Uprosertib (GSK2141795)

Catalog No.S7492 Batch:S749201

Print

Technical Data

Formula

C18H16Cl2F2N4O2
Molecular Weight 429.25 CAS No. 1047634-65-0
Solubility (25°C)* In vitro DMSO 93 mg/mL (216.65 mM)
Ethanol 93 mg/mL (216.65 mM)
Water Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

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 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 cisplatin-induced apoptosis. [3]
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]

Protocol (from reference)

Kinase Assay:[1]
  • 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 Assay:[2]
  • 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.
Animal Study:[2]
  • Animal Models

    Mice bearing either BT474 or SKOV3 tumors

  • Dosages

    100 mg/kg

  • Administration

    p.o.

Customer Product Validation

Data from [Data independently produced by , , The Ohio State University, 2015]

Selleck's Uprosertib (GSK2141795) has been cited by 12 publications

MAPK4 promotes triple negative breast cancer growth and reduces tumor sensitivity to PI3K blockade [ Nat Commun, 2022, 13(1):245] PubMed: 35017531
PGE2 activates EP4 in subchondral bone osteoclasts to regulate osteoarthritis [ Bone Res, 2022, 10(1):27] PubMed: 35260562
Reversal of IKZF1-induced glucocorticoid resistance by dual targeting of AKT and ERK signaling pathways [ Front Oncol, 2022, 12:905665] PubMed: 36119546
FOXO1 Alleviates Liver Ischemia-reperfusion Injury by Regulating the Th17/Treg Ratio through the AKT/Stat3/FOXO1 Pathway [ J Clin Transl Hepatol, 2022, 10(6):1138-1147] PubMed: 36381102
MAPK6-AKT signaling promotes tumor growth and resistance to mTOR kinase blockade [ Sci Adv, 2021, 7(46):eabi6439] PubMed: 34767444
Lactic acidosis induces resistance to the pan-Akt inhibitor uprosertib in colon cancer cells. [ Br J Cancer, 2020, 10.1038/s41416-020-0777-y] PubMed: 32152504
The PI3K/mTOR dual inhibitor GSK458 potently impedes ovarian cancer tumorigenesis and metastasis. [ Cell Oncol (Dordr), 2020, 8] PubMed: 32382996
β1 integrin, ILK and mTOR regulate collagen synthesis in mechanically loaded tendon cells [ Sci Rep, 2020, 10(1):12644] PubMed: 32724089
MSC-secreted TGF-β regulates lipopolysaccharide-stimulated macrophage M2-like polarization via the Akt/FoxO1 pathway. [ Stem Cell Res Ther, 2019, 10(1):345] PubMed: 31771622
PI3K/AKT inhibitors aggravate death receptor-mediated hepatocyte apoptosis and liver injury. [ Toxicol Appl Pharmacol, 2019, 381:114729] PubMed: 31445927

RETURN POLICY
Selleck Chemical’s Unconditional Return Policy ensures a smooth online shopping experience for our customers. If you are in any way unsatisfied with your purchase, you may return any item(s) within 7 days of receiving it. In the event of product quality issues, either protocol related or product related problems, you may return any item(s) within 365 days from the original purchase date. Please follow the instructions below when returning products.

SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.