Table 2. Permeabilities for PROTACs 1–3^a.

PROTAC	CRBN (cell) IC50 (μM)	CRBN (bio) IC50 (μM)	CRBN, ratio cell/biob	PAMPA (−log Pe, cm/s)	Ppassivec (nm/s)
1	0.924 ± 0.119	0.244 ± 0.028	4	6.56 ± 004	30 ± 1.5
2	16.9 ± 1.41	1.41 ± 0.207	12	n.d.d	11 ± 1.7
3	18.0 ± 2.07	0.667 ± 0.066	27	>7.37	6 ± 1.4

^aThe potencies for binding to CRBN are mean values ± SEM from five or six repeats. PAMPA data are mean values ± SEM from three repeats. Permeabilities across Caco-2 cell monolayers are mean values ± SEM from two or three repeats.

^bHighly permeable PROTACs have a low cell/bio ratio, while the opposite is true for low-permeable ones.

^cPassive permeability (P_passive) across Caco-2 cell monolayers at pH 7.4 was calculated as the geometric mean of P_app AB and P_app BA (Table S1), i.e. P_passive = (P_appAB × P_appBA)^0.5.

^dNot determined.