LDC4297 hydrochloride

LDC-4297 is an inhibitor of cyclin-dependent kinase 7 (CDK7; IC₅₀ = <5 nM).¹ It is selective for CDK7 over CDK4, CDK6, and CDK9 (IC₅₀s = >10, >10, and 1.71 μM), however, it also inhibits CDK2 and CDK1 (IC₅₀s = 6.4 and 53.7 nM, respectively). LDC-4297 (10-100 nM) induces apoptosis in A549, HeLa, and HCT116 cancer cells in a concentration-dependent manner. It inhibits human cytomegalovirus (HCMV) replication in human fibroblasts (EC₅₀ = 24.5 nM).² LDC-4297 also reduces replication of Herpesviridae, Adenoviridae, Poxviridae, Retroviridae, and Orthomyxoviridae family viruses (EC₅₀s = 0.02-1.13 μM).

1.Kelso, T.W.R., Baumgart, K., Eickhoff, J., et al.Cyclin-dependent kinase 7 controls mRNA synthesis by affecting stability of preinitiation complexes, leading to altered gene expression, cell cycle progression, and survival of tumor cellsMol. Cell. Biol.34(19)3675-3688(2014) 2.Hutterer, C., Eickhoff, J., Milbradt, J., et al.A novel CDK7 inhibitor of the pyrazolotriazine class exerts broad-spectrum antiviral activity at nanomolar concentrationsAntimicrob. Agents Chemother.59(4)2062-2071(2015)