Afuresertib HCl - 半岛电竞官方网址

Molecular Weight (MW)	463.78
Formula	C18H18Cl3FN4OS
CAS No.	1047645-82-8 (HCl)
Storage	-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility(In vitro)	DMSO: 85 mg/mL (198.9 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
SMILES	O=C(C1=CC(C2=C(Cl)C=NN2C)=C(Cl)S1)N[C@@H](CC3=CC=CC(F)=C3)CN.[H]Cl
Synonyms/Chemical Name	GSK2110183B; GSK-2110183B; GSK 2110183B; GSK-2110183; GSK2110183; GSK2110183 B HCl; GSK2110183-B; GSK2110183B; N-[(2S)-1-amino-3-(3-fluorophenyl)propan-2-yl]-5-chloro-4-(4-chloro-2-methylpyrazol-3-yl)thiophene-2-carboxamide

Molecular Weight (MW)

463.78

Formula

C18H18Cl3FN4OS

CAS No.

1047645-82-8 (HCl)

Storage

-20℃ for 3 years in powder form

-80℃ for 2 years in solvent

Solubility(In vitro)

DMSO: 85 mg/mL (198.9 mM)

Water: <1 mg/mL

Ethanol: <1 mg/mL

SMILES

O=C(C1=CC(C2=C(Cl)C=NN2C)=C(Cl)S1)N[C@@H](CC3=CC=CC(F)=C3)CN.[H]Cl

Synonyms/Chemical Name

GSK2110183B; GSK-2110183B; GSK 2110183B; GSK-2110183; GSK2110183; GSK2110183 B HCl; GSK2110183-B; GSK2110183B; N-[(2S)-1-amino-3-(3-fluorophenyl)propan-2-yl]-5-chloro-4-(4-chloro-2-methylpyrazol-3-yl)thiophene-2-carboxamide

In Vitro	Kinase Assay: The true potency (Ki*) of the inhibitor 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-KKGGRARTSS-FAEPG-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 utilizes 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 Vivo	Mice bearing BT474 breast tumor xenografts are dosed with afuresertib (p.o.) at 10, 30 or 100 mg/kg daily which results in 8, 37 and 61% TGI, respectively. Mice bearing SKOV3 ovarian tumor xenografts are treated with 10, 30 and 100 mg/kg afuresertib which results in 23, 37 and 97% TGI, respectively
Animal model	Female athymic nude and SCID mice bearing SKOV3 or BT474 tumors
Formulation & Dosage	Dissolved in 20% polyethylene glycol (PEG) 400/1% DMSO; 25, 50, 100 mg/kg; p.o.
References	[1] Dumble M, et al. PLoS One, 2014, 9(6):e100880.

In Vitro

Kinase Assay: The true potency (Ki*) of the inhibitor 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-KKGGRARTSS-FAEPG-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 utilizes 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 Vivo

Mice bearing BT474 breast tumor xenografts are dosed with afuresertib (p.o.) at 10, 30 or 100 mg/kg daily which results in 8, 37 and 61% TGI, respectively. Mice bearing SKOV3 ovarian tumor xenografts are treated with 10, 30 and 100 mg/kg afuresertib which results in 23, 37 and 97% TGI, respectively

Animal model

Female athymic nude and SCID mice bearing SKOV3 or BT474 tumors

Formulation & Dosage

Dissolved in 20% polyethylene glycol (PEG) 400/1% DMSO; 25, 50, 100 mg/kg; p.o.

References

[1] Dumble M, et al. PLoS One, 2014, 9(6):e100880.

CAS NO:	1047645-82-8
规格:	≥98%

包装	价格(元)
1mg	电议
2mg	电议
5mg	电议
10mg	电议
25mg	电议
50mg	电议
100mg	电议
250mg	电议
500mg	电议