| Size | Price | Stock | Qty |
|---|---|---|---|
| 10mg |
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| Other Sizes |
| Targets |
Akt1 4.0 nM (IC50) Akt2 97.5 nM (IC50) Akt3 28 nM (IC50) PKA 11 nM (IC50) PKCη 629 nM (IC50) ROCK1 354 nM (IC50) RSK1 756 nM (IC50) p70S6K 229 nM (IC50)
Hu7691 free base targets the serine/threonine kinase Akt (also known as protein kinase B), a key component of the PI3K/Akt signaling pathway that regulates cell proliferation, survival, and metabolism. It is a selective Akt inhibitor with IC50s of 4.0 nM for Akt1, 97.5 nM for Akt2, and 28 nM for Akt3. By inhibiting Akt activity, Hu7691 free base disrupts downstream signaling pathways, leading to anti-proliferative effects and induction of differentiation in neuroblastoma cells. |
|---|---|
| ln Vitro |
Against the majority of the kinases in the four families (AGC, TK, TKL, Lipid/Atypical; PKA, IC50=11 nM; PKCη, IC50=629 nM; ROCK1, IC50=354 nM; RSK1, IC50 =756 nM; P70S6K, IC50=229 nM; SGK, IC50=1009 nM), Hu7691 free base exhibits minimal inhibitions[1]. Hu7691 free base (2.25–36 μM; 24 hours) effectively lowers the level of Akt (S473) phosphorylation[1]. Hu7691 free base (10, 20, 30, 40 μM; for 72 h) has an IC50 value of 15.2 μM, which indicates modest toxicity against HaCaT cells[1]. With an IC50 range of 0.6-27 μM, Hu7691 free base significantly inhibits the growth of 18 different types of human tumor cells (U87-MG, U251, A549, HepG2, HT-29, KHOS, MDA-MB-231, PC3, SKOV3, and so forth) originating from diverse tissues. Hu7691 free base exhibits minimal antiproliferation activity (IC50 values of 5.4 and 16.1 μM, respectively) against HPDE6-C7 and HL7702 normal cells[1].
In vitro, Hu7691 free base demonstrates potent inhibition of Akt1 (IC50 = 4.0 nM), Akt2 (IC50 = 97.5 nM), and Akt3 (IC50 = 28 nM). It has anti-proliferative and neurogenic effects on a variety of neuroblastoma cell lines. The compound significantly inhibits the growth of 18 kinds of human tumor cells derived from different tissues, including U87-MG, U251, A549, HepG2, HT-29, MDA-MB-231, and PC3. These in vitro activities support its potential as an anticancer agent. |
| ln Vivo |
For 22 days, Hu7691 free base (12.5–50 mg/kg/day; ir) exhibits dose-dependent suppression of tumor growth[1]. In rats, Hu7691 free base (15 mg/kg; oral) exhibits an AUC of 2820.64 ng/mL·h, a Cmax of 171.17 ng/mL, and a T1/2 of 8.68 hours[1]. In rats, Hu7691 free base (2 mg/kg; intravenous) exhibits an AUC of 532.87 ng/mL·h, a Cmax of 207.52 ng/mL, and a T1/2 of 6.24 hours[1]. In a beagle dog (male, 40 weeks old, 8–10 kg), Hu7691 free base (20 mg/kg; oral) had an AUC of 36303 ng/mL·h, a T1/2 of 16.7 hours, and a Cmax of 905.65 ng/mL[1].
In vivo, Hu7691 free base inhibits tumor growth and enables decrease of cutaneous toxicity in mice. As an orally active compound, it can be administered via oral gavage. These results support its potential for treating cancers where Akt is dysregulated. The compound's ability to decrease cutaneous toxicity suggests a favorable safety profile compared to other Akt inhibitors. However, specific published in vivo protocols are not detailed in the available literature. |
| Enzyme Assay |
The in vitro Akt inhibition assay for Hu7691 free base uses recombinant Akt1, Akt2, and Akt3 enzymes and a peptide substrate. Kinase activity is measured using radioactive or luminescent detection methods, and IC50 values are calculated from dose-response curves. Anti-proliferative activity is assessed in various cancer cell lines using standard cell viability assays such as MTT or CellTiter-Glo. Neurogenic effects are evaluated in neuroblastoma cell lines.
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| Cell Assay |
Western Blot Analysis[1]
Cell Types: HaCaT cells Tested Concentrations: 2.25, 4.5, 9, 18, 36 μM Incubation Duration: 24 hrs (hours) Experimental Results: Induced effective decrease of the phosphorylation level of Akt (S473). Cellular assays for Hu7691 free base are conducted in neuroblastoma cell lines and various cancer cell lines including U87-MG, U251, A549, HepG2, HT-29, and MDA-MB-231. Cells are treated with varying concentrations of the compound for 48-72 hours. Cell viability and proliferation are measured using standard assays. Neurogenic effects are assessed by evaluating neuronal differentiation markers. Akt signaling pathway activity is measured by Western blotting for phosphorylated Akt and downstream targets such as GSK-3β and mTOR. |
| Animal Protocol |
Animal/Disease Models: balb/c (Bagg ALBino) mouse: (nu/nu , female, 3-4 weeks old, 20-25 g) with 786-O and KHOS xenograft[1]
Doses: 12.5, 25, 50 mg/kg Route of Administration: Oral; one time/day for 22 days Experimental Results: demonstrated dose-dependent tumor growth inhibition. Animal/Disease Models: SD rats (male, 8 weeks old, 250-300 g)[1] Doses: 15 mg/kg (pharmacokinetic/PK Analysis) Route of Administration: Oral Experimental Results: Had a T1/2 of 8.68 hrs (hours), a Cmax of 171.17 ng/mL and an AUC of 2820.64 ng/mL·h. In vivo studies for Hu7691 free base are conducted in mouse tumor models. The compound is administered orally at doses determined by pharmacokinetic studies. Efficacy is assessed by measuring tumor growth inhibition. Cutaneous toxicity is evaluated by assessing skin reactions. Pharmacodynamic markers such as Akt phosphorylation and downstream signaling are evaluated in tumor tissues. However, specific published in vivo protocols are not detailed in the available literature. |
| ADME/Pharmacokinetics |
Hu7691 free base is orally active with favorable pharmacokinetic properties. It has a molecular weight of 414.42 g/mol. As a small molecule Akt inhibitor, it is expected to have good oral bioavailability. Storage conditions: powder at -20°C for 3 years or 4°C for 2 years; in solvent at -80°C for 6 months or -20°C for 1 month. Detailed PK parameters such as half-life and bioavailability are not extensively reported in the available literature.
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| Toxicity/Toxicokinetics |
Toxicity data for Hu7691 free base shows that it enables decrease of cutaneous toxicity in mice. This suggests a favorable safety profile compared to other Akt inhibitors. As with all research compounds, Hu7691 free base is intended for research use only and not for human therapeutic applications. Standard in vitro cytotoxicity assays and comprehensive toxicology studies would be required for clinical development.
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| References | |
| Additional Infomation |
Hu7691 free base is an orally active, potent, and selective Akt inhibitor with IC50s of 4.0 nM, 97.5 nM, and 28 nM for Akt1, Akt2, and Akt3, respectively. It has anti-proliferative and neurogenic effects on neuroblastoma cell lines. It inhibits the growth of 18 human tumor cell lines and inhibits tumor growth in mice. Hu7691 free base has a molecular weight of 414.42 g/mol and is a valuable tool for studying Akt signaling and developing cancer therapies.
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| Molecular Formula |
C22H21F3N4O
|
|---|---|
| Molecular Weight |
414.423555135727
|
| Exact Mass |
414.166
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| CAS # |
2241232-43-7
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| Related CAS # |
Hu7691;2360523-76-6
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| PubChem CID |
135274950
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
3
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
6
|
| Rotatable Bond Count |
4
|
| Heavy Atom Count |
30
|
| Complexity |
597
|
| Defined Atom Stereocenter Count |
2
|
| SMILES |
CN1C(=CC=N1)C2=CC(=C(C=C2)C(=O)N[C@@H]3CNCC[C@H]3C4=CC(=C(C=C4)F)F)F
|
| InChi Key |
PALTUSLCLFDFQQ-MGPUTAFESA-N
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| InChi Code |
InChI=1S/C22H21F3N4O/c1-29-21(7-9-27-29)14-2-4-16(18(24)11-14)22(30)28-20-12-26-8-6-15(20)13-3-5-17(23)19(25)10-13/h2-5,7,9-11,15,20,26H,6,8,12H2,1H3,(H,28,30)/t15-,20+/m0/s1
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| Chemical Name |
N-[(3S,4S)-4-(3,4-difluorophenyl)piperidin-3-yl]-2-fluoro-4-(2-methylpyrazol-3-yl)benzamide
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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) |
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
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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 | 2.4130 mL | 12.0651 mL | 24.1301 mL | |
| 5 mM | 0.4826 mL | 2.4130 mL | 4.8260 mL | |
| 10 mM | 0.2413 mL | 1.2065 mL | 2.4130 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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