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GSK2110183
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
GSK2110183图片
CAS NO:1047634-63-8
规格:≥98%
包装与价格:
包装价格(元)
5mg电议
10mg电议
25mg电议
50mg电议
100mg电议
250mg电议
500mg电议

产品介绍
理化性质和储存条件
Molecular Weight (MW)445.31
FormulaC18H16Cl2F2N4OS
CAS No.1047634-63-8;
Storage-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)DMSO: 10 mM
Water: <1 mg/mL
Ethanol: <1 mg/mL
SMILESO=C(C1=CC(C2=C(Cl)C=NN2C)=C(Cl)S1)N[C@@H](CC3=CC=C(F)C(F)=C3)CN
Synonyms/Chemical NameGSK2110183; GSK-2110183; GSK 2110183; N-[(2S)-1-amino-3-(3-fluorophenyl)propan-2-yl]-5-chloro-4-(4-chloro-2-methylpyrazol-3-yl)thiophene-2-carboxamide; Afuresertib-F
实验参考方法
In Vitro

Kinase Assay: the potency of compounds against Akt enzymes is measured. Since GSK2110183 and GSK2141795 are highly potent inhibitors of the 3 isoforms of Akt, the true potency (Ki) of the inhibitors is initially determined at low enzyme concentrations (0.1 nM Akt1, 0.7 nM Akt2, and 0.2 nM Akt3) using a filter binding assay and then confirmed with progress curve analysis. In the filter binding assay, a pre-mix of enzyme plus inhibitor is incubated for 1 h and then added to a GSKα peptide (Ac-KKGGRARTSSFAEPG-amide) and [γ33P] ATP. Reactions are terminated after 2 h and the radio labeled Akt peptide product is captured in a phospho-cellulose filter plate. Progress curve analysis utilized continuous real-time fluorescence detection of product formation using the Sox-Akt-tide substrate (Ac-ARKRERAYSF-d-Pro-Sox-Gly-NH2).


Cell Assay: A 3-day proliferation assay using CellTiter-Glo is performed to measure the growth inhibition by the compounds at 0-30 μM. Cell growth is determined relative to untreated (DMSO) controls. EC50’s are calculated from inhibition curves using a 4- or 6-parameter fitting algorithm in the Assay Client application. Cells used: Hematological cell lines and solid tumor cell lines

Afuresertib inhibits the kinase activity of the E17K AKT1 mutant protein with EC50 of 0.2 nM. Afuresertib shows a concentration-dependent effect on multiple AKT substrate phosphorylation levels, including GSK3b, PRAS40, FOXO and Caspase 9. Overall 65% of the hematological cell lines are sensitive to afuresertib (EC50 < 1 μM). Among tested solid tumor cell lines, 21% have EC50 < 1 μM in response to afuresertib.

In VivoMice bearing BT474 breast tumor xenografts are dosed orally with either vehicle or GSK2110183 at 10, 30 or 100 mg/kg daily for 21 days which result in 8, 37 and 61% TGI, respectively. Mice tolerated GSK2110183 well, with 1-3% body weight loss reported after 5 days of dosing which recover over the course of the study. Other tumor xenograft models which possess an activation of the Akt pathway are explored to further demonstrate compound efficacy. Mice treated with GSK2110183 at 10, 30 and 100 mg/kg result in 23, 37 and 97% TGI, respectively, of SKOV3 xenografts.
Animal modelMice bearing BT474 breast tumor xenografts
Formulation & DosageDissolved in 20% polyethylene glycol (PEG) 400/1% DMSO; 10, 30 or 100 mg/kg; p.o.
References[1] Dumble M, et al. PLoS One, 2014, 9(6):e100880.