FIGURE 1.

Identification of benzothiophene carboxylate derivatives as novel BDK inhibitors. A, candidate BDK inhibitor 476-I16 identified by high-throughput screening of a 2,000-compound chemical library. B, separation of compound 476-I16 into smaller compound fractions BT1 and BT2 by reversed-phase HPLC. C, absence of BDK inhibition by BT1. D, inhibition of BDK as a function of BT2 concentrations. E, activation of BCKDC in MEF cells by BT1, BT2, and a mixture of both from compound 476-I16, compared with the DMSO control. F, chemical structures, degradation schemes, and molecular masses (m/z) of benzothiophene carboxylate derivatives. BT3 is an analog of BT1. G, chemical structures of (S)-CPP, BT2, and BT2F. Error bars, S.D.