The development of therapeutic agents for SLE based on inhibition of innate immune receptor TLR7

In this study, we evaluated the effectiveness of CB-7, a selective small molecule inhibitor of TLR7, aiming at developing therapeutic agents for systemic lupus erythematosus (SLE). CB-7 showed inhibitory activities against TLR7 in murine and human immune cells. However, the effectiveness of CB-7 in SLE model mice was not proven, and we found that CB-7 has problems in pharmacokinetics and metabolic stability. In order to solve these problems, CB-7 derivatives were synthesized. Several derivatives showed higher inhibitory activities than CB-7, and the structure-activity relationship on TLR7 inhibition was also revealed. We have already undertaken further synthesis of derivatives based on structural biology to optimize the biological activity. This will allow us to obtain a more potent TLR7 inhibitor with high metabolic stability.