JE-2147(AG1776), a hybrid peptide compound, is a novel and potent dipeptide protease inhibitor with antiviral effects. It inhibits HIV-1 protease with a Ki of 0.33 nM.
Physicochemical Properties
| Molecular Formula | C32H37N3O5S |
| Molecular Weight | 575.72 |
| Exact Mass | 575.245 |
| CAS # | 186538-00-1 |
| PubChem CID | 446837 |
| Appearance | Typically exists as solid at room temperature |
| Density | 1.258g/cm3 |
| Boiling Point | 861.5ºC at 760mmHg |
| Flash Point | 474.8ºC |
| Vapour Pressure | 1.2E-31mmHg at 25°C |
| Index of Refraction | 1.623 |
| LogP | 5.06 |
| Hydrogen Bond Donor Count | 4 |
| Hydrogen Bond Acceptor Count | 6 |
| Rotatable Bond Count | 9 |
| Heavy Atom Count | 41 |
| Complexity | 910 |
| Defined Atom Stereocenter Count | 3 |
| SMILES | O=C([C@H]1N(C([C@@H](O)[C@@H](NC(C2=CC=CC(O)=C2C)=O)CC3=CC=CC=C3)=O)CSC1(C)C)NCC4=CC=CC=C4C |
| InChi Key | CUFQBQOBLVLKRF-RZDMPUFOSA-N |
| InChi Code | InChI=1S/C32H37N3O5S/c1-20-11-8-9-14-23(20)18-33-30(39)28-32(3,4)41-19-35(28)31(40)27(37)25(17-22-12-6-5-7-13-22)34-29(38)24-15-10-16-26(36)21(24)2/h5-16,25,27-28,36-37H,17-19H2,1-4H3,(H,33,39)(H,34,38)/t25-,27-,28+/m0/s1 |
| Chemical Name | (4R)-3-[(2S,3S)-2-hydroxy-3-[(3-hydroxy-2-methylbenzoyl)amino]-4-phenylbutanoyl]-5,5-dimethyl-N-[(2-methylphenyl)methyl]-1,3-thiazolidine-4-carboxamide |
| Synonyms | AG 1776 AG1776 JE-2147 |
| 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
| ln Vitro | JE-2147 (0.01-0.05 μM; 7 days; PBMC and MT-2 cells) demonstrates exceptionally strong antiviral activity against HIV-1, with IC50s against HIV-1 LAI (SI) of 44 nM, 24 nM, and 35 nM, in that order. HIV-1Ba-L (SI), HIV-1LAI (NSI), HIV-2EHO (SI), and 47 nM, in that order [1]. With IC50 values ranging from 31 to 160 nM, JE-2147 is highly effective against HIV-1 IIIB replication in a range of cells, including T cells, B cells, macrophages, and PBMCs. It also exhibits antiviral efficacy against HIV-2 and the simian immunodeficiency virus[2]. |
| ln Vivo | JE-2147 demonstrates good oral bioavailability and plasma pharmacokinetic characteristics in dogs and rats [2]. Pharmacokinetic characteristics of JE-2147 in beagle dogs and male Sprague-Dawley rats [2]. Sprague-Dawley Rat Beagle Dog iv, 10 mg/kg id, 10 mg/kg iv, 25 mg/kg po (fed), 25 mg/kg po (fasted), 25 mg/kg t1/2β (min) 93 / 94 / / Cmax (μM) / 0.70 ± 0.20 / 4.02 ± 0.72 5.30 ± 1.13 Tmax (min) / 60 / 90 60 F (%) / 41.6 ± 10.7 / 32.6 ± 0.06 37.1 ± 0.08 CL (L/h/kg ) // 0.88 ± 0.09 // Vd, ss (L/kg) // 1.58 // AUC0-24 (μM·min) // / 1009 1149 |
| Animal Protocol |
Animal/Disease Models: Beagle dog and male SD (SD (Sprague-Dawley)) rat[2] Doses: 25 mg/kg for dogs; 10 mg/kg for rats. Route of Administration: rats iv and id; intravenously (iv) (iv)(iv) and orally for dogs. Experimental Results: demonstrated good pharmacokinetic/PK/PK properties. |
| References |
[1]. JE-2147: a dipeptide protease inhibitor (PI) that potently inhibits multi-PI-resistant HIV-1. Proc Natl Acad Sci U S A. 1999 Jul 20;96(15):8675-80. [2]. Structure-activity relationship of small-sized HIV protease inhibitors containing allophenylnorstatine. J Med Chem. 1999 May 20;42(10):1789-802. |
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 | 1.7370 mL | 8.6848 mL | 17.3696 mL | |
| 5 mM | 0.3474 mL | 1.7370 mL | 3.4739 mL | |
| 10 mM | 0.1737 mL | 0.8685 mL | 1.7370 mL |