Until recently, however, it has remained challenging to develop indisulam-based DCAF15-recruiting PROTACs,76,77 most likely because of the weak binding affinities of these compounds to DCAF15 alone, or perhaps due to unsuitable orientation between the binding pocket of sulfonamides and the RING domain of CUL4.74 In 2020, Li et al. reported a first aryl sulfonamide–based PROTAC, DP1 (Fig. 5B), that induces degradation of BRD4 and shows tumor growth inhibitory activity in mouse models in vivo. The gene discussed is DCAF15; the disease is neoplasm.