Physicochemical Properties
| Molecular Formula | C21H23CL3N4 |
| Molecular Weight | 437.79 |
| Exact Mass | 436.098 |
| CAS # | 1782228-59-4 |
| PubChem CID | 71433630 |
| Appearance | Typically exists as solid at room temperature |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 3 |
| Rotatable Bond Count | 4 |
| Heavy Atom Count | 28 |
| Complexity | 544 |
| Defined Atom Stereocenter Count | 1 |
| SMILES | CC[C@H]1CN2C3=C(N1CC4CC4)C=C(N=C3C(=N2)C5=C(C=C(C=C5)Cl)Cl)C.Cl |
| InChi Key | LNYUWBPFYXPUIO-RSAXXLAASA-N |
| InChi Code | InChI=1S/C21H22Cl2N4.ClH/c1-3-15-11-27-21-18(26(15)10-13-4-5-13)8-12(2)24-20(21)19(25-27)16-7-6-14(22)9-17(16)23;/h6-9,13,15H,3-5,10-11H2,1-2H3;1H/t15-;/m0./s1 |
| Chemical Name | (10S)-9-(cyclopropylmethyl)-3-(2,4-dichlorophenyl)-10-ethyl-6-methyl-1,2,5,9-tetrazatricyclo[6.3.1.04,12]dodeca-2,4,6,8(12)-tetraene;hydrochloride |
| 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 | CRFR1 4 nM (Ki) CRFR1 8.5 (pKi) |
| ln Vitro | NBI 35965 hydrochloride shows high affinity for CRF1 but no binding affinity for CRF2. In CRF1 transfected cells, NBI 35965 hydrochloride also inhibits sauvineine-induced cAMP stimulation [2]. |
| ln Vivo | NBI 35965 hydrochloride (20 mg/kg; oral gavage; once) reduces stress-induced ACTH production in mice[1]. In rats, NBI 35965 hydrochloride (compound 12a; 10 mg/kg) has a volume of distribution of 17.8 L/kg, a plasma clearance of 17 mL/min/kg, and a half-life of 12 hours. The estimated oral bioavailability is 34%, with a mean maximum plasma concentration of 560 ng/mL at 1 hour. NBI 35965 hydrochloride also crosses the blood-brain barrier, resulting in a mean maximum brain concentration of 700 ng/g[1]. |
| Animal Protocol |
Animal/Disease Models: Male CD-1 mice (24-26 g) bearing restraint stress[1] Doses: 20 mg/kg (10 mL/kg 5% mannitol-d (w/v) in water) Route of Administration: Oral gavage; 60 min prior to the initiation of the stressor Experimental Results: Reduced stress induced ACTH production in vivo. |
| References |
[1].Design and synthesis of tricyclic corticotropin-releasing factor-1 antagonists. J Med Chem. 2005 Sep 8;48(18):5780-93. [2].A novel water-soluble selective CRF1 receptor antagonist, NBI 35965, blunts stress-induced visceral hyperalgesia and colonic motor function in rats. Brain Res. 2003 Sep 19;985(1):32-42. |
Solubility Data
| Solubility (In Vitro) | Typically soluble in DMSO (e.g. 10 mM) |
| 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 | 2.2842 mL | 11.4210 mL | 22.8420 mL | |
| 5 mM | 0.4568 mL | 2.2842 mL | 4.5684 mL | |
| 10 mM | 0.2284 mL | 1.1421 mL | 2.2842 mL |