TK-129 是一种口服有效的、低毒的强效KDM5B抑制剂 (具有高亲和力;IC50=44 nM)。TK-129 通过抑制KDM5B和阻断KDM5B相关的Wnt通路，来发挥心脏保护作用。TK-129 能在体外减少 Ang II 诱导的心脏成纤维细胞的活化，并在体内减少异丙肾上腺素诱导的心肌重塑和纤维化。TK-129 可用于心血管疾病的研究。
| 生物活性 | TK-129 is an orally active, low-toxicity, potent KDM5B inhibitor (with high affinity;IC50=44 nM). TK-129 exerts cardioprotective effects by inhibitingKDM5Band blocking theKDM5B-associatedWntpathway. TK-129 reduces ang II-induced activation of cardiac fibroblasts in vitro and reduces isoprenaline-induced myocardial remodelling and fibrosis in vivo. TK-129 can be used in studies ofcardiovascular disease[1]. |
| IC50& Target[1] | |
体外研究
(In Vitro) | TK-129 mediates inhibition of KDM5B activity significantly reduces the activation, migration, and proliferation of myofibroblasts induced by Ang II in vitro[1].
TK-129 (10 μM; 48 h) shows low cytotoxicity in NRCFs and NRCMs[1].
TK-129 (0.1, 0.2, 0.3, 0.4, 0.5 μM; 48 h) can engage toand inhibit KDM5B activity in NRCFs[1].
Cell Cytotoxicity Assay[1] | Cell Line: | NRCFs and NRCMs | | Concentration: | 10 μM | | Incubation Time: | 48 h | | Result: | Exhibited the cell survival rates were almost more than 90%. |
Western Blot Analysis[1] | Cell Line: | NRCFs | | Concentration: | 0.1, 0.2, 0.3, 0.4, 0.5 μM | | Incubation Time: | 48 h | | Result: | Increased the expression level of KDM5B substrate H3K4me3 protein in a concentration-dependent manner. |
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体内研究
(In Vivo) | TK-129 (2 g/kg; p.o.; single) shows good bio-safety in mice[1].
TK-129 (50 mg/kg; p.o.; twice daily for 24 days) effectively reduces isoproterenol-induced pathological myocardial remodeling in vivo[1].
TK-129 (2 or 10 mg/kg; i.v. or p.o.; single) demonstrates favorable PK properties in vivo[1].
| Animal Model: | Wild C57BL/6 mice (8 to 10-week-old; half male and half female)[1]. | | Dosage: | 2 g/kg | | Administration: | Oral gavage, single. | | Result: | Exhibited all mice in the acute toxicity group survived and gained weight normally, after 2 weeks. |
| Animal Model: | C57BL/6 mice (isoproterenol (ISO)-induced)[1]. | | Dosage: | 50 mg/kg | | Administration: | Oral gavage, twice daily for 24 days. | | Result: | Alleviated myocardial remodeling induced by ISO in vivo. |
| Animal Model: | Male SD Rats (223.5-265.1 g)[1]. | | Dosage: | 2 mg/kg (for i.v.); 10 mg/kg (for p.o.). | | Administration: | Intravenous injection or oral gavage; single. | | Result: | 1.19Pharmacokinetic 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/mLoh) | 1038.2 | 479.6 | | F (%) | 42.37 | - |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | Please store the product under the recommended conditions in the Certificate of Analysis. |
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