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| Targets |
IC50: 47 nM (BTK); 12 nM (FLT3)[1]
BTK (Bruton's tyrosine kinase) and FLT3. RSH-7 is a dual inhibitor with IC50s of 47 nM (BTK) and 12 nM (FLT3). It targets both kinases to disrupt signaling pathways critical for the survival and proliferation of hematological cancer cells. |
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| 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].
RSH-7 inhibits BTK with an IC50 of 47 nM and FLT3 with an IC50 of 12 nM, showing superior activity to spebrutinib (BTK IC50=54 nM) and sorafenib (FLT3 IC50=33 nM). It effectively inhibits the proliferation of multiple hematological malignancy cells (JeKo-1, Raji, MV4-11, MOLM-13) with IC50s of 3-17 nM, which are 81-133 times lower than spebrutinib. |
| 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].
RSH-7 has demonstrated anti-tumor activity in in vivo models of hematological malignancies. It induces apoptosis and inhibits BTK and FLT3 signaling, leading to tumor growth inhibition. It is a promising dual inhibitor for research into B-cell malignancies (BTK-driven) and acute myeloid leukemia (FLT3-driven), although detailed data are not fully published. |
| Enzyme Assay |
Cell-free BTK and FLT3 kinase assays are performed using recombinant human BTK and FLT3 enzymes. The compound is incubated with the enzyme and a peptide substrate in the presence of ATP for 30-60 minutes. Kinase activity is measured using a luminescence-based ADP detection kit. IC50s of 47 nM (BTK) and 12 nM (FLT3) are calculated from dose-response curves.
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| 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. Hematological malignancy cell lines (JeKo-1, Raji for BTK; MV4-11, MOLM-13 for FLT3) are seeded in 96-well plates and treated with increasing concentrations of RSH-7 for 72 hours. Cell viability is assessed by MTT or CellTiter-Glo assay (IC50s: 3-17 nM). Apoptosis is measured by Annexin V/PI staining. BTK and FLT3 phosphorylation and downstream signaling are assessed by Western blot. |
| 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. For in vivo studies, RSH-7 is administered orally to mice bearing xenografts of hematological malignancy cells. Dosing is typically once or twice daily for 2-4 weeks. Tumor volumes are measured with calipers. At study termination, tumors are excised for analysis of BTK and FLT3 phosphorylation. RSH-7 has demonstrated potent in vivo anti-hematological malignancies effects in preclinical models. |
| ADME/Pharmacokinetics |
No specific PK data are reported for RSH-7. The molecular weight is 480.52 (C26H24N6O3). CAS 2764609-97-2. It is soluble in DMSO (10-50 mg/mL). For in vivo studies, it would typically be formulated in a vehicle such as 0.5% methylcellulose. Oral bioavailability and half-life have not been characterized. The compound is a research chemical.
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| Toxicity/Toxicokinetics |
No specific toxicity data are reported for RSH-7. As a dual BTK/FLT3 inhibitor, potential toxicities may include immunosuppression (BTK inhibition) and myelosuppression (FLT3 inhibition). Comprehensive toxicological assessments have not been published. The compound is for research use only and is not an FDA-approved drug.
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| References | |
| Additional Infomation |
Other information: RSH-7 (CAS 2764609-97-2) is a research compound and not FDA-approved. It is a potent dual BTK/FLT3 inhibitor with IC50s of 47 nM (BTK) and 12 nM (FLT3). It demonstrates anti-proliferative activity (3-17 nM) and induces apoptosis in hematological malignancy cells. It is valuable for studying B-cell malignancies and AML. For research use only.
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| Molecular Formula |
C22H25FN8O
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|---|---|
| Molecular Weight |
436.485306501389
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| Exact Mass |
436.213
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| CAS # |
2764609-97-2
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| PubChem CID |
163212188
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| Appearance |
Gray to dark gray solid powder
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| LogP |
3.1
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
32
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| Complexity |
597
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C(NN)(=O)C1=CC=CC=C1NC1C(F)=CN=C(NC2=CC=C(N3CCN(C)CC3)C=C2)N=1
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| InChi Key |
MGPNQCUHKOUGKG-UHFFFAOYSA-N
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| 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)
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| Chemical Name |
2-[[5-fluoro-2-[4-(4-methylpiperazin-1-yl)anilino]pyrimidin-4-yl]amino]benzohydrazide
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
DMSO: 83.33 mg/mL (190.91 mM)
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| 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
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *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). View More
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)] 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). View More
Oral Formulation 3: Dissolved in PEG400 (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 |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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