TABLE 1.

Enzymatic and cellular activities of compounds. ^{a , b}

Cmpd	Cn	R1	R2	Enzymatic IC50 (nM)			Cellular IC50 (μM)
				BRAFV600E	HDAC1	HDAC6	HCT116	HT-29
Vorinostat			NA	50.30	24.09	0.68	3.10
Dabrafenib			1.11	NA	NA	>10	0.21
14a	5	t-Butyl	2,6-Difluorophenyl	3.25	678.50	1211.07	3.00	1.00
14b	6	t-Butyl	2,6-Difluorophenyl	1.71	493.95	49.20	1.68	0.31
14c	7	t-Butyl	2,6-Difluorophenyl	2.27	312.14	127.92	4.47	0.88
14d	8	t-Butyl	2,6-Difluorophenyl	3.82	765.39	321.80	3.66	0.48
14e	6	Methyl	2,6-Difluorophenyl	3.50	42.25	14.60	7.53	6.39
14f	6	Ethyl	2,6-Difluorophenyl	1.66	61.30	26.50	4.27	1.27
14g	6	i-Propyl	2,6-Difluorophenyl	1.51	129.8	30.01	2.68	0.99
14h	6	Cyclopropyl	2,6-Difluorophenyl	1.31	49.84	27.10	4.71	2.21
14i	6	n-Propyl	2,6-Difluorophenyl	1.07	104.50	64.60	3.08	0.97
14j	6	Phenyl	2,6-Difluorophenyl	5.14	15.59	140.20	1.08	0.95
21a	6	t-Butyl	Methyl	1.03	112.55	22.17	8.52	5.02
21b	6	t-Butyl	n-Propyl	1.71	432.07	72.07	5.44	0.78
21c	6	t-Butyl	Phenyl	1.26	474.40	100.70	2.06	0.11
21d	6	Methyl	Methyl	258.00	71.04	21.81	>10	>10
21e	6	Methyl	Ethyl	107.49	52.25	18.82	9.15	>10
21f	6	Methyl	Phenyl	3.92	49.43	18.68	4.41	4.96

^aKinase activity assays were performed by a FRET-based Z′-Lyte assay.

^bAntiproliferative activities were evaluated using a CCK-8, assay. Data are means of three independent experiments.