2]. | [in vivo]
Vevorisertib trihydrochloride (25, 50 and 75 mg/kg; p.o.; 5 days dosing followed by a 4 day dosing holiday for 20 days) shows potent tumor growth inhibition of 68, 78 and 98%, respectively[1].
Vevorisertib trihydrochloride (5, 10, 20, 40, 80, and 120 mg/kg; p.o. daily for ten days) shows tumor growth inhibition of 29, 33, 50, 73, 83, and 92%, respectively[1].
Vevorisertib trihydrochloride reachs Cmax plasma concentrations of ≥2 μM[1].
Vevorisertib trihydrochloride is generally well-tolerated at dose levels up to 120 mg/kg[1].
Vevorisertib trihydrochloride (MK-4440)/IM combination shows superior efficacy in an IM-sensitive preclinical model of GIST compared with either single agent[2]. | Animal Model: | Endometrial PDX mouse xenograft models (AKT1-E17K mutation tumor fragments subcutaneously implanted in athymic nude mice; tumor volume of approximately 200 mm3)[1] | | Dosage: | 25, 50 and 75 mg/kg | | Administration: | p.o.; 5 days dosing followed by a 4 day dosing holiday for 20 days | | Result: | Showed potent tumor growth inhibition of 68, 78 and 98%, respectively. |
| Animal Model: | AN3CA mouse xenograft models (female NCr nu/nu mice with 250 mm3 tumors size)[1] | | Dosage: | 5, 10, 20, 40, 80, and 120 mg/kg | | Administration: | p.o.; daily for ten days | | Result: | Showed tumor growth inhibition of 29, 33, 50, 73, 83, and 92%, respectively. |
| [IC 50]
Akt1: 0.55 nM (IC50); Akt2: 0.81 nM (IC50); Akt3: 1.31 nM (IC50); Akt1: 1.2 nM (Kd); Akt1E17K: 8.6 nM (Kd) | [storage]
4°C, away from moisture | [References]
[1]. Yu Y, et al. Targeting AKT1-E17K and the PI3K/AKT Pathway with an Allosteric AKT Inhibitor, ARQ 092. PLoS One. 2015 Oct 15;10(10):e0140479. [2]. Kozinova M, et al. Combined Inhibition of AKT and KIT Restores Expression of Programmed Cell Death 4 (PDCD4) in Gastrointestinal Stromal Tumor. Cancers (Basel). 2021 Jul 23;13(15):3699. |
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