Home PI3K/Akt/mTOR Akt inhibitor Afuresertib (GSK2110183) For research use only.

Afuresertib (GSK2110183)

Afuresertib (GSK2110183) is a potent, orally bioavailable Akt inhibitor with Ki of 0.08 nM, 2 nM, and 2.6 nM for Akt1, Akt2, and Akt3, respectively. Phase 2.

Afuresertib (GSK2110183) Chemical Structure

Afuresertib (GSK2110183) Chemical Structure

CAS No. 1047644-62-1

Purity & Quality Control

Afuresertib (GSK2110183) Related Products

Signaling Pathway

Akt Signaling Pathways

Akt Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
Sf9 Function assay 40 mins Inhibition of full length human AKT1 expressed in Sf9 cells assessed as reduction in substrate phosphorylation using biotin-ahx-ARKRERAYSFGHHA-amide substrate and [gamma-33P]ATP incubated for 40 mins by top count microplate scintillation counting method, IC50 = 0.001 μM. ChEMBL
Sf9 Function assay 40 mins Inhibition of full length human AKT3 expressed in Sf9 cells assessed as reduction in substrate phosphorylation using biotin-ahx-ARKRERAYSFGHHA-amide substrate and [gamma-33P]ATP incubated for 40 mins by top count microplate scintillation counting method, IC50 = 0.001585 μM. ChEMBL
COLO205 Growth inhibition assay 72 hrs Growth inhibition of human COLO205 cells at 1:10 molar ratio of compound in presence of N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl- 2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide incubated for 72 hrs , IC50 = 0.009 μM. ChEMBL
Sf9 Function assay 40 mins Inhibition of full length human AKT2 expressed in Sf9 cells assessed as reduction in substrate phosphorylation using biotin-ahx-ARKRERAYSFGHHA-amide substrate and [gamma-33P]ATP incubated for 40 mins by top count microplate scintillation counting method, IC50 = 0.01 μM. ChEMBL
MV522 Growth inhibition assay 72 hrs Growth inhibition of human MV522 cells at 1:10 molar ratio of compound in presence of N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl- 2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide incubated for 72 hrs, IC50 = 0.012 μM. ChEMBL
HT-29 Growth inhibition assay 72 hrs Growth inhibition of human HT-29 cells at 1:10 molar ratio of compound in presence of N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl- 2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide incubated for 72 hrs, IC50 = 0.015 μM. ChEMBL
NCI-H727 Growth inhibition assay 72 hrs Growth inhibition of human NCI-H727 cells at 1:10 molar ratio of compound in presence of N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl- 2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide incubated for 72 hrs, IC50 = 0.019 μM. ChEMBL
SW1417 Growth inhibition assay 72 hrs Growth inhibition of human SW1417 cells at 1:10 molar ratio of compound in presence of N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl- 2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide incubated for 72 hrs, IC50 = 0.03 μM. ChEMBL
Calu6 Growth inhibition assay 72 hrs Growth inhibition of human Calu6 cells at 1:10 molar ratio of compound in presence of N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl- 2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide incubated for 72 hrs, IC50 = 0.031 μM. ChEMBL
LS1034 Growth inhibition assay 72 hrs Growth inhibition of human LS1034 cells at 1:10 molar ratio of compound in presence of N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl- 2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide incubated for 72 hrs, IC50 = 0.04 μM. ChEMBL
SW1463 Growth inhibition assay 72 hrs Growth inhibition of human SW1463 cells at 1:10 molar ratio of compound in presence of N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl- 2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide incubated for 72 hrs, IC50 = 0.041 μM. ChEMBL
RKO Growth inhibition assay 72 hrs Growth inhibition of human RKO cells at 1:10 molar ratio of compound in presence of N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl- 2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide incubated for 72 hrs, IC50 = 0.054 μM. ChEMBL
NCI-H508 Growth inhibition assay 72 hrs Growth inhibition of human NCI-H508 cells at 1:10 molar ratio of compound in presence of N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl- 2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide incubated for 72 hrs, IC50 = 0.08 μM. ChEMBL
NCI-H1155 Growth inhibition assay 72 hrs Growth inhibition of human NCI-H1155 cells at 1:10 molar ratio of compound in presence of N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl- 2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide incubated for 72 hr, IC50 = 0.101 μM. ChEMBL
A427 Growth inhibition assay 72 hrs Growth inhibition of human A427 cells at 1:10 molar ratio of compound in presence of N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl- 2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide incubated for 72 hrs, IC50 = 0.103 μM. ChEMBL
KM12 Growth inhibition assay 72 hrs Growth inhibition of human KM12 cells at 1:10 molar ratio of compound in presence of N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl- 2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide incubated for 72 hrs, IC50 = 0.104 μM. ChEMBL
HCT8 Growth inhibition assay 72 hrs Growth inhibition of human HCT8 cells at 1:10 molar ratio of compound in presence of N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl- 2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide incubated for 72 hrs, IC50 = 0.143 μM. ChEMBL
MDA-MB-175-VII Growth inhibition assay 72 hrs Growth inhibition of human MDA-MB-175-VII cells at 1:10 molar ratio of compound in presence of N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl- 2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide incubated for 72 hrs, IC50 = 0.155 μM. ChEMBL
A549 Growth inhibition assay 72 hrs Growth inhibition of human A549 cells at 1:10 molar ratio of compound in presence of N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl- 2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide incubated for 72 hrs, IC50 = 0.164 μM. ChEMBL
NCI-H23 Growth inhibition assay 72 hrs Growth inhibition of human NCI-H23 cells at 1:10 molar ratio of compound in presence of N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl- 2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide incubated for 72 hrs , IC50 = 0.199 μM. ChEMBL
SW837 Growth inhibition assay 72 hrs Growth inhibition of human SW837 cells at 1:10 molar ratio of compound in presence of N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl- 2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide incubated for 72 hrs, IC50 = 0.248 μM. ChEMBL
SW480 Growth inhibition assay 72 hrs Growth inhibition of human SW480 cells at 1:10 molar ratio of compound in presence of N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl- 2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide incubated for 72 hrs, IC50 = 0.259 μM. ChEMBL
NCI-H1355 Growth inhibition assay 72 hrs Growth inhibition of human NCI-H1355 cells at 1:10 molar ratio of compound in presence of N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl- 2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide incubated for 72 hr, IC50 = 0.268 μM. ChEMBL
EFM19 Growth inhibition assay 72 hrs Growth inhibition of human EFM19 cells at 1:10 molar ratio of compound in presence of N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl- 2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide incubated for 72 hrs, IC50 = 0.3 μM. ChEMBL
T84 Growth inhibition assay 72 hrs Growth inhibition of human T84 cells at 1:10 molar ratio of compound in presence of N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl- 2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide incubated for 72 hrs, IC50 = 0.304 μM. ChEMBL
COR-L23 Growth inhibition assay 72 hrs Growth inhibition of human COR-L23 cells at 1:10 molar ratio of compound in presence of N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl- 2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide incubated for 72 hrs , IC50 = 0.368 μM. ChEMBL
NCI-H1792 Growth inhibition assay 72 hrs Growth inhibition of human NCI-H1792 cells at 1:10 molar ratio of compound in presence of N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl- 2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide incubated for 72 hr, IC50 = 0.374 μM. ChEMBL
SW1573 Growth inhibition assay 72 hrs Growth inhibition of human SW1573 cells at 1:10 molar ratio of compound in presence of N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl- 2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide incubated for 72 hrs, IC50 = 0.382 μM. ChEMBL
Calu3 Growth inhibition assay 72 hrs Growth inhibition of human Calu3 cells at 1:10 molar ratio of compound in presence of N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl- 2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide incubated for 72 hrs, IC50 = 0.392 μM. ChEMBL
HCC827 Growth inhibition assay 72 hrs Growth inhibition of human HCC827 cells at 1:10 molar ratio of compound in presence of N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl- 2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide incubated for 72 hrs, IC50 = 0.401 μM. ChEMBL
EFM19 Growth inhibition assay 72 hrs Growth inhibition of human EFM19 cells incubated for 72 hrs by Cell-titer-Glo reagent based assay, IC50 = 0.43 μM. ChEMBL
HOP62 Growth inhibition assay 72 hrs Growth inhibition of human HOP62 cells at 1:10 molar ratio of compound in presence of N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl- 2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide incubated for 72 hrs, IC50 = 0.498 μM. ChEMBL
NCI-H508 Growth inhibition assay 72 hrs Growth inhibition of human NCI-H508 cells incubated for 72 hrs by Cell-titer-Glo reagent based assay, IC50 = 0.522 μM. ChEMBL
SW900 Growth inhibition assay 72 hrs Growth inhibition of human SW900 cells at 1:10 molar ratio of compound in presence of N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl- 2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide incubated for 72 hrs, IC50 = 0.719 μM. ChEMBL
MDA-MB-175-VII Growth inhibition assay 72 hrs Growth inhibition of human MDA-MB-175-VII cells incubated for 72 hrs by Cell-titer-Glo reagent based assay, IC50 = 0.794 μM. ChEMBL
NCI-H1155 Growth inhibition assay 72 hrs Growth inhibition of human NCI-H1155 cells incubated for 72 hrs by Cell-titer-Glo reagent based assay, IC50 = 0.865 μM. ChEMBL
DLD1 Growth inhibition assay 72 hrs Growth inhibition of human DLD1 cells at 1:10 molar ratio of compound in presence of N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl- 2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide incubated for 72 hrs, IC50 = 0.932 μM. ChEMBL
HT-29 Growth inhibition assay 72 hrs Growth inhibition of human HT-29 cells incubated for 72 hrs by Cell-titer-Glo reagent based assay, IC50 = 1.383 μM. ChEMBL
HCT8 Growth inhibition assay 72 hrs Growth inhibition of human HCT8 cells incubated for 72 hrs by Cell-titer-Glo reagent based assay, IC50 = 1.541 μM. ChEMBL
RKO Growth inhibition assay 72 hrs Growth inhibition of human RKO cells incubated for 72 hrs by Cell-titer-Glo reagent based assay, IC50 = 1.806 μM. ChEMBL
Calu6 Growth inhibition assay 72 hrs Growth inhibition of human Calu6 cells incubated for 72 hrs by Cell-titer-Glo reagent based assay, IC50 = 2.154 μM. ChEMBL
KM12 Growth inhibition assay 72 hrs Growth inhibition of human KM12 cells incubated for 72 hrs by Cell-titer-Glo reagent based assay, IC50 = 2.247 μM. ChEMBL
COLO205 Growth inhibition assay 72 hrs Growth inhibition of human COLO205 cells incubated for 72 hrs by Cell-titer-Glo reagent based assay, IC50 = 2.567 μM. ChEMBL
MV522 Growth inhibition assay 72 hrs Growth inhibition of human MV522 cells incubated for 72 hrs by Cell-titer-Glo reagent based assay, IC50 = 3.044 μM. ChEMBL
LS1034 Growth inhibition assay 72 hrs Growth inhibition of human LS1034 cells incubated for 72 hrs by Cell-titer-Glo reagent based assay, IC50 = 4.339 μM. ChEMBL
NCI-H727 Growth inhibition assay 72 hrs Growth inhibition of human NCI-H727 cells incubated for 72 hrs by Cell-titer-Glo reagent based assay, IC50 = 4.799 μM. ChEMBL
COR-L23 Growth inhibition assay 72 hrs Growth inhibition of human COR-L23 cells incubated for 72 hrs by Cell-titer-Glo reagent based assay, IC50 = 5.373 μM. ChEMBL
A549 Growth inhibition assay 72 hrs Growth inhibition of human A549 cells incubated for 72 hrs by Cell-titer-Glo reagent based assay, IC50 = 5.993 μM. ChEMBL
NCI-H1355 Growth inhibition assay 72 hrs Growth inhibition of human NCI-H1355 cells incubated for 72 hrs by Cell-titer-Glo reagent based assay, IC50 = 6.685 μM. ChEMBL
NCI-H23 Growth inhibition assay 72 hrs Growth inhibition of human NCI-H23 cells incubated for 72 hrs by Cell-titer-Glo reagent based assay, IC50 = 7.124 μM. ChEMBL
NCI-H1792 Growth inhibition assay 72 hrs Growth inhibition of human NCI-H1792 cells incubated for 72 hrs by Cell-titer-Glo reagent based assay, IC50 = 7.307 μM. ChEMBL
SW1463 Growth inhibition assay 72 hrs Growth inhibition of human SW1463 cells incubated for 72 hrs by Cell-titer-Glo reagent based assay, IC50 = 9.725 μM. ChEMBL
Click to View More Cell Line Experimental Data

Biological Activity

Description Afuresertib (GSK2110183) is a potent, orally bioavailable Akt inhibitor with Ki of 0.08 nM, 2 nM, and 2.6 nM for Akt1, Akt2, and Akt3, respectively. Phase 2.
Targets
Akt1 [1]
(Cell-free assay)		 Akt2 [1]
(Cell-free assay)		 Akt3 [1]
(Cell-free assay)
0.08 nM(Ki) 2 nM(Ki) 2.6 nM(Ki)
In vitro
In vitro 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.[1]
Kinase Assay Potency (Ki*) of afuresertib
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 Research Cell lines Hematological cell lines and solid tumor cell lines
Concentrations 30 μM
Incubation Time 72 h
Method 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.
Experimental Result Images Methods Biomarkers Images PMID
Western blot p-GSK3 / GSK3 / p-PRAS40 / PRAS40 / p-FOXO / p-Casp9 / p-AKT / AKT / p-MEK / p-ERK / Erk ATG3 / ATG12 / LC3B 24978597
In Vivo
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.[1]
Animal Research Animal Models Female athymic nude and SCID mice bearing SKOV3 or BT474 tumors
Dosages 100 mg/kg
Administration p.o.
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT05489744 Completed
Healthy Volunteer
Laekna Limited
 August 6 2022 Phase 1
NCT05390710 Completed
Solid Tumor|TNBC - Triple-Negative Breast Cancer
Laekna Limited
 June 12 2021 Phase 1
NCT04374630 Active not recruiting
Platinum-resistant Ovarian Cancer
Laekna Limited
 June 9 2020 Phase 2
NCT04060394 Active not recruiting
Metastatic Castration-resistant Prostate Cancer
Laekna Limited
 September 13 2019 Phase 1|Phase 2
NCT02235740 Terminated
Cancer
Novartis|Amgen
 November 2014 Phase 1

Chemical Information & Solubility

Molecular Weight 427.32 Formula

C18H17Cl2FN4OS
CAS No. 1047644-62-1 SDF Download Afuresertib (GSK2110183) SDF
Smiles CN1C(=C(C=N1)Cl)C2=C(SC(=C2)C(=O)NC(CC3=CC(=CC=C3)F)CN)Cl
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 85 mg/mL ( (198.91 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 85 mg/mL

Water : Insoluble


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In vivo
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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

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