Physicochemical Properties
| Molecular Formula | C14H9CLF3NO3 |
| Molecular Weight | 331.67 |
| Exact Mass | 331.022 |
| Elemental Analysis | C, 50.70; H, 2.74; Cl, 10.69; F, 17.18; N, 4.22; O, 14.47 |
| CAS # | 205754-33-2 |
| Related CAS # | 205754-33-2 |
| PubChem CID | 487643 |
| Appearance | White to off-white solid powder |
| Density | 1.6±0.1 g/cm3 |
| Boiling Point | 373.6±42.0 °C at 760 mmHg |
| Melting Point | 144-154ºC |
| Flash Point | 179.7±27.9 °C |
| Vapour Pressure | 0.0±0.9 mmHg at 25°C |
| Index of Refraction | 1.608 |
| LogP | 4.8 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 6 |
| Rotatable Bond Count | 1 |
| Heavy Atom Count | 22 |
| Complexity | 551 |
| Defined Atom Stereocenter Count | 1 |
| SMILES | ClC1=CC(O)=C2C([C@](C(F)(F)F)(C#CC3CC3)OC(N2)=O)=C1 |
| InChi Key | OOVOMPCQLMFEDT-ZDUSSCGKSA-N |
| InChi Code | InChI=1S/C14H9ClF3NO3/c15-8-5-9-11(10(20)6-8)19-12(21)22-13(9,14(16,17)18)4-3-7-1-2-7/h5-7,20H,1-2H2,(H,19,21)/t13-/m0/s1 |
| Chemical Name | (4S)-6-chloro-4-(2-cyclopropylethynyl)-8-hydroxy-4-(trifluoromethyl)-1H-3,1-benzoxazin-2-one |
| Synonyms | 8-hydroxy Efavirenz |
| 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 | 8-Hydroxyefavirenz (8-OH-EFV; 1–10 μM; 3–24 h; primary human hepatocytes) stimulates the production of ROS in the mitochondria of primary human hepatocytes and increases cell death in a manner that is dependent on time and concentration [1]. It also initiates caspase-3 activity at 6 hours. JNK is activated by 8-hydroxyefavirenz (10 μM; 3–24 h), which also causes a 4.2-fold increase in the ratio of pure phosphorylated JNK to total JNK. BimEL mRNA and protein expression are upregulated by 8-hydroxyefavirenz [1]. |
| Cell Assay |
Cell viability assay [1] Cell Types: primary human hepatocytes Tested Concentrations: 1 and 10 μM Incubation Duration: 3, 6, 12 and 24 Experimental Results: Increased cell death in a time- and concentration-dependent manner, with an increase of 3.4 at 6 hrs (hours) times. Western Blot Analysis[1] Cell Types: Primary human hepatocytes Tested Concentrations: 1 and 10 μM Incubation Duration: 3, 6, 12 and 24 hrs (hours) Experimental Results: Increased expression of cleaved caspase-3 in a time- and concentration-dependent manner. Western Blot Analysis[1] Cell Types: Primary Human Hepatocytes Tested Concentrations: 1 and 10 μM Incubation Duration: 3, 6, 12 and 24 hrs (hours) Experimental Results: Increased JNK phosphorylation, increased BimEL mRNA and protein expression. |
| ADME/Pharmacokinetics |
Metabolism / Metabolites 8-hydroxyefavirenz has known human metabolites that include 8,14-dihydroxy-efavirenz and (2S,3S,4S,5R)-6-[[(4S)-6-chloro-4-(2-cyclopropylethynyl)-2-oxo-4-(trifluoromethyl)-1H-3,1-benzoxazin-8-yl]oxy]-3,4,5-trihydroxyoxane-2-carboxylic acid. 8-hydroxyefavirenz is a known human metabolite of efavirenz. |
| References |
[1]. Bumpus NN. Efavirenz and 8-hydroxyefavirenz induce cell death via a JNK- and BimEL-dependent mechanism in primary human hepatocytes. Toxicol Appl Pharmacol. 2011 Dec 1;257(2):227-34. |
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 | 3.0150 mL | 15.0752 mL | 30.1505 mL | |
| 5 mM | 0.6030 mL | 3.0150 mL | 6.0301 mL | |
| 10 mM | 0.3015 mL | 1.5075 mL | 3.0150 mL |