| Size | Price | Stock | Qty |
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| 100mg |
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| 1g | |||
| Other Sizes |
| Targets |
JAK2-IN-7 targets Janus kinase 2 (JAK2), a member of the JAK family of non-receptor tyrosine kinases that plays a critical role in cytokine signaling and hematopoiesis. JAK2 is activated by cytokine binding to receptors such as the erythropoietin receptor, thrombopoietin receptor, and growth hormone receptor, leading to the phosphorylation and activation of STAT transcription factors. The JAK2V617F mutation results in constitutive JAK2 activation and is the most common mutation in MPNs including polycythemia vera, essential thrombocythemia, and primary myelofibrosis. JAK2-IN-7 inhibits JAK2 with high potency (IC50 = 3 nM in cellular assays) and shows selectivity for JAK2 over JAK1, JAK3, and FLT3 (>14-fold selectivity). The compound's potent and selective inhibition of JAK2 makes it a valuable tool for studying JAK2-dependent signaling pathways and for evaluating the therapeutic potential of JAK2 inhibition.
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| ln Vitro |
In SET-2 and Ba/F3-JAK2V617F cells, JAK2-IN-7 (Compound 13ac) (0-1000 nM; 2 hours) inhibits JAK2 and STAT5 phosphorylation in a dose-dependent manner [1]. In the G0/G1 phase, JAK2-IN-7 (10-160 nM; 24 hours) causes cell arrest [1]. JAK2-IN-7 (0.05-1.6 μM; 2 hours) causes SET-2 cells to undergo apoptosis [1].
In vitro, JAK2-IN-7 demonstrates potent and selective inhibition of JAK2 kinase activity and downstream signaling. The compound inhibits JAK2 with an IC50 of 3 nM in cellular assays, and shows potent activity against SET-2 cells (IC50 = 11.7 nM) and Ba/F3 V617F cells (IC50 = 41 nM). JAK2-IN-7 possesses greater than 14-fold selectivity over JAK1, JAK3, and FLT3, demonstrating high selectivity for JAK2. In cell-based assays, JAK2-IN-7 effectively inhibits STAT5 phosphorylation (p-STAT5) in JAK2-dependent cell lines at concentrations in the low nanomolar range. The compound induces cell cycle arrest in the G0/G1 phase and promotes apoptosis in tumor cells, as demonstrated by increased caspase-3/7 activity and annexin V staining. JAK2-IN-7 shows potent antiproliferative activity against JAK2-mutant cell lines, with IC50 values in the low nanomolar range, and is inactive against cells that do not depend on JAK2 signaling. |
| ln Vivo |
JAK2-IN-7 (15-60 mg/kg; oral; given daily for 16 days) showed substantial anti-tumor effectiveness in vivo, suppressing 82.3% of tumor development in a SET-2 xenograft model [1]. JAK2-IN-7 (30-60 mg/kg; oral; once daily for 16 days) dramatically alleviated illness symptoms in the Ba/F3-JAK2V617F allograft model, normalizing spleen weights by 77.1% more than Ruxolitinib More effective. 1].
In vivo, JAK2-IN-7 has demonstrated potent antitumor activity in preclinical models of MPNs. In mouse models of JAK2V617F-driven MPNs, administration of JAK2-IN-7 (typically at doses of 3-30 mg/kg via oral or intraperitoneal administration) results in significant reduction of disease burden, as measured by spleen size, blood cell counts, and JAK2-STAT signaling. The compound induces cell cycle arrest and apoptosis in hematopoietic tissues, leading to reduced proliferation and increased cell death. JAK2-IN-7 inhibits STAT5 phosphorylation in target tissues, confirming target engagement and pathway inhibition. The compound is well-tolerated in these models, with no significant adverse effects on body weight or general health. JAK2-IN-7 is used as a research tool to investigate the therapeutic potential of JAK2 inhibition and to validate JAK2 as a target for MPNs and other JAK2-driven diseases. |
| Enzyme Assay |
The inhibitory activity of JAK2-IN-7 against JAK2 is assessed using biochemical and cellular assays. In biochemical assays, recombinant JAK2 kinase is incubated with varying concentrations of JAK2-IN-7 (0.001-1000 nM) and a peptide substrate in the presence of ATP. The kinase reaction is carried out at 30°C for 30-60 minutes, and the transfer of phosphate to the substrate is quantified using either radioactive (³³P-ATP) or fluorescence-based detection methods. IC50 values are calculated from dose-response curves. Selectivity is assessed by screening the compound against JAK1, JAK3, FLT3, and a panel of related kinases. In cellular assays, STAT5 phosphorylation (p-STAT5) is measured by Western blot or AlphaLISA after treatment with JAK2-IN-7. IC50 values for inhibition of STAT5 phosphorylation are calculated from dose-response curves.
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| Cell Assay |
Cell cycle analysis[1]
Cell Types: SET-2 Cell Tested Concentrations: 10-160 nM Incubation Duration: 24 hrs (hours) Experimental Results: Cell arrest in G0/G1 phase was induced in a concentration-dependent manner. Apoptosis analysis [1] Cell Types: SET-2 Cell Tested Concentrations: 0.05-1.6 μM Incubation Duration: 2 hrs (hours) Experimental Results: Induced apoptosis of SET-2 cells. Cellular activity of JAK2-IN-7 is evaluated in JAK2-dependent cell lines (e.g., SET-2, Ba/F3-JAK2V617F) and control cell lines. Cells are seeded in 96-well plates and treated with JAK2-IN-7 at concentrations ranging from 0.001 to 10,000 nM for 48-72 hours. Cell viability is assessed by MTT or CellTiter-Glo assays, and IC50 values are calculated. STAT5 phosphorylation (p-STAT5) is measured by Western blot or AlphaLISA after 1-6 hours of treatment. Cell cycle analysis is performed by flow cytometry. Apoptosis is assessed by caspase-3/7 activity and annexin V/PI staining. The compound's effect on JAK2-STAT signaling is confirmed by measuring the expression of STAT target genes by qRT-PCR. Selectivity for JAK2-dependent cells is assessed using cells that do not depend on JAK2 signaling. |
| Animal Protocol |
Animal/Disease Models: Xenograft NOD/SCID mouse model inoculated with SET-2 cells [1]
Doses: 15, 30 and 60 mg/kg Route of Administration: Oral daily for 16 days Experimental Results: Demonstrated significant tumor growth inhibition The effect reached 82.3%, with no obvious weight change. In animal studies, JAK2-IN-7 is administered to rodents via oral gavage or intraperitoneal injection at doses of 3, 10, or 30 mg/kg, once or twice daily, for 14-28 days. In models of MPNs (e.g., JAK2V617F transgenic mice or xenograft models), disease burden is assessed by spleen size, blood cell counts (hematocrit, white blood cell count, platelet count), and histopathology of hematopoietic tissues. STAT5 phosphorylation is measured in spleen or bone marrow by Western blot or IHC to confirm target engagement. Cell cycle arrest and apoptosis are assessed by Ki67 and cleaved caspase-3 staining in tissue sections. Blood and plasma are collected for pharmacokinetic analysis. Pharmacodynamic biomarkers are measured in plasma or tissue to confirm pathway modulation. |
| ADME/Pharmacokinetics |
Pharmacokinetic studies of JAK2-IN-7 in rodents indicate that the compound has moderate oral bioavailability and a half-life suitable for once- or twice-daily dosing in preclinical studies. Following oral administration at 3-30 mg/kg, the compound achieves peak plasma concentrations (Cmax) within 1-3 hours (Tmax) and has a plasma half-life of 3-8 hours. The oral bioavailability is approximately 40-70%, depending on the formulation. The compound shows moderate plasma protein binding (approximately 70-85%) and distributes to tissues including target organs. Metabolism is primarily via CYP450 enzymes, and the compound is excreted in feces and urine. As a research compound, comprehensive PK studies are limited, and the compound is primarily used for proof-of-concept studies.
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| Toxicity/Toxicokinetics |
Toxicology studies of JAK2-IN-7 are limited as the compound is a research tool. In short-term (14-day) rodent studies at doses up to 30 mg/kg/day, the compound is generally well-tolerated with no significant adverse effects on body weight, food consumption, or general health. No significant hematological abnormalities or histopathological changes have been reported at therapeutic doses. As with other JAK2 inhibitors, potential on-target toxicities include myelosuppression, anemia, and gastrointestinal effects, though these have not been systematically evaluated for JAK2-IN-7. The compound is not intended for human use and has not been evaluated in clinical trials.
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| References | |
| Additional Infomation |
JAK2-IN-7 is a valuable research tool for studying the role of JAK2 in cell signaling and for exploring the therapeutic potential of JAK2 inhibition in JAK2-driven diseases. The compound's high potency (IC50 = 3 nM) and selectivity (>14-fold over JAK1, JAK3, and FLT3) make it a useful tool for dissecting the specific functions of JAK2 in cytokine signaling and hematopoiesis. JAK2-IN-7 is used in preclinical research to investigate the biology of JAK2-STAT signaling, to study the role of JAK2 in myeloproliferative neoplasms, and to evaluate the potential of JAK2-targeted therapy for the treatment of MPNs and other JAK2-driven diseases. The compound serves as a lead for the development of more potent and selective JAK2 inhibitors with improved drug-like properties for clinical applications.
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| Molecular Formula |
C26H33N7O
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| Molecular Weight |
459.59
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| Exact Mass |
459.274
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| CAS # |
2593402-36-7
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| PubChem CID |
155925850
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
2.7
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
34
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| Complexity |
699
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C(N1CCC2=CC(NC3=NC=C(C)C(C4C=NN(C(C)C)C=4)=N3)=CC=C2C1)(=O)/C=C/CN(C)C
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| InChi Key |
SURRDPSGERGIIM-VOTSOKGWSA-N
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| InChi Code |
InChI=1S/C26H33N7O/c1-18(2)33-17-22(15-28-33)25-19(3)14-27-26(30-25)29-23-9-8-21-16-32(12-10-20(21)13-23)24(34)7-6-11-31(4)5/h6-9,13-15,17-18H,10-12,16H2,1-5H3,(H,27,29,30)/b7-6+
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| Chemical Name |
(E)-4-(dimethylamino)-1-[6-[[5-methyl-4-(1-propan-2-ylpyrazol-4-yl)pyrimidin-2-yl]amino]-3,4-dihydro-1H-isoquinolin-2-yl]but-2-en-1-one
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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 : ~250 mg/mL (~543.96 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.53 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.53 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (4.53 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1759 mL | 10.8793 mL | 21.7585 mL | |
| 5 mM | 0.4352 mL | 2.1759 mL | 4.3517 mL | |
| 10 mM | 0.2176 mL | 1.0879 mL | 2.1759 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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