Physicochemical Properties
| Molecular Formula | C22H25FN8O |
| Molecular Weight | 436.485306501389 |
| Exact Mass | 436.213 |
| CAS # | 2764609-97-2 |
| PubChem CID | 163212188 |
| Appearance | Gray to dark gray solid powder |
| LogP | 3.1 |
| Hydrogen Bond Donor Count | 4 |
| Hydrogen Bond Acceptor Count | 9 |
| Rotatable Bond Count | 6 |
| Heavy Atom Count | 32 |
| Complexity | 597 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | C(NN)(=O)C1=CC=CC=C1NC1C(F)=CN=C(NC2=CC=C(N3CCN(C)CC3)C=C2)N=1 |
| InChi Key | MGPNQCUHKOUGKG-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C22H25FN8O/c1-30-10-12-31(13-11-30)16-8-6-15(7-9-16)26-22-25-14-18(23)20(28-22)27-19-5-3-2-4-17(19)21(32)29-24/h2-9,14H,10-13,24H2,1H3,(H,29,32)(H2,25,26,27,28) |
| Chemical Name | 2-[[5-fluoro-2-[4-(4-methylpiperazin-1-yl)anilino]pyrimidin-4-yl]amino]benzohydrazide |
| 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 | IC50: 47 nM (BTK); 12 nM (FLT3)[1] |
| ln Vitro | For Jeko-1, MV-4-11, Molt4, and K562 cells, RSH-7 (1-1000 nM; 72 h) exhibits antiproliferative activities with IC50s of 17, 3, 11, and 930 nM, respectively[1]. The expression of p-BTK (TYR223), p-PLCγ (Tyr1217), p-FLT3 (Tyr589), and p-STAT5 (TYR694) is reduced in a dose-dependent manner by RSH-7 (30, 150, 750 nM; 72 h)[1]. In Jeko-1 cells, RSH-7 (30, 150, 750 nM; 72 h) dose-dependently induces apoptosis and upregulates the expression of BAX, p53, and cleaved caspase 3[1]. |
| ln Vivo | RSH-7 (25, 50 mg/kg; ip; daily for 16 days) shows anti-tumor activity with significantly and dose-dependently suppresses the tumor growth in mouse[1]. |
| Cell Assay |
Cell Viability Assay[1] Cell Types: Jeko-1, MV-4-11, Molt4, K562 cells Tested Concentrations: 1-1000 nM Incubation Duration: 72 h Experimental Results: demonstrated antiproliferative activities with IC50s of 17, 3, 11, 930 nM for Jeko-1, MV -4-11, Molt4, K562 cells, respectively. Western Blot Analysis[1] Cell Types: jeko-1 cells Tested Concentrations: 30, 150, 750 nM Incubation Duration: 72 h Experimental Results: diminished both BTK, PLCγ2, FLT3 and STAT5 phosphorylation in a dose-dependent manner. Apoptosis Analysis[1] Cell Types: jeko-1 cells Tested Concentrations: 30, 150, 750 nM Incubation Duration: 72 h Experimental Results: Dose-dependently induced cell apoptosis and upregulated the expression of pro-apoptotic protein BAX , p53, cleaved caspase 3. |
| Animal Protocol |
Animal/Disease Models: Female NOD/SCID (severe combined immunodeficient) mouse (jeko- 1 cell-inoculated xenograft NOD/SCID (severe combined immunodeficient) mouse models)[1] Doses: 25, 50 mg/kg Route of Administration: Ip; daily for 16 days Experimental Results: Suppressed tumor growth in a dose-dependent manner, with tumor growth inhibition (TGI) values of 66.95% and 79.78% at doses of 25 and 50 mg/kg. Animal/Disease Models: Female NOD/SCID (severe combined immunodeficient) mouse (MV4-11 cell-inoculated xenograft NOD/SCID mice)[1] Doses: 10, 20 mg/kg Route of Administration: Ip; daily for 21 days Experimental Results: Dramatically and dose-dependently suppressed the tumor growth with the TGI rates of 74.23% and 94.84% at the dosage of 10 and 20 mg/kg, respectively. |
| References |
[1]. Development of novel hydrazidoarylaminopyrimidine-based BTK/FLT3 dual inhibitors with potent in vivo anti-hematological malignancies effects. Eur J Med Chem. 2023 Jan 5;245(Pt 1):114913. |
Solubility Data
| Solubility (In Vitro) | DMSO: 83.33 mg/mL (190.91 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 | 2.2910 mL | 11.4550 mL | 22.9100 mL | |
| 5 mM | 0.4582 mL | 2.2910 mL | 4.5820 mL | |
| 10 mM | 0.2291 mL | 1.1455 mL | 2.2910 mL |