To investigate the on-target engagement of HY041004 in cancer cells, we also conducted cellular thermal shift assay.31 Compared with the DMSO control, HY041004 stabilized JOSD2 at denaturation temperatures ranging from 37.0 °C to 53.4 °C, which demonstrated the interaction of HY041004 and JOSD2 (Fig. 7f). Here, JOSD2 is linked to cancer.