TABLE 2

Inhibitors of H2S synthesizing enzymes

For CBS and CSE that catalyze multiple reactions reported IC50 values correspond to reactions generating H2S. L-cysteine was used as a substrate for CSE and L-cysteine/homocysteine were used for CBS. SAM was sometimes included in CBS activity assays. The recombinant CBS and CSE enzymes used were human in the majority of the cases; the enzymes carried tags for purification purposes or were modified (truncated) to increase yield/activity. For most of the 3-MST measurements the murine enzyme was used.

Inhibitor structureChemical or common nameIC50 recombinant CSEIC50 recombinant CBSIC50 recombinant 3-MSTSelectivityReference
Embedded ImageAminoethoxyvinyl glycine (AVG)1.0 μM1No inhibition up to 1 mM1No inhibition at 1 mM2CSE >>>CBS1Asimakopoulou et al., 2013
2Unpublished observations
Embedded ImagePropargylglycine (PAG)40.0 μM1No inhibition up to 10 mM1No inhibition at 10 mM5CSE>>>CBS1Asimakopoulou et al., 2013
42.2 μM2No inhibition up to 2 mM42Corvino et al., 2016
200 μM33Sun et al., 2009
1 μM or 26 µM44Zhou et al., 2013
5Unpublished observations
Embedded Imageβ-cyano-alanine (BCA)14.0 μM (CSE)40% inhibition at 10 mM15% inhibition at 10 mM2CSE>>CBS1Asimakopoulou et al., 2013
2Unpublished observations
Embedded ImageAminooxyacetic acid (AOAA)1.1 μM18.5 μM1No inhibition at 50 μM4CSE>CBS1Asimakopoulou et al., 2013
2 μM22Chao et al., 2016
3 μM33Druzhyna et al., 2016
4Unpublished observations
Embedded ImageD-Penicillamine (D-pen)270 μM8.5 mMNot testedCSE>CBS (effect on 3-MST not known)Brancaleone et al., 2016
Embedded ImageHydroxylamine4.8 μM278 μM1No inhibition at 50 μM3CSE>CBS1Asimakopoulou et al., 2013
20, 250, or 400 µM22Zhou et al., 2013
3Unpublished observations
Embedded ImageTrifluoroalanine289 μM66 μMNot testedCBS>CSE (effect on 3-MST not known)Asimakopoulou et al., 2013
Embedded ImageBenserazide16% inhibition at 100 μM130 μM150% inhibition at 300 μM1CBS > CSE>3-MST1Druzhyna et al., 2016
125 μM (IC25) 22Thorson et al., 2013
Embedded Image2,3,4-trihydroxybenzylhydrazine (THBH or Ro 04-5127)Not tested30 μMNot testedCBS (effect on CSE or 3-MST not known)Druzhyna et al., 2016
Embedded Image1,6-dimethyl-pyrimido[5,4-e]-1,2,4-triazine-5,7(1H,6H)-dione(NSC 67078)30 µM112 µM1Not testedCBS>CSE (effect on 3-MST not known)1Zhou et al., 2013
1 µM22Druzhyna et al., 2016
Embedded ImageNSC110412.5 µM4 µMNot testedCSE≥CBS (effect on 3-MST not known)Zhou et al., 2013
Embedded ImageJHU-855525 µM8 - 12 µMNot testedCBS≥CSE (effect on 3-MST not known)Zhou et al., 2013
Embedded ImageMBSEW03275200 µM15 µMNot testedCBS>CSE (effect on 3-MST not known)Zhou et al., 2013
Embedded ImageSP1431100840 µM20 µMNot testedCBS≥CSE (effect on 3-MST not known)Zhou et al., 2013
Embedded ImageAurintricarboxynic acidNot tested3 µM2Not testedCBS (effect on CSE or 3-MST not known)Druzhyna et al., 2016
Embedded Image1,4 NaphtoquinoneNot tested35 µMNot testedCBS (effect on CSE or 3-MST not known)Thorson et al., 2013
Embedded Image2,4-DinitrophenolNot tested56 µMNot testedCBS (effect on CSE or 3-MST not known)Thorson et al., 2013
Embedded ImagePiperineNot tested61 µMNot testedCBS (effect on CSE or 3-MST not known)Thorson et al., 2013
Embedded ImageApigeninNot tested83 µMNot testedCBS (effect on CSE or 3-MST not known)Thorson et al., 2013
Embedded ImageAmilorideNot tested89 µMNot testedCBS (effect on CSE or 3-MST not known)Thorson et al., 2013
Embedded ImageFraxetinNot tested134 µMNot testedCBS (effect on CSE or 3-MST not known)Thorson et al., 2013
Embedded ImageMNP2-A6Not tested83 µMNot testedCBS (effect on CSE or 3-MST not known)Thorson et al., 2015
Embedded ImageMNP2-B7Not tested87 µMNot testedCBS (effect on CSE or 3-MST not known)Thorson et al., 2015
Embedded Image2-Oxo-N-(prop-2-yn-1-yl) thiazolidine-4-carboxamide(SHIP-2a)6.3 μMNot testedNot testedCSE (effect on CSE or 3-MST not known)Corvino et al., 2016
Embedded Image2-(2-((4-Oxo-3,4-dihydroquinazolin-2-yl)thio)acetamido)thiophene-3-carboxamide (Compound 1 or I3MT-1a)25% inhibition at 100 μM25% inhibition at 100 μM1.7 μM3-MSTHanaoka et al., 2017
Embedded Image2-((2-(2,4-Dihydroxyphenyl)-2-oxoethyl)thio)-5,6-dimethylthieno[2,3-dl]pyrimidin-4(3H)-oneInconclusive due to technical issuesInconclusive due to technical issues6.3 μM3-MST (effect on CSE or CBS not clear)Hanaoka et al., 2017
(Compound 2 I3MT-2a)
Embedded Image(2-4-Hydroxy-6-methylpyrimidin-2-yl-sulfanyl-1-naphthalen-1-yl-ethan-1-one)No inhibition at 100 μMNo inhibition at 100 μM2.7 μM3-MSTHanaoka et al., 2017
(Compound 3 or I3MT-3a)
Embedded Image3-(Phenylsulfonamido) benzoic acid25% inhibition at 100 μMEnhancement of activity5.7 μM3-MSTHanaoka et al., 2017
(Compound 5 or I3MT-5a)
  • a Name communicated by author after the publication.