Home PI3K/Akt/mTOR Akt inhibitor Uprosertib (GSK2141795) For research use only.

Uprosertib (GSK2141795)

Synonyms: GSK795

Uprosertib (GSK2141795, GSK795) is a selective, ATP-competitive, and orally bioavailable Akt inhibitor with IC50 of 180 nM, 328 nM, and 38 nM for Akt 1, 2 and 3, respectively. Phase 2.

Uprosertib (GSK2141795) Chemical Structure

Uprosertib (GSK2141795) Chemical Structure

CAS No. 1047634-65-0

Purity & Quality Control

Uprosertib (GSK2141795) Related Products

Signaling Pathway

Akt Signaling Pathways

Akt Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
OVCAR8 Antiproliferative assay Antiproliferative activity against human OVCAR8 cells, IC50=0.24μM 31298542
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=0.001995μM ChEMBL
JVM2 Antiproliferative assay Antiproliferative activity against human JVM2 cells assessed as reduction in cell viability, IC50=0.293μM 31301565
KB-3-1 qHTS assay P-glycoprotein substrates identified in KB-3-1 adenocarcinoma cell line, qHTS therapeutic library screen ChEMBL
HUT78 Antiproliferative assay Antiproliferative activity against human HUT78 cells assessed as reduction in cell viability, IC50=0.378μM 31301565
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=0.01585μM ChEMBL
CEM/C1 Antiproliferative assay Antiproliferative activity against human CEM/C1 cells assessed as reduction in cell viability, IC50=0.03μM 31301565
RPMI8226 Antiproliferative assay Antiproliferative activity against human RPMI8226 cells assessed as reduction in cell viability, IC50=0.538μM 31301565
MM1S Antiproliferative assay Antiproliferative activity against human MM1S cells assessed as reduction in cell viability, IC50=0.032μM 31301565
OVCAR8 Cytotoxicity assay 72 hrs Cytotoxicity against human OVCAR8 cells assessed as reduction in cell viability incubated for 72 hrs by SRB assay, IC50=0.54μM 31301565
MOLT4 Antiproliferative assay Antiproliferative activity against human MOLT4 cells assessed as reduction in cell viability, IC50=0.066μM 31301565
MV4-11 Antiproliferative assay Antiproliferative activity against human MV4-11 cells assessed as reduction in cell viability, IC50=0.635μM 31301565
LNCAP Antiproliferative assay Antiproliferative activity against human LNCAP cells, IC50=0.07μM 31298542
HCT116 Antiproliferative assay 72 hrs Antiproliferative activity against human HCT116 cells after 72 hrs by SRB assay, IC50=0.72μM 31298542
PTEN-null LNCAP Function assay 1 hr Inhibition of Akt in human PTEN-null LNCAP cells assessed as suppression in PRAS40 phosphorylation after 1 hr by ELISA analysis, IC50=0.07563μM 27089211
HCT116 Growth inhibition assay 72 hrs Growth inhibition of human HCT116 cells over-expressing DHODH at 2 times antiproliferative IC50 after 72 hrs in absence of uridine by MTT assay 31301565
U937 Antiproliferative assay Antiproliferative activity against human U937 cells assessed as reduction in cell viability, IC50=0.101μM 31301565
OVCAR8 Antiproliferative assay Antiproliferative activity against human OVCAR8 cells, IC50=0.24μM 31298542
JVM2 Antiproliferative assay Antiproliferative activity against human JVM2 cells assessed as reduction in cell viability, IC50=0.293μM 31301565
HUT78 Antiproliferative assay Antiproliferative activity against human HUT78 cells assessed as reduction in cell viability, IC50=0.378μM 31301565
RPMI8226 Antiproliferative assay Antiproliferative activity against human RPMI8226 cells assessed as reduction in cell viability, IC50=0.538μM 31301565
OVCAR8 Cytotoxicity assay 72 hrs Cytotoxicity against human OVCAR8 cells assessed as reduction in cell viability incubated for 72 hrs by SRB assay, IC50=0.54μM 31301565
MV4-11 Antiproliferative assay Antiproliferative activity against human MV4-11 cells assessed as reduction in cell viability, IC50=0.635μM 31301565
HCT116 Antiproliferative assay 72 hrs Antiproliferative activity against human HCT116 cells after 72 hrs by SRB assay, IC50=0.72μM 31298542
HCT116 Growth inhibition assay 72 hrs Growth inhibition of human HCT116 cells over-expressing DHODH at 2 times antiproliferative IC50 after 72 hrs in absence of uridine by MTT assay 31301565
Click to View More Cell Line Experimental Data

Biological Activity

Description Uprosertib (GSK2141795, GSK795) is a selective, ATP-competitive, and orally bioavailable Akt inhibitor with IC50 of 180 nM, 328 nM, and 38 nM for Akt 1, 2 and 3, respectively. Phase 2.
Targets
Akt3 [1]
(Cell-free assay)		 Akt1 [1]
(Cell-free assay)		 Akt2 [1]
(Cell-free assay)
38 nM 180 nM 328 nM
In vitro
In vitro

Uprosertib inhibits multiple AKT substrate phosphorylation levels, including GSK3β, PRAS40, FOXO and Caspase 9 in both BT474 and LNCaP cells. Uprosertib preferentially inhibits the proliferation of human cancer cells lines with AKT pathway activation. In LNCaP, BT474, A3 and I9.2 cells lines, Uprosertib also causes cell cycle arrest. [2] In both SKOV3 and PEO4 cells, Uprosertib causes growth-arrest as single agent, and enhances induced apoptosis. [3]
Kinase Assay Selectivity profiling experiments
The lysates (5 mg of total protein each) are preincubated with 0 (DMSO control), 2.5 nM, 25 nM, 250 nM, 2.5 μM or 25 μM free compound (GSK690693 or GSK2141795) on an end-over-end shaker for 45 min at 4 °C. Subsequently, lysates are incubated with beads (coupled Akt probe or kinobeads) for 1 h at 4 °C, for both qualitative and quantitative experiments. The beads are washed with 1× CP buffer and collected by centrifugation. Bound proteins are eluted with 2× NuPAGE LDS sample buffer, and eluates are reduced and alkylated by 50 mM dithiothreitol and 55 mM iodoacetamide.
Cell Research Cell lines A panel of 290 cells lines
Concentrations ~30 μM
Incubation Time 3 d
Method

Cell lines are typically grown in RPMI 160 medium containing 10% FBS. Some cell lines are grown in media specified by the vendor. 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.
In Vivo
In vivo

In mice bearing BT474 breast tumor xenografts, Uprosertib (100 mg/kg, p.o.) results 61% tumor growth inhibition. In mice bearing SKOV3 ovarian tumor xenografts, Uprosertib (30 mg/kg, p.o.) results 61% tumor growth inhibition. [2]
Animal Research Animal Models Mice bearing either BT474 or SKOV3 tumors
Dosages 100 mg/kg
Administration p.o.
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT01958112 Terminated
Cervical Cancer
Dana-Farber Cancer Institute|Novartis|National Comprehensive Cancer Network
 October 2013 Phase 2
NCT01941927 Completed
Melanoma
Adil Daud|National Comprehensive Cancer Network|University of California San Francisco
 September 10 2013 Phase 2
NCT01266954 Completed
Solid Tumours
GlaxoSmithKline
 June 1 2010 Phase 1
NCT01138085 Completed
Cancer
GlaxoSmithKline
 May 4 2010 Phase 1

Chemical Information & Solubility

Molecular Weight 429.25 Formula

C18H16Cl2F2N4O2
CAS No. 1047634-65-0 SDF Download Uprosertib (GSK2141795) SDF
Smiles CN1C(=C(C=N1)Cl)C2=C(OC(=C2)C(=O)NC(CC3=CC(=C(C=C3)F)F)CN)Cl
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 85 mg/mL ( (198.01 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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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

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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.

Handling Instructions

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