Physicochemical Properties
| Molecular Formula | C31H29CLN8O5 |
| Molecular Weight | 629.065564870834 |
| CAS # | 2744293-04-5 |
| Appearance | Typically exists as solid at room temperature |
| 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 | FXIa-IN-8 (compound 35) has considerable anticoagulant effect on the intrinsic pathway (0-250 µg/mL) but not on the extrinsic pathway [1]. |
| ln Vivo | Selectivity for FXIa and PKal is demonstrated by FXIa-IN-8, whose IC50 values are 14.2 and 27900 nM, respectively[1]. FXIa-IN-8 exhibits antithrombotic activity in vivo at doses of 6.5 and 19.5 mg/kg (iv) [1]. FXIa-IN-8 did not exhibit any acute toxicity at 50 or 100 mg/kg (iv) [1]. The PK features of FXIa-IN-8 (10 mg/kg; iv) are moderate [1]. Compared to 300 IU/kg heparin sodium, FXIa-IN-8 (19.5, 39 mg/kg) has a significantly lower bleeding risk [1]. FXIa-IN-8 pharmacokinetic parameters in male SD rats [1]. Compound 35 T1/2 (h) Cmax (μg/mL) AUC0-t (h·μg/mL) AUC0-∞ (h·μg/mL) Vz (mL/kg) Cl (mL/h/kg) MRT0- t (h) iv (10 mg/kg) 1.26 57 18.3 18.4 969 553 0.32 Male SD rats; intravenous injection of 10 mg/kg [1]. |
| Animal Protocol |
Animal/Disease Models: Male SD rat [1] Doses: 10 mg/kg (300 IU/kg (2.7 mg/kg) heparin sodium is injected into the tail vein 10 minutes before surgery) Route of Administration: intravenous (iv) (iv)injection Experimental Results:shows a moderate PK curve, The half-life (T1/2) is 1.26 hrs (hrs (hours)) and the clearance (Cl) value is 553 mL/h/kg. Animal/Disease Models: C57BL/6J mice (FeCl3-induced carotid artery thrombosis model) [1] Doses: 6.5, 19.5 mg/kg Route of Administration: intravenous (iv) (iv)injection Experimental Results: The occlusion time was slightly prolonged at the 6.5 mg/kg dose, and at 6.5 Exhibits excellent antithrombotic activity at a mg/kg dose of 35 mg/kg. Animal/Disease Models: ICR mice [1] Doses: 50, 100 mg/kg Route of Administration: intravenous (iv) (iv)injection Experimental Results: No obvious toxic reactions were found in different tissues of mice. Animal/Disease Models: C57BL/6J mice [1] Doses: 19.5, 39, 20, 60, 100 mg/kg Route of Administration: intravenous (iv) (iv)injection Experimental Results: The risk of bleeding was low at doses of 60 and 100 mg/kg. |
| References |
[1]. Targeting the S2 Subsite Enables the Structure-Based Discovery of Novel Highly Selective Factor XIa Inhibitors. J Med Chem. 2022; 65(5):4318-4334. |
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 | 1.5896 mL | 7.9482 mL | 15.8965 mL | |
| 5 mM | 0.3179 mL | 1.5896 mL | 3.1793 mL | |
| 10 mM | 0.1590 mL | 0.7948 mL | 1.5896 mL |