| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg | |||
| 250mg | |||
| Other Sizes |
Purity: ≥98%
| Targets |
AKT-I-1 primarily targets the serine/threonine-protein kinase Akt1 with a half-maximal inhibitory concentration (IC50) of 4.6 μM. The compound exhibits high selectivity over other Akt isoforms, with IC50 values greater than 250 μM for both Akt2 and Akt3. Furthermore, its inhibitory potency against other AGC kinase family members, such as serum/glucocorticoid-regulated kinase (SGK), is significantly weaker than that against Akt1.
|
|---|---|
| ln Vitro |
At the cellular level, AKT-I-1 effectively penetrates cell membranes and inhibits the phosphorylation of Akt at Thr308 and Ser473, thereby reducing its kinase activity. This further leads to the blockade of downstream substrate phosphorylation, such as PRAS40 and ribosomal protein S6. Additionally, AKT-I-1 induces tumor cell cycle arrest by upregulating the expression of cyclin-dependent kinase inhibitors p21 and p27, and enhances TRAIL-induced apoptosis in LNCaP prostate cancer cells.
|
| ln Vivo |
In a BT474c breast adenocarcinoma xenograft mouse model, continuous daily oral administration of AKT-I-1 at doses of 100 mg/kg and 200 mg/kg resulted in dose-dependent inhibition of tumor growth. Notably, at the 200 mg/kg dose, a significant tumor growth inhibition effect was observed. Its in vivo efficacy correlates with its ability to inhibit the phosphorylation of AKT (Ser473) and its downstream substrate GSK3β.
|
| Enzyme Assay |
The in vitro kinase activity of AKT-I-1 is typically measured using commercial kits (e.g., radioactive or non-radioactive methods). In a representative non-radioactive assay, the procedure involves incubating recombinant activated Akt1 kinase, a specific biotinylated peptide substrate, and varying concentrations of AKT-I-1 in a reaction buffer containing ATP. After terminating the reaction, the phosphorylation level of the substrate is detected using specific antibodies. The half-maximal inhibitory concentration (IC50) is then calculated to evaluate its inhibitory potency. Selectivity against Akt2 and Akt3 is assessed using the same experimental setup.
|
| Cell Assay |
In vitro cellular activity of AKT-I-1 is often assessed using its targeted cancer cell line models, such as LNCaP prostate cancer cells. The protocol involves seeding cells in culture plates. After adherence, cells are treated with a gradient concentration of AKT-I-1 for a defined period (e.g., 24-72 hours). Following treatment, cell lysates are collected, and the phosphorylation levels of Akt and its downstream signaling molecules (e.g., GSK3β, PRAS40) are detected via Western blotting. Concurrently, cell viability is evaluated using CCK-8 or MTT assays, and the apoptosis rate is analyzed by flow cytometry using Annexin V/PI staining.
|
| Animal Protocol |
The in vivo anti-tumor activity of AKT-I-1 is typically evaluated in xenograft mouse models. The procedure involves subcutaneously implanting tumor cells (e.g., BT474c) into nude mice. Once tumors reach a predetermined size (e.g., approximately 100-200 mm³), the tumor-bearing mice are randomized into treatment and control groups. The treatment groups receive daily doses of AKT-I-1 (e.g., 100 or 200 mg/kg) via oral gavage or intraperitoneal injection, while the control group receives vehicle. During the treatment period, tumor volumes and body weights are measured and recorded every 2-3 days. At the end of the experiment, mice are sacrificed, and tumors are excised and weighed to calculate the tumor growth inhibition rate. Tumor tissues are also collected for Western blotting to validate target inhibition (e.g., p-AKT, p-GSK3β).
|
| ADME/Pharmacokinetics |
Detailed and systematic reports on the pharmacokinetic (PK) properties of AKT-I-1 itself are currently lacking in the available literature. However, a structural analog, Akt1 and Akt2-IN-1, has demonstrated favorable pharmacokinetics in rats, characterized by low clearance (4.6 mL/min/kg) and a long half-life (3.8 hours), suggesting that AKT-I-1 may also possess advantageous in vivo metabolic properties.
|
| Toxicity/Toxicokinetics |
Based on current research data, AKT-I-1 and related Akt inhibitors have shown a favorable safety profile. In non-cytotoxicity assessments, no obvious adverse effects were observed even at concentrations as high as 100 µM. Furthermore, studies in specific cell and animal models have not reported significant teratogenicity, hepatotoxicity, or cardiotoxicity. These data preliminarily indicate that AKT-I-1 has relatively low off-target toxicity within its effective target-inhibiting concentration range.
|
| References |
: Yamaji M, Ota A, Wahiduzzaman M, Karnan S, Hyodo T, Konishi H, Tsuzuki S, Hosokawa Y, Haniuda M. Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. Cancer Med. 2017 Nov;6(11):2646-2659. doi: 10.1002/cam4.1179. Epub 2017 Sep 27. PubMed PMID: 28960945; PubMed Central PMCID: PMC5673922.
|
| Molecular Formula |
C22H30N6
|
|---|---|
| Molecular Weight |
378.52
|
| Exact Mass |
378.253
|
| CAS # |
473382-39-7
|
| Related CAS # |
473382-39-7;
|
| PubChem CID |
10271028
|
| Appearance |
Typically exists as solid at room temperature
|
| Density |
1.2±0.1 g/cm3
|
| Index of Refraction |
1.642
|
| LogP |
4.01
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
5
|
| Rotatable Bond Count |
7
|
| Heavy Atom Count |
28
|
| Complexity |
499
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
CC(C)(CN=C1C(=CC2=NN=C(C3=CC=CC=C3)N2N1)C4CCC4)CN(C)C
|
| InChi Key |
FKCXKEHHZXEWGP-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C22H30N6/c1-22(2,15-27(3)4)14-23-20-18(16-11-8-12-16)13-19-24-25-21(28(19)26-20)17-9-6-5-7-10-17/h5-7,9-10,13,16H,8,11-12,14-15H2,1-4H3,(H,23,26)
|
| Chemical Name |
N-(7-Cyclobutyl-3-phenyl-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)-N',N',2,2-tetramethylpropane-1,3-diamine
|
| Synonyms |
AKT-I-1 AKT I 1 AKTI1
|
| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
|
|---|---|
| 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 | 2.6419 mL | 13.2093 mL | 26.4187 mL | |
| 5 mM | 0.5284 mL | 2.6419 mL | 5.2837 mL | |
| 10 mM | 0.2642 mL | 1.3209 mL | 2.6419 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA