KDM5B-IN-4 (compound 11ad) is a lysine demetlase 5B (KDM5B) inhibitor with an IC50 of 0.025 μM KDM5B-IN-4 increases substrate H3K4me1/2/3 level by inhibiting KDM5B in PC-3 cells. KDM5B-IN-4 downregulates PI3K/AKT. KDM5B-IN-4 reduces tumor volume in mice and shows less toxic to organs.
KDM5B-IN-4 (20 μM, 72 h) has targeted inhibition of KDM5B and induction of H3K4me1/2/3 production in PC-3 cells[1].KDM5B-IN-4 (0-20 μM; 72 h) not only targets KDM5B in cells, but also induces H3K4me1/2/3 accumulation in PC-3 cells[1]. KDM5B-IN-4 (0-10 μM, 0-24 h) inhibited the proliferation and migration of prostate cancer cells, blocked the PC-3 cycle in the G2/M phase, and induced apoptosis of PC-3 cells to a certain extent[1].
KDM5B-IN-4 (50 mg/kg, i.g., 50 mg/kg/d, 13 days) treatment at 50 mg/kg was slightly better than the efficacy of DOX[1].KDM5B-IN-4 (50 mg/kg, i.g., 50 mg/kg/d, 25 days) did not cause noticeable damage to the mice, confirming that 11ad had no significant toxicity or side effects in vivo[1].Pharmacokinetic Analysis in KDM5B-IN-4 (compound 11ad) Xenograft Model[1]KDM5B-IN-4 (compound 11ad) 药代动力学分析[1]
References:
[1]. Cao Y, et al. Discovery of a novel 1H-pyrazole- [3,4-b] pyridine-based lysine demetlase 5B inhibitor with potential anti-prostate cancer activity that perturbs the phosphoinositide 3-kinase/AKT pathway. Eur J Med Chem. 2023 May 5;251:115250.