Comparative Pharmacokinetic Properties and Antitumor Activity of the Marine HDACi Largazole and Largazole Peptide Isostere

. Author manuscript; available in PMC: 2016 Apr 1.

Published in final edited form as: Cancer Chemother Pharmacol. 2015 Jan 24;75(4):671–682. doi: 10.1007/s00280-015-2675-1

A. Calculated IC₅₀ (nM) of Largazole and Largazole Analogs in Select Cell Lines
Compound	HTC-116	HT-29	SW620	A549	MiaPaCa
Largazole	3.5	16.2	26.5	3.8	206.4
Largazole Peptide Isostere	103.3	81.0	224.8	281.2	842.7
Pyridyl Analog Depsipeptide	0.7	0.3	8.2	0.18	91.8
Pyridyl Analog Peptide Isostere	82.9	31.5	81.0	542.7	3536
Pyridyl Analog Pyridyl Disulfide	ND	ND	ND	719.4	3290

B. Calculated Inhibitory IC₅₀ (nM) of Largazole and Largazole Analogs Verses HDAC 1,2,3,6^*
Compound	HDAC 1	HDAC 2	HDAC 3	HDAC 6
Largazole Thiol	3.4	10.5	10.4	203.6
Largazole Peptide Isostere Thiol	5.8	10.0	12.0	2045
Pyridyl Analog Depsipeptide Thiol	3.9	16.5	17.9	654.5
Pyridyl Analog Peptide Isostere Thiol	38.7	76.4	82.8	33710
Pyridyl Analog Pyridyl Disulfide	ND	ND	ND	ND
Vorinostat (SAHA)	136.7	211.5	206.9	143.4

ND = not determined

All compounds tested were the unmasked thiol forms.