Table 1. Activities of the CRBN-addressing CDK4/6d.

Cmpd	Linker	R	elog D7.4 a	D CDK4 b	D CDK6 b	c	D IKZF1 d
				0.1 μM	0.1 μM	0.1 μM	0.1 μM
3 (POM)	—	—	n.d e	91	91	n.d.	17
8 (BSJ-03-123)	—	—	2.5	27	5.5	4.9	82
11		H	3.4	25	11	2.3	1.0
12		H	2.8	19	8.4	2.3	0.8
13		H	2.8	15	7.7	1.9	1.0
14		H	3.1	26	7.8	3.3	0.8
15		H	3.1	91	65	1.4	56
16		H	4.6	76	32	2.4	6.7
17		H	5.2	86	51	1.7	18
18		H	4.4	57	17	3.4	5.9
19		H	5.4	>95	51	n.d.	35
20		H	3.7	86	16	5.4	5.8
21		Me	3.6	95	>95	n.d.	93

^aExperimental distribution coefficient at pH 7.4.

^bCDK4 or CDK6 degradation indicated as remaining CDK4 or CDK6 levels after 16 h treatment of each compound at the indicated concentration. Percentage values are normalized to DMSO-treated MM.1S cells and the respective loading controls (100%). All of the data were the average of at least three independent experiments.

^cSelectivity ratio for the degradation of CDK6 over CDK4.

^dNeosubstrate degradation indicated as remaining IKZF1 levels, respectively.

^eNot determined.