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

IC50(nM)a
R-NH2 Inhibitor Type Ki (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 graphic file with name emss-82051-i001.jpg Zn2+ chelator 2.3 2.2±0.8 -c -c -c -c -c
(R)-10a graphic file with name emss-82051-i002.jpg Zn2+ chelator 1.6 7.0±1.2 -c -c -c -c -c
10b graphic file with name emss-82051-i003.jpg Zn2+ chelator 1.8 1.6 -c -c -c -c -c
10c graphic file with name emss-82051-i004.jpg non-chelator 9.2±2.0 12.0±2.2 4000 >5000 >5000 >10000 >10000
10d graphic file with name emss-82051-i005.jpg non-chelator 13.5±37 3.4±0.4 >5000 730 600 >10000 >10000
10e graphic file with name emss-82051-i006.jpg non-chelator - 17.9±1.2 >10000 2700 3500 >10000 >10000
10f graphic file with name emss-82051-i007.jpg non-chelator - 16.9±1.0 >10000 >10000 >10000 >10000 >10000
a

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

b

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.).

c

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.