Table 4. Physicochemical Properties and Target Degradation Capabilities of BRD4-Targeting PROTACs 43–45 and the HDAC6 Degraders 50 and 51.

PROTAC	elog D7.4a	PPB (%)b	CHIc	log(S)d	Target deg (%)e
dBET57	2.7	93	32.3	–5.3	92
MZ1	2.7	92	31.5	–4.9	94
43a	2.1	91	30.4	–4.8	70
43b	2.3	92	30.7	–4.5	85
43c	2.7	94	34.8	n.a.g	80
43d	3.3	95	38.7	n.a.	69
43e	3.8	96	43.9	n.a.	65
43f	2.2	90	29.6	–4.3	81
43g	2.3	90	28.8	–3.9	60
43h	2.5	93	32.4	–5.8	91
43j	3.1	95	36.0	n.a.	83
43k	2.9	95	36.7	n.a.	37
44h	2.4	92	31.6	–5.6	96
45h	2.2	91	30.6	–5.5	83
50	1.0	90	27.5	n.d.f	81
51	0.9	90	28.5	n.d.	87
A6	1.3	91	29.2	n.d.	72

^aDistribution coefficients at pH 7.4 were estimated by an HPLC-based method.

^bPlasma protein binding; experimentally determined percentage of compound bound to human serum albumin.

^cChromatographic hydrophobicity index values referring to IAM chromatography (CHI_IAM values).

^dLogarithm of the solubility measured in mol/L at pH 6.8 by an HPLC-based method.

^ePercentage of degraded target protein (BRD4 after 24 h treatment of MOLT4 cells with 0.1 μM of PROTACs 43–45 or HDAC6 after 24 h treatment of MM.1S cells with 0.1 μM of PROTACs 50, 51, or A6). Values are normalized to respective loading controls and to DMSO-treated conditions. BRD4/HDAC6 degradation data represent the average of at least two independent biological experiments.

^fNot determined.

^gNot available (<1 μg/mL).