Physicochemical Properties
| Molecular Formula | C25H28N6O3S |
| Molecular Weight | 492.59 |
| CAS # | 3024090-08-9 |
| 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
| Targets | FGFR4WT 17.1 nM (IC50) FGFR3 29.6 nM (IC50) FGFR4V550L 30.7 nM (IC50) FGFR2 46.7 nM (IC50) FGFR1 64.3 nM (IC50) |
| ln Vitro | FGFR-IN-9(Compound 19)(0-2 mM; 72 h) suppresses the proliferation of Ba/F3 FGFR4WT and Ba/F3 FGFR4V550L cells with IC50s of 82.5 ± 19.2 nM and 82.5 nM, respectively, and inhibits HUH7 cells with an IC50 of 94.7±28.6 nM. 260.0 ± 50.2 nM was reported [1]. Inhibiting the FGFR signaling pathway, FGFR-IN-9 (0-400 nM; 4 h)[1]. |
| ln Vivo | Compound 19 (FGFR-IN-9) In the HUH7 xenograft mouse model, (30 and 45 mg/kg; ir; daily for 3 weeks) has anti-tumor efficacy [1]. FGFR-IN-9 (Compound 19) In Vivo Pharmacokinetic Profile Information [1] T1/2 (h) FGFR-IN-9 iv 1 mg/kg po 10 mg/kg 1.75 965 AUCINF (h·ng/mL) 177 1087 MRTinf (h) 1.3 2.37 Tmax (h) / 2 Cmax (ng /mL) / 202 AUCmax (h·ng/mL) and so on 3.87 F (%) / 61.5 VSS (L/kg) = 1.13 6.37 / CL (L/h / kg) 5.65 / |
| Cell Assay |
Western Blot Analysis[1] Cell Types: Ba/F3-TEL-FGFR4 cells Tested Concentrations: 0, 50, 100, 200 and 400 nM Incubation Duration: 4 h Experimental Results: demonstrated dose-dependent inhibition of the FGFR4 signal cassette, including the phosphorylation of FGFR4 and its downstream effectors FRS2 and PLCγ. |
| Animal Protocol |
Animal/Disease Models: Female BALB/c nude mice, HUH7 xenograft model[1] Doses: 30 and 45 mg/kg Route of Administration: intragastric (po) gavage; daily for 3 weeks Experimental Results: Resulted in significant tumor growth inhibition with a TGI value of 81% and an IR value of 63% at a dose of 45 mg/kg. No significant body weight loss (<5%) was observed. Animal/Disease Models: Male CD-1 mice[1] Doses: 1 mg/kg and 10 mg/kg Route of Administration: iv and po (pharmacokinetic/PK Analysis) Experimental Results: demonstrated good in vivo pharmacokinetic/PK profile. |
| References |
[1]. Discovery of 2-Amino-7-sulfonyl-7 H-pyrrolo [2, 3-d] pyrimidine Derivatives as Potent Reversible FGFR Inhibitors with Gatekeeper Mutation Tolerance: Design, Synthesis, and Biological Evaluation. Journal of Medicinal Chemistry, 2022. |
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 | 2.0301 mL | 10.1504 mL | 20.3009 mL | |
| 5 mM | 0.4060 mL | 2.0301 mL | 4.0602 mL | |
| 10 mM | 0.2030 mL | 1.0150 mL | 2.0301 mL |