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| 25mg |
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| 50mg |
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| 100mg |
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Purity: ≥98%
Uprosertib (formerly known as GSK2141795 and GSK795), an analog of GSK2110183, is a potent, orally bioavailable and ATP-competitive Akt inhibitor with IC50 values of 180 nM, 328 nM, and 38 nM for Akt1/Akt2/Akt3, respectively. prosertib is a serine/threonine protein kinase Akt (protein kinase B) inhibitor with potential anti-cancer properties. Uprosertib, an Akt inhibitor, binds to and blocks the activity of Akt, which may inhibit the PI3K/Akt signaling pathway, halt tumor cell growth, and trigger tumor cell apoptosis. The PI3K/Akt signaling pathway is frequently involved in the development of tumors, and aberrant PI3K/Akt signaling may play a role in the development of tumor resistance to a range of antineoplastic agents.
| Targets |
Akt3 (IC50 = 38 nM); Akt1 (IC50 = 180 nM); Akt2 (IC50 = 328 nM); ROCK1 (IC50 = 1570 nM); ROCK2 (IC50 = 1850 nM); CDK7 (IC50 = 2100 nM)
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| ln Vitro |
In both BT474 and LNCaP cells, uprosertib inhibits multiple AKT substrate phosphorylation levels, including GSK3β, PRAS40, FOXO, and Caspase 9. When the AKT pathway is activated in human cancer cell lines, uprosertib preferentially prevents cell proliferation. Uprosertib also results in cell cycle arrest in the cell lines LNCaP, BT474, A3, and I9.2. [2] Uprosertib inhibits growth as a single agent in SKOV3 and PEO4 cells and increases cisplatin-induced apoptosis. [3]
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| ln Vivo |
Uprosertib (100 mg/kg, p.o.) results in a 61% inhibition of tumor growth in mice with BT474 breast tumor xenografts. Uprosertib (30 mg/kg, p.o.) results in a 61% inhibition of tumor growth in mice with SKOV3 ovarian tumor xenografts. [2]
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| Enzyme Assay |
The lysates (5 mg of total protein each) are preincubated for 45 minutes at 4 °C with the following free compounds: DMSO control, 2.5 nM, 25 nM, 250 nM, 2.5 M, or 25 M (GSK690693 or GSK2141795). For both qualitative and quantitative experiments, lysates are then incubated with beads (coupled Akt probe or kinobeads) for 1 h at 4 °C. The beads are centrifuged to separate them after being cleaned with a 1 CP buffer. Using 2 NuPAGE LDS sample buffer, bound proteins are eluted, and the eluates are then reduced and alkylated with 50 mM dithiothreitol and 55 mM iodoacetamide.
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| Cell Assay |
Cell lines are typically grown in 10% FBS-RPMI 160 medium. Some cell lines are grown in media that the vendor specifies. To measure the growth inhibition caused by the compounds at 0–30 M, a 3-day proliferation assay using CellTiter-Glo is carried out. The rate of cell growth is measured in comparison to untreated (DMSO) controls. In the Assay Client application, EC50 values are calculated from inhibition curves using a 4- or 6-parameter fitting algorithm.
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| Animal Protocol |
Mice bearing either BT474 or SKOV3 tumors
100 mg/kg p.o. |
| References |
| Molecular Formula |
C18H16CL2F2N4O2
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| Molecular Weight |
429.25
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| Exact Mass |
428.06184
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| Elemental Analysis |
C, 50.37; H, 3.76; Cl, 16.52; F, 8.85; N, 13.05; O, 7.45
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| CAS # |
1047634-65-0
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| Related CAS # |
Uprosertib hydrochloride;1047635-80-2
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| Appearance |
White to off-white solid powder
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| SMILES |
CN1C(=C(C=N1)Cl)C2=C(OC(=C2)C(=O)N[C@@H](CC3=CC(=C(C=C3)F)F)CN)Cl
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| InChi Key |
AXTAPYRUEKNRBA-JTQLQIEISA-N
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| InChi Code |
InChI=1S/C18H16Cl2F2N4O2/c1-26-16(12(19)8-24-26)11-6-15(28-17(11)20)18(27)25-10(7-23)4-9-2-3-13(21)14(22)5-9/h2-3,5-6,8,10H,4,7,23H2,1H3,(H,25,27)/t10-/m0/s1
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| Chemical Name |
N-[(2S)-1-amino-3-(3,4-difluorophenyl)propan-2-yl]-5-chloro-4-(4-chloro-2-methylpyrazol-3-yl)furan-2-carboxamide
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.82 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2.5 mg/mL (5.82 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.82 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3296 mL | 11.6482 mL | 23.2964 mL | |
| 5 mM | 0.4659 mL | 2.3296 mL | 4.6593 mL | |
| 10 mM | 0.2330 mL | 1.1648 mL | 2.3296 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Status | Interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT01902173 | Active Recruiting |
Drug: Uprosertib Procedure: Biopsy |
Unresectable Melanoma Metastatic Melanoma |
National Cancer Institute (NCI) |
July 19, 2013 | Phase 1 Phase 2 |
| NCT01989598 | Completed | Drug: Uprosertib Drug: Trametinib |
Recurrent Plasma Cell Myeloma Refractory Plasma Cell Myeloma |
National Cancer Institute (NCI) |
October 30, 2013 | Phase 2 |
| NCT01979523 | Completed | Drug: Trametinib Drug: Uprosertib |
Recurrent Uveal Melanoma | National Cancer Institute (NCI) |
October 23, 2013 | Phase 2 |
| NCT02093546 | Completed | Procedure: Biospecimen Collection |
Alzheimer's Disease | Recurrent Endometrial Carcinoma |
August 13, 2004 |
Effect of the small-molecule AMPK activator 991 on activity of a panel of 139 protein kinases.Am J Physiol Endocrinol Metab.2016 Oct 1;311(4):E706-E719. |
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991 treatment enhances AMPK activity induced by 5-aminoimidazole-4-carboxamide riboside (AICAR) or C13 in hepatocytes.Am J Physiol Endocrinol Metab.2016 Oct 1;311(4):E706-E719. |
991 activator binding to AMPK.Nat Commun.2013;4:3017. doi: 10.1038/ncomms4017. |
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