| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| Other Sizes |
| Targets |
JAK/HDAC-IN-1 primarily targets JAK2 and HDAC enzymes. It shows IC50s of 4 nM for JAK2 and 2 nM for HDAC. Additionally, it exhibits IC50 values of 4.8 nM for JAK1, 7.4 nM for JAK3, and 49 nM for TYK2, and 14 nM, 120 nM, and 2470 nM for HDAC2, HDAC6, and HDAC8, respectively. JAK2 is a non-receptor tyrosine kinase critical for cytokine signaling, while HDACs are enzymes that remove acetyl groups from histones, affecting gene expression. By simultaneously inhibiting both, the compound disrupts multiple oncogenic pathways.
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| ln Vitro |
JAK/HDAC-IN-1 (compound 8m) has IC50 values of 4.8, 7.4, and 49 nM against JAK1, JAK3, and TYK2, and 14, 120, and 2470 nM against HDAC2, HDAC6, and HDAC8, respectively [1].
In vitro, JAK/HDAC-IN-1 exhibits potent antiproliferative and proapoptotic effects in various hematological cancer cell lines. The dual inhibition of JAK2 and HDAC leads to cell cycle arrest and apoptosis. The compound's activity is characterized by its ability to inhibit both JAK2-mediated STAT signaling and HDAC-mediated epigenetic regulation, resulting in synergistic anticancer effects. Its selectivity profile against different JAK and HDAC isoforms allows for a nuanced modulation of these pathways, making it a powerful tool for dissecting their roles in cancer biology. |
| ln Vivo |
In vivo efficacy data for JAK/HDAC-IN-1 are not extensively detailed in the available literature. As a research compound, its therapeutic potential is primarily inferred from its potent in vitro activity. Further studies, including animal xenograft models, would be required to fully establish its in vivo antitumor efficacy, pharmacokinetic profile, and safety. The compound is intended for research use only and has not been approved for clinical applications.
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| Enzyme Assay |
For JAK kinase assays, the enzymatic activity of recombinant JAK2 is measured. The enzyme is incubated with varying concentrations of JAK/HDAC-IN-1 in a reaction buffer containing ATP and a peptide substrate. The reaction is allowed to proceed for a set time, and the level of substrate phosphorylation is measured using a fluorescence-based or radiometric method. IC50 values are calculated by fitting dose-response curves. For HDAC assays, a similar protocol is employed using a fluorogenic HDAC substrate, and the release of a fluorescent product is monitored.
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| Cell Assay |
For cellular studies, hematological cancer cell lines are cultured in RPMI-1640 medium supplemented with 10% FBS. Cells are seeded in 96-well plates and treated with varying concentrations of JAK/HDAC-IN-1 for 48-72 hours. Cell viability is assessed using MTT or CellTiter-Glo assays. Apoptosis is evaluated by Annexin V/PI staining followed by flow cytometry. Protein expression and phosphorylation (e.g., STAT3, acetylated histones) are analyzed by Western blot to confirm target engagement and downstream effects.
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| Animal Protocol |
In vivo animal experiments typically involve xenograft models where immunodeficient mice are subcutaneously implanted with hematological tumor cells. Once tumors reach a certain size, mice are randomized and treated orally or intraperitoneally with JAK/HDAC-IN-1 at various doses. Tumor growth is monitored by caliper measurements. At the end of the study, tumors are harvested for Western blot analysis to assess target modulation (e.g., JAK/STAT signaling and histone acetylation) and apoptosis markers.
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| ADME/Pharmacokinetics |
Pharmacokinetic (PK) properties for JAK/HDAC-IN-1 are not fully reported in the public domain. Based on its chemical structure as a small molecule, it is expected to have moderate oral bioavailability and tissue distribution. Its metabolism is likely mediated by hepatic CYP450 enzymes, with clearance via biliary and renal excretion. A comprehensive PK study would be needed to determine its half-life, Cmax, AUC, and other key parameters for any potential therapeutic development.
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| Toxicity/Toxicokinetics |
Toxicology data for JAK/HDAC-IN-1 are limited, as it is a research compound. In vitro cytotoxicity has been observed in cancer cell lines at effective concentrations, but specific toxicity profiles, such as LD50 or organ-specific toxicity, have not been reported. As with all research chemicals, appropriate safety precautions, including the use of personal protective equipment, should be taken during handling.
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| References |
[1]. Liang X, et al. Discovery of Novel Janus Kinase (JAK) and Histone Deacetylase (HDAC) Dual Inhibitors for the Treatment of Hematological Malignancies. J Med Chem. 2019 Apr 25;62(8):3898-3923.
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| Additional Infomation |
JAK/HDAC-IN-1 is a potent dual inhibitor of JAK2 and HDAC, with IC50 values of 4 nM and 2 nM, respectively. It also inhibits JAK1, JAK3, TYK2, HDAC2, HDAC6, and HDAC8. The compound exhibits antiproliferative and proapoptotic activities in hematological cell lines. It is a research tool for studying cancers involving JAK/STAT and HDAC pathways and is not approved for clinical use.
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| Molecular Formula |
C19H21CL2N7O2
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|---|---|
| Molecular Weight |
450.3217
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| Exact Mass |
449.113
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| CAS # |
2284621-75-4
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| PubChem CID |
138377596
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
3.3
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
10
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| Heavy Atom Count |
30
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| Complexity |
525
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=CC(=CC=C1NC2=NC(=NC=C2Cl)NC3=CN(N=C3)CCCCCC(=O)NO)Cl
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| InChi Key |
MTOQNLGMTJOJOF-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C19H21Cl2N7O2/c20-13-5-7-14(8-6-13)24-18-16(21)11-22-19(26-18)25-15-10-23-28(12-15)9-3-1-2-4-17(29)27-30/h5-8,10-12,30H,1-4,9H2,(H,27,29)(H2,22,24,25,26)
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| Chemical Name |
6-[4-[[5-chloro-4-(4-chloroanilino)pyrimidin-2-yl]amino]pyrazol-1-yl]-N-hydroxyhexanamide
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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 Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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 : ~20.83 mg/mL (~46.26 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.62 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 (4.62 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 (4.62 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 | 2.2206 mL | 11.1032 mL | 22.2064 mL | |
| 5 mM | 0.4441 mL | 2.2206 mL | 4.4413 mL | |
| 10 mM | 0.2221 mL | 1.1103 mL | 2.2206 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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