VHL and lung cancer: ACBI2 features a DC50 at 18 h of 1 nM for SMARCA2, a 30-fold selectivity for SMARCA2 over SMARCA4 degradation in several cell lines, and induced significant cytotoxicity in NCI-H1568 lung cancer cell lines (IC50 of 7 nM) and inhibition of tumour growth in mouse lung cancer xenograft models.103 The development of ACBI2, a highly potent orally available VHL-recruiting SMARCA2-selective degrader, illustrates the potential of rational, structure-based and pharmacokinetically-driven design in the development of orally administrable VHL-based PROTAC degraders with therapeutical potential.