| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| 50mg |
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| Other Sizes |
| Targets |
KDM5 44 nM (IC50)
TK-129 targets KDM5B (lysine-specific demethylase 5B). It is a potent inhibitor with an IC50 of 44 nM. By inhibiting KDM5B, it blocks the KDM5B-associated Wnt pathway. KDM5B is also known as JARID1B. |
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| ln Vitro |
In vitro Ang II-induced myofibroblast activation, migration, and proliferation are dramatically reduced by TK-129-mediated reduction of KDM5B activity[1]. Low cytotoxicity of TK-129 (10 μM; 48 h) is observed in NRCFs and NRCMs[1]. KDM5B activity in NRCFs can be engaged and inhibited by TK-129 (0.1, 0.2, 0.3, 0.4, and 0.5 μM; 48 hours)[1].
In vitro, TK-129 (IC50=44 nM) reduces Ang II-induced cardiac fibroblast activation. It is a potent KDM5B inhibitor. Its activity has been confirmed in homogeneous time-resolved fluorescence assay (HTRF). |
| ln Vivo |
In mice, TK-129 (2 g/kg; po; single) has good biosafety[1]. Effectively reducing isoproterenol-induced pathological cardiac remodeling in vivo is TK-129 (50 mg/kg; po; twice daily for 24 days)[1]. In vivo, TK-129 (2 or 10 mg/kg; iv or po; single) exhibits advantageous PK characteristics[1].
In vivo, TK-129 reduces isoprenaline-induced myocardial remodeling and fibrosis. It exerts cardioprotective effects by inhibiting KDM5B and blocking the KDM5B-associated Wnt pathway. |
| Enzyme Assay |
Non-cellular enzyme assays for TK-129 involve measuring its inhibitory activity against KDM5B. The compound is incubated with the enzyme and a substrate, and the inhibition of demethylase activity is quantified to determine the IC50 value.
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| Cell Assay |
Cell Cytotoxicity Assay[1]
Cell Types: NRCFs and NRCMs Tested Concentrations: 10 μM Incubation Duration: 48 h Experimental Results: demonstrated the cell survival rates were almost more than 90%. Western Blot Analysis[1] Cell Types: NRCFs Tested Concentrations: 0.1, 0.2, 0.3, 0.4, 0.5 μM Incubation Duration: 48 h Experimental Results: Increased the expression level of KDM5B substrate H3K4me3 protein in a concentration-dependent manner. In vitro cellular assays for TK-129 are performed using cardiac fibroblasts. Cells are treated with the compound, and its ability to reduce Ang II-induced cardiac fibroblast activation is assessed by measuring markers of fibrosis and inflammation. |
| Animal Protocol |
Animal/Disease Models: Wild C57BL/6 mice (8 to 10weeks old; half male and half female)[1].
Doses: 2 g/kg Route of Administration: po (oral gavage), single. Experimental Results: demonstrated all mice in the acute toxicity group survived and gained weight normally, after 2 weeks. Animal/Disease Models: C57BL/6 mice ( isoproterenol (ISO)-induced)[1]. Doses: 50 mg/kg Route of Administration: po (oral gavage), twice (two times) daily for 24 days. Experimental Results: Alleviated myocardial remodeling induced by ISO in vivo. Animal/Disease Models: Male SD Rats (223.5-265.1 g )[1]. Doses: 2 mg/kg (for iv); 10 mg/kg (for po). Route of Administration: intravenous (iv) injection or po (oral gavage); single. Experimental Results: 1.19 pharmacokinetic/PK Parameters of TK-129 in Male SD Rats[1 ]. PO (10 mg/kg) IV (2 mg/kg) CL (L/h/kg) 9.9 4.2 Vss (L/kg) 33.4 2.7 T1/2 (h) 2.4 0.4 Tmax (h) 0.4 - Cmax ( ng/mL) 709.7 1229.1 AUC0-24 (ng/mL·h) 1038.2 479.6 F (%) 42.37 - In vivo animal experiments for TK-129 are conducted in animal models of cardiac remodeling and fibrosis, such as isoprenaline-induced models. The compound is administered via oral gavage, and endpoints include assessment of myocardial remodeling, fibrosis, and cardiac function. |
| ADME/Pharmacokinetics |
TK-129 has a molecular weight of 305.38. Its CAS number is 3031476-73-7. It is an orally active compound that appears as a solid and should be stored at -20°C.
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| Toxicity/Toxicokinetics |
Toxicological data for TK-129 indicate that it has low toxicity. Specific details on its safety profile are not provided in the search results. It is an orally bioavailable compound.
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| References | |
| Additional Infomation |
TK-129 is an orally bioavailable, low-toxicity, and potent KDM5B inhibitor with an IC50 of 44 nM. It exerts cardioprotective effects by inhibiting KDM5B and blocking the KDM5B-associated Wnt pathway. It is a research compound for cardiovascular disease research.
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| Molecular Formula |
C15H23N5O2
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|---|---|
| Molecular Weight |
305.38
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| CAS # |
3031476-73-7
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| Appearance |
White to off-white solid powder
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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 :~100 mg/mL (~327.46 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (8.19 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 25.0 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: ≥ 2.5 mg/mL (8.19 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 25.0 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: ≥ 2.5 mg/mL (8.19 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 | 3.2746 mL | 16.3730 mL | 32.7461 mL | |
| 5 mM | 0.6549 mL | 3.2746 mL | 6.5492 mL | |
| 10 mM | 0.3275 mL | 1.6373 mL | 3.2746 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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