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Purity: ≥98%
GSK2110183, an analog of Afuresertib, 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. GSK2110183 is a protein kinase B (Akt) inhibitor with potential anticancer properties. 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 |
Akt1 (Ki = 0.08 nM); Akt2 (Ki = 2 nM); Akt3 (Ki = 2.6 nM)
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|---|---|
| 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 M). In response to afuresertib, 21% of tested solid tumor cell lines have an EC50 1 M. [1]
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| ln Vivo |
Afuresertib (p. o.) doses of 10, 30, or 100 mg/kg per day cause 8, 37, or 61% TGI in mice with BT474 breast tumor xenografts. Treatments with 10, 30, and 100 mg/kg of afuresertib result in 23, 37, and 97% TGI, respectively, in mice with SKOV3 ovarian tumor xenografts. [1]
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| Enzyme Assay |
Afuresertib (p.o.) is dosed at 10, 30, or 100 mg/kg per day to mice with BT474 breast tumor xenografts, resulting in 8, 37, or 61% TGI, respectively. 10, 30, and 100 mg/kg of afuresertib are administered to mice containing ovarian tumor xenografts bearing the SKOV3 gene, and these doses produce TGI of 23, 37, and 97%, respectively. [1] With the aid of a filter binding assay and progress curve analysis, the inhibitor's true potency (Ki*) is first ascertained at low enzyme concentrations (0.1 nM AKT1, 0.7 nM AKT2, and 0.2 nM AKT3). 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 [γ33P] ATP.
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| Cell Assay |
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 |
Female athymic nude and SCID mice bearing SKOV3 or BT474 tumors
100 mg/kg p.o. |
| References |
| Molecular Formula |
C₁₈H₁₆CL₂F₂N₄OS
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|---|---|
| Molecular Weight |
445.31
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| Exact Mass |
444.039
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| Elemental Analysis |
C, 48.55; H, 3.62; Cl, 15.92; F, 8.53; N, 12.58; O, 3.59; S, 7.20
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| CAS # |
1047634-63-8
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| Related CAS # |
GSK2110183 analog 1 hydrochloride;2070009-64-0
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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(=C(C=C3)F)F)CN)Cl
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| InChi Key |
AHDFWNJLFALBJP-JTQLQIEISA-N
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| InChi Code |
InChI=1S/C18H16Cl2F2N4OS/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)thiophene-2-carboxamide
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| Synonyms |
Afuresertib-F; Afuresertib-F free base; GSK-2110183-analog; GSK 2110183-analog; GSK2110183-analog
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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) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2456 mL | 11.2281 mL | 22.4563 mL | |
| 5 mM | 0.4491 mL | 2.2456 mL | 4.4913 mL | |
| 10 mM | 0.2246 mL | 1.1228 mL | 2.2456 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 |
| NCT01531894 | Completed | Drug: GSK2110183 (afuresertib) |
Cancer | Novartis Pharmaceuticals | February 8, 2012 | Phase 2 |
| NCT01428492 | Completed | Drug: GSK2110183 Drug: Bortezomib |
Multiple Myeloma | Novartis | December 2011 | Phase 1 |
| NCT01476137 | Completed | Drug: GSK1120212 Drug: GSK2110183 |
Cancer | GlaxoSmithKline | October 26, 2011 | Phase 1 |
| NCT00881946 | Completed | Drug: GSK21110183 | Hematologic Malignancies | Accenture | July 2009 | Phase 1 Phase 2 |
| NCT01395004 | Completed | Drug: GSK2110183 | Langerhans Cell Histiocytosis | GlaxoSmithKline | November 2011 | Phase 2 |
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