TK-129

• CAT Number: I042815
• CAS Number: 3031476-73-7
• Molecular Formula: C15H23N5O2
• Molecular Weight: 305.38
• Purity: ≥95%
• Synonyms: 1-cyclopropyl-3-[(3R)-1-(5-propan-2-yl-1H-pyrazole-3-carbonyl)pyrrolidin-3-yl]urea
• InChI: InChI=1S/C15H23N5O2/c1-9(2)12-7-13(19-18-12)14(21)20-6-5-11(8-20)17-15(22)16-10-3-4-10/h7,9-11H,3-6,8H2,1-2H3,(H,18,19)(H2,16,17,22)/t11-/m1/s1
• InChIKey: WNSMPEBHTSITSG-LLVKDONJSA-N
• SMILES: CC(C)C1=CC(=NN1)C(=O)N2CCC(C2)NC(=O)NC3CC3

TK-129 is an orally active, low-toxicity, potent KDM5B inhibitor (with high affinity; IC50=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].
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].

Reference

[1]. Tang K, et al. Discovery of Novel Pyrazole-Based KDM5B Inhibitor TK-129 and Its Protective Effects on Myocardial Remodeling and Fibrosis. J Med Chem. 2022 Sep 16.
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