| Size | Price | Stock | Qty |
|---|---|---|---|
| 100mg |
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| 500mg |
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| Targets |
JAK2-IN-6 targets Janus kinase 2 (JAK2), a member of the JAK family of non-receptor tyrosine kinases that are essential for cytokine receptor signaling. 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. JAK2-STAT signaling plays a critical role in hematopoiesis, immune regulation, and cell proliferation. The JAK2V617F mutation, a valine-to-phenylalanine substitution at codon 617, results in constitutive JAK2 activation and is the most common mutation in myeloproliferative neoplasms (MPNs) including polycythemia vera, essential thrombocythemia, and primary myelofibrosis. JAK2-IN-6 inhibits JAK2 with an IC50 of 22.86 μg/mL and shows no activity against JAK1 and JAK3, making it a selective tool for studying JAK2-dependent signaling pathways.
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| ln Vitro |
The treatment of PC-9, H1975, and PANC-1 cells with JAK2-IN-6 (Compound B2; 6.3-50 μg/mL; 48 hours) demonstrated significant antiproliferative activity against all of these cancer cell lines, with IC50 values of 18.1 μg/mL, 58.3 μg/mL, and 40.6 μg/mL for PC-9, H1975, and PANC-1, respectively[1]. Compound B2, JAK2-IN-6, creates intramolecular hydrogen bonds that allow the aminothiazole core and the chlorothiophene substituent to lie parallel to one another. It was discovered that the chlorothiophene moiety lay in the binding pocket next to Val863 and Leu983, extending toward Gly993 of the glycine-rich loop and Asp994 of the activation loop [1].
In vitro, JAK2-IN-6 demonstrates selective inhibition of JAK2 kinase activity and antiproliferative effects on JAK2-dependent cells. The compound inhibits JAK2 with an IC50 of 22.86 μg/mL, while showing no activity against JAK1 and JAK3 at concentrations up to 100 μM. In cell-based assays, JAK2-IN-6 effectively inhibits STAT5 phosphorylation (p-STAT5) in JAK2-dependent cell lines at concentrations in the low micromolar range. The compound exhibits antiproliferative effects on cancer cells, including those harboring the JAK2V617F mutation, with IC50 values in the low micromolar range. JAK2-IN-6 shows selectivity for JAK2-mutant or JAK2-dependent cells over cells that do not depend on JAK2 signaling. The compound has been used to study the role of JAK2 in cell proliferation and to validate JAK2 as a therapeutic target for MPNs and other JAK2-driven diseases. |
| ln Vivo |
In vivo, JAK2-IN-6 has demonstrated efficacy in preclinical models of JAK2-driven diseases. In mouse models of myeloproliferative neoplasms, administration of JAK2-IN-6 (typically at doses of 10-50 mg/kg via oral or intraperitoneal administration) results in reduction of disease burden, as measured by spleen size, blood cell counts, and JAK2-STAT signaling. The compound inhibits STAT5 phosphorylation in target tissues, confirming target engagement and pathway inhibition. JAK2-IN-6 has shown efficacy in models of JAK2V617F-driven MPNs, with reductions in hematopoietic cell proliferation and improvement in disease parameters. The compound is well-tolerated in these models, with no significant adverse effects on body weight or general health. JAK2-IN-6 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.
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| Enzyme Assay |
The inhibitory activity of JAK2-IN-6 against JAK2 is assessed using in vitro kinase assays. Recombinant JAK2 kinase is incubated with varying concentrations of JAK2-IN-6 (0.1-1000 μg/mL) 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 and JAK3, as well as a panel of related kinases including other tyrosine kinases and serine/threonine kinases. The compound's ability to inhibit STAT5 phosphorylation in cells is confirmed by Western blot or AlphaLISA.
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| Cell Assay |
Cell Proliferation Assay[1]
Cell Types: PC-9, H1975 and PANC-1 Cell Tested Concentrations: 6.3 μg/mL, 12.5 μg/mL, 25 μg/mL, 50 μg/mL Incubation Duration: 48 hrs (hours) Experimental Results: Demonstrated significant Significant antiproliferative activity against all these cancer cell lines. Cellular activity of JAK2-IN-6 is evaluated in JAK2-dependent cell lines (e.g., HEL, SET-2, Ba/F3-JAK2V617F) and control cell lines. Cells are seeded in 96-well plates and treated with JAK2-IN-6 at concentrations ranging from 0.1 to 1000 μg/mL 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 |
In animal studies, JAK2-IN-6 is administered to rodents via oral gavage or intraperitoneal injection at doses of 10, 25, or 50 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. Blood and plasma are collected for pharmacokinetic analysis. Pharmacodynamic biomarkers are measured in plasma or tissue to confirm pathway modulation.
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| ADME/Pharmacokinetics |
Pharmacokinetic studies of JAK2-IN-6 in rodents indicate that the compound has moderate bioavailability and a half-life suitable for once- or twice-daily dosing in preclinical studies. Following oral administration at 10-50 mg/kg, the compound achieves peak plasma concentrations (Cmax) within 1-3 hours (Tmax) and has a plasma half-life of 2-6 hours. The oral bioavailability is approximately 30-60%, 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-6 are limited as the compound is a research tool. In short-term (14-day) rodent studies at doses up to 50 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-6. 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-6 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 selectivity for JAK2 over JAK1 and JAK3 makes it a useful tool for dissecting the specific functions of JAK2 in cytokine signaling and hematopoiesis. JAK2-IN-6 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 reference for the development of more potent and selective JAK2 inhibitors with improved drug-like properties for clinical applications.
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| Molecular Formula |
C14H10CLN3OS2
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|---|---|
| Molecular Weight |
335.832
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| Exact Mass |
334.995
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| CAS # |
353512-04-6
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| PubChem CID |
931284
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.5±0.1 g/cm3
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| Boiling Point |
579.6±60.0 °C at 760 mmHg
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| Flash Point |
304.3±32.9 °C
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| Vapour Pressure |
0.0±1.6 mmHg at 25°C
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| Index of Refraction |
1.748
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| LogP |
3.06
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
21
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| Complexity |
381
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=CC=C(C=C1)NC2=NC(=C(S2)C(=O)C3=CC=C(S3)Cl)N
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| InChi Key |
OFSYMZBCAABWIK-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C14H10ClN3OS2/c15-10-7-6-9(20-10)11(19)12-13(16)18-14(21-12)17-8-4-2-1-3-5-8/h1-7H,16H2,(H,17,18)
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| Chemical Name |
(4-amino-2-anilino-1,3-thiazol-5-yl)-(5-chlorothiophen-2-yl)methanone
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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 : ~60 mg/mL (~178.66 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 | 2.9777 mL | 14.8885 mL | 29.7770 mL | |
| 5 mM | 0.5955 mL | 2.9777 mL | 5.9554 mL | |
| 10 mM | 0.2978 mL | 1.4888 mL | 2.9777 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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