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Purity: ≥98%
Akti-1/2 (known also as AKT inhibitor VIII), a quinoxaline-based compound, is a novel, potent, selective, cell-permeable and allosteric inhibitor of Akt1/2 with potential anticancer activity. It has an IC50 of 58 nM for Akt1 and 210 nM for Akt2, respectively, and is about 36-fold more selective for Akt1 than Akt3. AKTi-1/2. Akts, PKA, PKC, and SGK lacking the pleckstrin homology (PH) domain did not exhibit any inhibition.
| Targets |
Akt1 (IC50 = 58 nM); Akt2 (IC50 = 210 nM); Akt3 (IC50 = 2119 nM)
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|---|---|
| ln Vitro |
Akti-1/2 inhibits Akt1 and Akt2 with an IC50 of 305 nM and 2086 nM, respectively, in a cell-based IPKA (C33A) assay. Akti-1/2 causes cell apoptosis in HT29, MCF7, and A2780 cells by significantly raising caspase-3 activity. [1]
Akti-1/2 prevents insulin from controlling the expression of PEPCK, G6Pase, and FOXO1 in liver cells. [2] Akti-1/2 also strongly potentiates PAR-1-mediated platelet aggregation by blocking PKB. [3] Akti-1/2 inhibits cell growth in HCC827, NCI-H522, NCI-1651, and PC-9 cells with IC50 values of 4.7 μM, 7.25 μM, and 9.5 μM; when combined with gefitinib, Akti-1/2 results in enhanced inhibition of cell growth and apoptosis. [4] |
| ln Vivo |
Akti-1/2 (50 mg/kg, i.p.) inhibits lung Akt1 and Akt2 phosphorylation in mice at both basal and IGF-stimulated levels.AKT inhibitor VIII (50 mpk, 3 doses, ip, every 90 min) is administered to mice to achieve plasma concentrations of 1.5–2.0 μM. IGF is then administered intravenously to the animals' tail veins to promote Akt phosphorylation. Both basal and IGF-stimulated Akt1 and Akt2 phosphorylation are inhibited by IP Western in mouse lung, but Akt3 phosphorylation is unaffected.
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| Enzyme Assay |
Briefly, a Biomek 2000 Laboratory Automation Workstation in a 96-well format is used to carry out all assays (25.5 μl at 21°C for 30 min). The addition of 10 mM MgAcetate and 5, 20, or 50 μM ATP ([γ-33P]-, 800 cpm/pmol) initiates reactions that contain 5–20 mU purified kinase and substrate protein or peptide.
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| Cell Assay |
Using the 96-hour sulforhodamine B assay (SRB), it is possible to determine how AKTi-1/2 inhibits cell growth. The sigmoidal dose-response (variable slope) equation and non-linear regression analysis are used in GraphPad Prism 6.0 to calculate the drug concentrations that inhibited 50% of cell growth (IC50) for each compound.
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| Animal Protocol |
C57BL/6 J mice
50 mg/kg i.p. |
| References |
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| Additional Infomation |
3-[1-[[4-(7-phenyl-3H-imidazo[4,5-g]quinoxalin-6-yl)phenyl]methyl]-4-piperidinyl]-1H-benzimidazol-2-one is a member of piperidines.
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| Molecular Formula |
C34H29N7O
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|---|---|
| Molecular Weight |
551.6404
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| Exact Mass |
551.243
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| Elemental Analysis |
C, 74.03; H, 5.30; N, 17.77; O, 2.90
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| CAS # |
612847-09-3
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| Related CAS # |
PF-AKT400;1004990-28-6
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| PubChem CID |
135398501
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.4±0.1 g/cm3
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| Melting Point |
242-245ºC (dec.)
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| Index of Refraction |
1.734
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| LogP |
5.1
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
42
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| Complexity |
1270
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C1N([H])C2=C([H])C([H])=C([H])C([H])=C2N1C1([H])C([H])([H])C([H])([H])N(C([H])([H])C2C([H])=C([H])C(C3=C(C4C([H])=C([H])C([H])=C([H])C=4[H])N=C4C([H])=C5C(C([H])=C4N3[H])=NC([H])=N5)=C([H])C=2[H])C([H])([H])C1([H])[H]
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| InChi Key |
BIWGYFZAEWGBAL-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C34H29N7O/c42-34-39-26-8-4-5-9-31(26)41(34)25-14-16-40(17-15-25)20-22-10-12-24(13-11-22)33-32(23-6-2-1-3-7-23)37-29-18-27-28(36-21-35-27)19-30(29)38-33/h1-13,18-19,21,25H,14-17,20H2,(H,35,36)(H,39,42)
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| Chemical Name |
3-[1-[[4-(7-phenyl-3H-imidazo[4,5-g]quinoxalin-6-yl)phenyl]methyl]piperidin-4-yl]-1H-benzimidazol-2-one
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| Synonyms |
Sigma-A6730; AKT inhibitor VIII; AKT inhibitor-8; AKT-inhibitor-VIII; AKT-inhibitor-8; Akt-I 1,2; Akti-1/2
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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) |
DMSO: ~22 mg/mL (~39.9 mM)
Water: <1 mg/mL Ethanol: <1 mg/mL |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2 mg/mL (3.63 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 20.0 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 mg/mL (3.63 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 20.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8128 mL | 9.0639 mL | 18.1278 mL | |
| 5 mM | 0.3626 mL | 1.8128 mL | 3.6256 mL | |
| 10 mM | 0.1813 mL | 0.9064 mL | 1.8128 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 |
| NCT00897663 | Completed | Genetic: microarray analysis Genetic: gene expression analysis |
Brain and Central Nervous System Tumors |
Alliance for Clinical Trials in Oncology |
November 2006 | Phase 3 |
| NCT00671970 | Completed | Drug: Bevacizumab and Erlotinib |
Glioblastoma Gliosarcoma |
Duke University | February 2007 | Phase 2 |
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