. Author manuscript; available in PMC: 2019 Mar 15.

Published in final edited form as: J Med Chem. 2017 Jun 27;60(13):5816–5825. doi: 10.1021/acs.jmedchem.7b00514

Table 1. IC₅₀ and K_i Values and Selectivity Data for 5 and 10a–f.

				IC₅₀(nM)^a
	R-NH₂	Inhibitor Type	K_i (nM) MMP-13	MMP-13	MMP-1	MMP-2	MMP-8	MMP-9	MMP-14
5	–		800	2400	-^b	-^b	-^b	-^b	-^b
(S)-10a		Zn²⁺ chelator	2.3	2.2±0.8	-^c	-^c	-^c	-^c	-^c
(R)-10a		Zn²⁺ chelator	1.6	7.0±1.2	-^c	-^c	-^c	-^c	-^c
10b		Zn²⁺ chelator	1.8	1.6	-^c	-^c	-^c	-^c	-^c
10c		non-chelator	9.2±2.0	12.0±2.2	4000	>5000	>5000	>10000	>10000
10d		non-chelator	13.5±37	3.4±0.4	>5000	730	600	>10000	>10000
10e		non-chelator	-	17.9±1.2	>10000	2700	3500	>10000	>10000
10f		non-chelator	-	16.9±1.0	>10000	>10000	>10000	>10000	>10000

The IC₅₀ values were determined by using fluorescence resonance energy transfer triple-helical peptides (fTHP) as substrates in the enzyme assay.²⁴,³⁰,³¹

Compound 5 was tested against MMP-1, -2, -8, -9, and -14 at a single concentration and these data are reported in ref 28 (Roth et al.).

Because (S)-10a, (R)-10a, and 10b are expected to be Zn-chelating agents, these were only tested at a single concentration; these data are reported in Supporting Information, Figure S1. Determination of inhibition constants and modalities were conducted by incubating the range of fTHP-15 substrate concentrations (2–25 μM) with 4 nM MMP-13 at room temperature in the presence of varying concentrations of inhibitors (0.5–50 nM). Experiments were performed 1–3 times in duplicates or triplicates.

Table 1. IC50 and Ki Values and Selectivity Data for 5 and 10a–f.

Table 1. IC₅₀ and K_i Values and Selectivity Data for 5 and 10a–f.