KDM5A-IN-1

• CAT Number: I002444
• CAS Number: 1905481-36-8
• Molecular Formula: C15H22N4O2
• Molecular Weight: 290.36
• Purity: ≥95%
• Synonyms: N-[(3R)-1-(5-propan-2-yl-1H-pyrazole-3-carbonyl)pyrrolidin-3-yl]cyclopropanecarboxamide
• InChI: InChI=1S/C15H22N4O2/c1-9(2)12-7-13(18-17-12)15(21)19-6-5-11(8-19)16-14(20)10-3-4-10/h7,9-11H,3-6,8H2,1-2H3,(H,16,20)(H,17,18)/t11-/m1/s1
• InChIKey: CXEXTVGTDZRKJS-LLVKDONJSA-N
• SMILES: CC(C)C1=CC(=NN1)C(=O)N2CCC(C2)NC(=O)C3CC3

KDM5A-IN-1 is a potent, orally bioavailable pan-histone lysine demethylases 5 (KDM5) inhibitor with IC50s of 45 nM, 56 nM and 55 nM for KDM5A, KDM5B and KDM5C, respectively, and with an EC50 value of 960 nM for PC9 H3K4Me3. KDM5A-IN-1 is significantly less potent against other KDM5B enzymes (1A, 2B, 3B, 4C, 6A, 7B)[1].
KDM5A-IN-1 (Compound 50, 5 mg/kg; oral administration; female CD-1 mice) treatment shows moderate clearance (28 mL/min/kg) in mice with good oral bioavailability (F% 34) and remarkably low plasma protein binding in mice (40%), with t1/2 of 0.4 hours[1].

Reference

[1]. Liang J, et al. From a novel HTS hit to potent, selective, and orally bioavailable KDM5 inhibitors. Bioorg Med Chem Lett. 2017 Jul 1;27(13):2974-2981.
 [Content Brief]