5,6,8-Trichloro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid

 new CK2 inhibitor from OTAVAchemicals with IC₅₀ = 0.3 mM

Ref.: Golub et al. Evaluation of 3-Carboxy-4(1H)-quinolones as Inhibitors of Human Protein Kinase CK2. Journal of Medicinal Chemistry (2006), 49, 6443-6450
Abstract: A new class of CK2 inhibitors, 3-carboxy-4(1H)-quinolones, has been selected via receptor-based virtual screening of the OTAVAchemicals compound library. It was revealed that the most active compounds, 5,6,8-trichloro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (IC50 = 0.3 μM) and 4-oxo-1,4-dihydrobenzo[h]quinoline-3-carboxylic acid (IC50 = 1 μM), are ATP competitive (Ki values are 0.06 and 0.28 μM, resp.). Evaluation of the inhibitors on seven protein kinases shows considerable selectivity toward CK2. According to theoretical calculations and experimental data, a structural model describing the key features of 3-carboxy-4(1H)-quinolones responsible for tight binding to CK2 active site has been developed.