| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| Other Sizes |
|
Purity: ≥98%
Afuresertib (also named as GSK2110183C) is a potent, orally bioavailable and ATP-competitive Akt inhibitor with potential anticancer activity. With Kis of 0.08 nM, 2 nM, and 2.6 nM, respectively, it inhibits Akt1, Akt2, and Akt3. Afuresertib may have anti-cancer effects because it inhibits the serine/threonine protein kinase Akt (protein kinase B). The PI3K/Akt signaling pathway, tumor cell proliferation, and 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 aberrant PI3K/Akt signaling may play a role in the development of tumor resistance to various antineoplastic agents.
| Targets |
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); PKCθ (IC50 = 510 nM); ROCK (IC50 = 100 nM)
|
|---|---|
| ln Vitro |
Afuresertib inhibits the kinase activity of the E17K AKT1 mutant protein with EC50 of 0.2 nM. Afuresertib has a concentration-dependent impact on the phosphorylation levels of several AKT substrates, including GSK3b, PRAS40, FOXO, and Caspase 9. Afuresertib has an overall sensitivity of 65% for hematological cell lines (EC50 < 1 μM). In response to afuresertib, 21% of tested solid tumor cell lines have an EC50 < 1 μM. [1]
|
| ln Vivo |
Afuresertib (p.o.) is dosed to mice with BT474 breast tumor xenografts at 10, 30, or 100 mg/kg per day, resulting in 8, 37, or 61% TGI, respectively. Treatment with 10, 30, and 100 mg/kg afuresertib causes 23, 37, and 97% TGI in mice with SKOV3 ovarian tumor xenografts, respectively. [1]
|
| Enzyme Assay |
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, an enzyme and an inhibitor pre-mix are incubated for 1 hour before being added to a GSK peptide (Ac-KKGGRARTSS-FAEPG-amide) and [33P] ATP. In a phospho-cellulose filter plate, the radio-labeled AKT peptide product is collected after the reaction has been shut down for two hours. By using the Sox-AKT-tide substrate (Ac-ARKRERAYSF-d-Pro-Sox-Gly-NH2), progress curve analysis continuously monitors the fluorescence of the product as it is. formed.
|
| Cell Assay |
A 3-day proliferation assay using CellTiter-Glo is performed to measure the growth inhibition by the compounds at 0-30 μM. 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.
|
| Animal Protocol |
Female athymic nude and SCID mice bearing SKOV3 or BT474 tumors
100 mg/kg p.o. |
| References |
| Molecular Formula |
C18H17CL2FN4OS
|
|---|---|
| Molecular Weight |
427.32
|
| Exact Mass |
426.0784
|
| Elemental Analysis |
C, 50.59; H, 4.01; Cl, 16.59; F, 4.45; N, 13.11; O, 3.74; S, 7.50
|
| CAS # |
1047644-62-1
|
| Related CAS # |
Afuresertib hydrochloride;1047645-82-8
|
| Appearance |
Solid powder
|
| SMILES |
CN1C(=C(C=N1)Cl)C2=C(SC(=C2)C(=O)N[C@@H](CC3=CC(=CC=C3)F)CN)Cl
|
| InChi Key |
AFJRDFWMXUECEW-LBPRGKRZSA-N
|
| InChi Code |
InChI=1S/C18H17Cl2FN4OS/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)/t12-/m0/s1
|
| Chemical Name |
N-[(2S)-1-amino-3-(3-fluorophenyl)propan-2-yl]-5-chloro-4-(4-chloro-2-methylpyrazol-3-yl)thiophene-2-carboxamide
|
| Synonyms |
Afuresertib free base; GSK 2110183; GSK2110183; GSK-2110183; GSK 2110183C; GSK2110183C; GSK2110183C
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
|
|||
|---|---|---|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.85 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 (5.85 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 (5.85 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 | 2.3402 mL | 11.7008 mL | 23.4017 mL | |
| 5 mM | 0.4680 mL | 2.3402 mL | 4.6803 mL | |
| 10 mM | 0.2340 mL | 1.1701 mL | 2.3402 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 |
| NCT05383482 | Recruiting | Drug: Afuresertib Drug: Docetaxel |
Solid Tumor NSCLC |
Laekna Limited | June 30, 2022 | Phase 1 Phase 2 |
| NCT05390710 | Recruiting | Drug: Nab-paclitaxel | Solid Tumor | Laekna Limited | June 12, 2021 | Phase 1 Phase 2 |
| NCT04851613 | Active Recruiting |
Drug: Afuresertib | Breast Cancer | Laekna LLC | February 18, 2022 | Phase 1 |
| NCT04060394 | Active Recruiting |
Drug: Phase I and Phase II:LAE001/prednisone + afuresertib |
Metastatic Castration- resistant Prostate Cancer |
Laekna Limited | September 13, 2019 | Phase 1 Phase 2 |
| NCT04374630 | Active Recruiting |
Drug: Paclitaxel Drug: Afuresertib |
Platinum-resistant Ovarian Cancer |
Laekna Limited | June 9, 2020 | Phase 2 |
Effect of GSK2110183 on AKT signaling and growth inhibition in human cancer cell lines. PLoS One, 2014, 9(6):e100880. |
The impact of GSK2110183 and GSK2141795 on glucose homeostasis in vivo. |
Combination anti-tumor effect of AKT and MEK inhibitors in mouse models of pancreatic cancer. |
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA
