In contrast to
non-small cell lung cancer, there has been no significant progress in the development of
therapies for the
small cell lung cancer (SCLC) in recent decades. Although various targeted agents, including
immunotherapies, have recently been developed for testing in clinical trials, novel therapeutic agents are still needed for SCLC. We developed a potent inhibitor of
cyclin-dependent kinase 7 (CDK7), designated YPN-005, and sought to determine whether it showed any anticancer effects in SCLC cells,
cisplatin or
etoposide-resistant cells, or organoids derived from SCLC patients. In a panel of
kinases assay, YPN-005 was highly selective for CDK7 and showed antiproliferative effects in SCLC and cells with acquired resistance to conventional anticancer drugs. Similar to other CDK7 inhibitors, YPN-005 treatment significantly decreased the phosphorylation of the carboxyl-terminal domain of
RNA polymerase II. Consistent with the in vitro results, YPN-005 treatment showed a significant inhibition of
tumor growth through the suppression of
RNA polymerase II phosphorylation. Finally, YPN-005 showed potent anticancer effects in organoids derived from SCLC patients compared to another CDK7 inhibitor, THZ1. Therapeutic targeting of CDK7 in SCLC might be suitable for clinical investigation, and YPN-005 may be a promising therapeutic option for primary SCLC and SCLC with acquired resistance to conventional
therapy.