Transcriptomics profiling of ccc_R08 for mechanism-of-action investigation with forward pharmacology

To investigate the mode of action of ccc_R08, a first-in-class orally available HBV cccDNA inhibitor, we designed and implemented two orthogonal and complementary approaches: a forward pharmacology approach and a reverse pharmacology approach. Bioinformatics analysis integrating biological knowledge with the observations from both approaches offered us preliminary insights into the mode of action of ccc_R08. Overall design: In the forward pharmacology approach, we characterized the transcriptome profiles of HBV-infected PHH treated with the active compound ccc_R08, a less active compound ccc_R07 derived from the same chemical series with an identical backbone and with side-chain modifications, and DMSO as control.