Physicochemical Properties
| Molecular Formula | C22H21F3N4O |
| Molecular Weight | 414.423555135727 |
| Exact Mass | 414.166 |
| CAS # | 2241232-43-7 |
| Related CAS # | Hu7691;2360523-76-6 |
| PubChem CID | 135274950 |
| Appearance | Typically exists as solid at room temperature |
| 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 |
| 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 |
| Chemical Name | N-[(3S,4S)-4-(3,4-difluorophenyl)piperidin-3-yl]-2-fluoro-4-(2-methylpyrazol-3-yl)benzamide |
| 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) |
Biological Activity
| 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) |
| 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]. |
| 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]. |
| 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). |
| 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. |
| References |
[1]. Discovery of N-((3 S,4 S)-4-(3,4-Difluorophenyl)piperidin-3-yl)-2-fluoro-4-(1-methyl-1 H-pyrazol-5-yl)benzamide (Hu7691), a Potent and Selective Akt Inhibitor That Enables Decrease of Cutaneous Toxicity. J Med Chem. 2021 Aug 26;64(16):1. |
Solubility Data
| 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 (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *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). 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)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL 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). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (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 |