Overview on physicochemical properties as well as BRAF^V600E degradation potencies of a PLX4032-based PROTAC and paradox-breaking PROTACs 25 and 26.

Cmpd	R1	R2	X	TPSAa	elog Db	%PPBc	D BRAF d
SJF-0628		H	CH	247	2.9	96%	46%
25 (CST905)		H	CH	250	3.2	96%	52%
26		Me	N	276	3.2	96%	>95%

^aTopological polar surface area given in Ų.

^bExperimental distribution coefficient at pH 7.4.²³

^cProtein binding values were estimated by an HPLC-based method.²⁴

^dDegradation indicated as remaining BRAF^V600E levels after 4 h treatment with 1 μM of each compound (as determined by densitometric analysis of Western blot assays).