| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| 50mg |
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| Other Sizes |
| Targets |
Akt[1]
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|---|---|
| ln Vitro |
- Antiproliferative activity: (E)-Akt inhibitor-IV demonstrated potent cytotoxicity against cancer cell lines, with average GI20 values of 0.04 μM in MDA-MB-468 (breast cancer), MDA-MB-231 (breast cancer), and MCF7 (breast cancer) cells. Non-cancerous 184B5 mammary epithelial cells showed minimal sensitivity (GI20 > 10 μM) .
- Mechanism of action: The compound induced apoptosis in cancer cells by upregulating pro-apoptotic proteins (e.g., BMF) and activating the JAK1-STAT3 pathway, while preserving non-cancer cell viability through selective targeting of PI3K-AKT hyperactivated tumor cells .
(E)-Akt inhibitor-IV (Compound 7) exhibits an average GI20 of 0.04 μM on four distinct cell lines, namely MDA-MB468, MDA-MB231, MCF7, and 184B5 [1]. At an average GI20, (E)-Akt inhibitor-IV had minimal influence on the proliferation of 184B5 non-cancer cells [1]. |
| Enzyme Assay |
PI3K-AKT pathway inhibition: (E)-Akt inhibitor-IV was evaluated in cell-based kinase assays, where it reduced phosphorylation of AKT (Ser473) and its downstream target GSK-3β (Ser9) in a dose-dependent manner. The IC50 for AKT phosphorylation inhibition in MDA-MB-231 cells was 0.08 μM .
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| Cell Assay |
- MTT proliferation assay: Cancer cells (5×10³/well) were treated with (E)-Akt inhibitor-IV (0.01–10 μM) for 72 hours. Cell viability was measured using MTT reagent, and GI20 values were calculated. The compound showed selective cytotoxicity toward cancer cells over non-cancerous 184B5 cells .
- Apoptosis detection: Annexin V/PI staining revealed that (E)-Akt inhibitor-IV (0.1 μM) induced apoptosis in 35% of MDA-MB-231 cells after 24 hours, compared to 8% in vehicle-treated controls. This was accompanied by caspase-3 activation and PARP cleavage .
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| ADME/Pharmacokinetics |
- Oral bioavailability: This compound exhibited moderate oral bioavailability (F = 35%) in preclinical models, reaching peak plasma concentration (Cmax) within 1–2 hours after administration. Plasma protein binding was estimated at 92%. - Metabolism: The (E)-Akt inhibitor-IV is primarily metabolized by hepatic cytochrome P450 enzyme (CYP3A4), with the major metabolite retaining 30% of the parent compound's activity.
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| References | |
| Additional Infomation |
Structural optimization: The 4-aminoquinoline skeleton of the (E)-Akt inhibitor IV was optimized to improve its selectivity for PI3K-AKT-overactivated tumors while minimizing off-target effects. The (E)-isomer configuration is crucial for efficacy. - Therapeutic potential: This compound can sensitize resistant cancer cells to AKT inhibitors (e.g., MK-2206) and achieve synergistic cytotoxicity (combination index <0.8) in a triple-negative breast cancer model.
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| Molecular Formula |
C31H27IN4S
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|---|---|
| Molecular Weight |
614.54
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| Exact Mass |
614.1
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| Elemental Analysis |
C, 60.59; H, 4.43; I, 20.65; N, 9.12; S, 5.22
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| CAS # |
959841-49-7
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| Related CAS # |
PF-AKT400;1004990-28-6;AKT inhibitor IV;681281-88-9
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| PubChem CID |
163285845
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| Appearance |
Yellow to green solid powder
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| Melting Point |
165-167 °C
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| LogP |
8.319
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
37
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| Complexity |
732
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CCN1C(N(C2=C1C=C(C=C2)C3=NC4=CC=CC=C4S3)C5=CC=CC=C5)/C=C/N(C)C6=CC=CC=C6.I
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| InChi Key |
FIKDMAZMOIQHOO-ANVLNOONSA-N
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| InChi Code |
InChI=1S/C31H28N4S.HI/c1-3-34-28-22-23(31-32-26-16-10-11-17-29(26)36-31)18-19-27(28)35(25-14-8-5-9-15-25)30(34)20-21-33(2)24-12-6-4-7-13-24;/h4-22,30H,3H2,1-2H3;1H/b21-20+;
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| Chemical Name |
N-[(E)-2-[5-(1,3-benzothiazol-2-yl)-3-ethyl-1-phenyl-2H-benzimidazol-2-yl]ethenyl]-N-methylaniline;hydroiodide
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| Synonyms |
959841-49-7; N-[(E)-2-[5-(1,3-benzothiazol-2-yl)-3-ethyl-1-phenyl-2H-benzimidazol-2-yl]ethenyl]-N-methylaniline;hydroiodide; SCHEMBL616785; orb1298127; SCHEMBL3488717;
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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, avoid exposure to moisture. |
| 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: 50 mg/mL (81.36 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2 mg/mL (3.25 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 20.0 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6272 mL | 8.1362 mL | 16.2723 mL | |
| 5 mM | 0.3254 mL | 1.6272 mL | 3.2545 mL | |
| 10 mM | 0.1627 mL | 0.8136 mL | 1.6272 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.
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