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。

TK-129 is an orally active, low-toxicity, potent KDM5B inhibitor (with high affinity; IC 50 =44 nM). TK-129 exerts cardioprotective effects by inhibiting KDM5B and blocking the KDM5B -associated Wnt pathway. 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 of cardiovascular disease [1].

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.

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: 1.19 Pharmacokinetic 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 V ss (L/kg) 33.4 2.7 T 1/2 (h) 2.4 0.4 T max (h) 0.4 - C max (ng/mL) 709.7 1229.1 AUC 0-24 (ng/mL h) 1038.2 479.6 F (%) 42.37 -

C15H23N5O2

305.38

(< 1 mg/ml refers to the product slightly soluble or insoluble )
Powder: -20°C for 3 years
In solvent: -80°C for 2 years