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| 2mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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Purity: ≥98%
Afuresertib HCl (also named as GSK2110183 HCl) is a potent, orally bioavailable and ATP-competitive Akt inhibitor with Ki of 0.08 nM, 2 nM, and 2.6 nM for Akt1, Akt2, and Akt3, respectively. Afuresertib is a protein kinase B (Akt) serine/threonine inhibitor with potential anti-cancer properties. The PI3K/Akt signaling pathway, tumor cell proliferation, and induction of tumor cell apoptosis may all be inhibited as a result of the Akt inhibitor GSK2110183's binding to and inhibition of Akt activity. The PI3K/Akt signaling pathway is frequently involved in the development of tumors, and dysregulated PI3K/Akt signaling may be a factor in the tumors' resistance to a number of different anti-cancer drugs.
| Targets |
Akt1 (Ki = 0.08 nM); Akt2 (Ki = 2 nM); Akt3 (Ki = 2.6 nM); Akt1 E17K mutant (IC50 = 0.2 nM); PKCη (IC50 = 210 nM); PKC-βI (IC50 = 430 nM); ROCK (IC50 = 100 nM); PKCθ (IC50 = 510 nM)
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| ln Vitro |
Afuresertib (GSK 2110183) exhibits favorable tumor-suppressive effects on malignant pleural mesothelioma (MPM) cells.Afuresertib significantly raises the activity of caspase-3 and caspase-7 as well as the proportion of apoptotic cells in ACC-MESO-4 and MSTO-211H cells. The cell cycle is strongly stopped by afuresertib in the G1 phase. Afuresertib increases the expression of p21WAF1/CIP1 and decreases the phosphorylation of Akt substrates, such as GSK-3 and FOXO family proteins, according to Western blotting analysis. By stimulating FOXO activity, afuresertib-induced p21 expression encourages G1 phase arrest. Afuresertib significantly increases the cytotoxicity that cisplatin causes. Afuresertib alters the expression of the genes MYC and E2F1, which are related to the fibroblast core serum response[1].
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| ln Vivo |
GSK2110183 is administered orally to mice bearing BT474 breast tumor xenografts at doses of 10, 30, or 100 mg/kg every day for 21 days, resulting in 8, 37, or 61% TGI, respectively. Mice tolerated GSK2110183 well; after 5 days of dosing, there was a 1-3% loss of body weight, which recovered throughout the course of the study. To further demonstrate the effectiveness of the compound, other tumor xenograft models with activated Akt pathways are investigated. Mice given GSK2110183 at doses of 10, 30, and 100 mg/kg develop SKOV3 xenografts with TGIs of 23, 37, and 97%, respectively[2].
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| Enzyme Assay |
MPM cells are plated in 96-well plates at a cell density of 2.5 103 per well, and then they are left to grow for 24 hours at 37°C. Following that, the cells are incubated for 72 hours in a medium containing the Akt inhibitors at the indicated concentrations (e.g., Afuresertib; 50, 20, 10, 5, 2, 1, 0.5, 0.2, 0.1, and 0.01 M). The cells are then incubated for 4 hours with MTT solution added to each well. The cells are then given an overnight incubation in lysis buffer (10% SDS in 0.01 mol/L hydrogen chloride). Absorbance is measured at 550 nm using SpectraMAX M5 spectrophotometer[1].
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| 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
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| Animal Protocol |
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| References |
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| Molecular Formula |
C₁₈H₁₈CL₃FN₄OS
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| Molecular Weight |
463.78
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| Elemental Analysis |
C, 46.62; H, 3.91; Cl, 22.93; F, 4.10; N, 12.08; O, 3.45; S, 6.91
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| CAS # |
1047645-82-8
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| Related CAS # |
Afuresertib;1047644-62-1
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| Appearance |
Solid powder
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| SMILES |
CN1C(=C(C=N1)Cl)C2=C(SC(=C2)C(=O)N[C@@H](CC3=CC(=CC=C3)F)CN)Cl.Cl
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| InChi Key |
YFQJOPFTGMHYNV-YDALLXLXSA-N
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| InChi Code |
InChI=1S/C18H17Cl2FN4OS.ClH/c1-25-16(14(19)9-23-25)13-7-15(27-17(13)20)18(26)24-12(8-22)6-10-3-2-4-11(21)5-10;/h2-5,7,9,12H,6,8,22H2,1H3,(H,24,26);1H/t12-;/m0./s
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| Chemical Name |
N-[(2S)-1-amino-3-(3-fluorophenyl)propan-2-yl]-5-chloro-4-(4-chloro-2-methylpyrazol-3-yl)thiophene-2-carboxamide;hydrochloride
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| Synonyms |
GSK2110183; GSK 2110183; GSK-2110183; GSK2110183B; GSK2110183B; GSK 2110183B; Afuresertib HCl; Afuresertib hydrochloride; Afuresertib
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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 |
| 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 (5.39 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 (5.39 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 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 (5.39 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 | 2.1562 mL | 10.7810 mL | 21.5619 mL | |
| 5 mM | 0.4312 mL | 2.1562 mL | 4.3124 mL | |
| 10 mM | 0.2156 mL | 1.0781 mL | 2.1562 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 |
| NCT04374630 | Active Recruiting |
Drug: Paclitaxel Drug: Afuresertib |
Platinum-resistant Ovarian Cancer |
Laekna Limited | June 9, 2020 | Phase 2 |
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Products are for research use only; We do not sell to patients
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