Development of Dimethylisoxazole-Attached Imidazo[1,2-<i>a</i>]pyridines as Potent and Selective CBP/P300 Inhibitors
Alex Muthengi, Virangika K. Wimalasena, Hailemichael O. Yosief, Melissa J. Bikowitz, Logan H. Sigua, Tingjian Wang, Deyao Li, Zied Gaieb, Gagan Dhawan, Shuai Liu, Jon A. Erickson, Rommie E. Amaro, E. Schönbrunn, Jun Qi, Wei Zhang
Abstract
5193 nM). The SAR we established is in good agreement with literature-reported CBP inhibitors, such as CBP30, and demonstrates the advantage of utilizing our two-step approach for inhibitor development of other bromodomains.
Topics & Concepts
BromodomainBRD4ChemistrySmall moleculeEpigeneticsDrug discoveryBET inhibitorBinding siteAcetylationComputational biologyBiochemistryCombinatorial chemistryBiologyGeneProtein Degradation and InhibitorsMultiple Myeloma Research and TreatmentsHistone Deacetylase Inhibitors Research