Target Validation Information
TTD ID T03691
Target Name Leukotriene A-4 hydrolase (LTA4H)
Type of Target
Successful
Drug Potency against Target DG051 Drug Info K(d) = 26 nM [7]
(4-(thiophen-2-yl)phenyl)methanamine Drug Info IC50 = 98 nM [7]
(R)-2-((4-benzylphenoxy)methyl)piperidine Drug Info IC50 = 60 nM [8]
(R)-2-((4-phenoxyphenoxy)methyl)piperidine Drug Info IC50 = 126 nM [8]
(R)-2-(4-Benzylphenoxymethyl)pyrrolidine Drug Info IC50 = 449 nM [7]
(R)-N-benzyl-4-(pyrrolidin-2-ylmethoxy)aniline Drug Info IC50 = 207 nM [6]
(R/S)-2-((4-benzylphenoxy)methyl)piperazine Drug Info IC50 = 342 nM [8]
(R/S)-2-((4-benzylphenoxy)methyl)piperidine Drug Info IC50 = 105 nM [8]
(R/S)-2-((4-phenoxyphenoxy)methyl)piperidine Drug Info IC50 = 207 nM [8]
(S)-2-((4-phenoxyphenoxy)methyl)piperidine Drug Info IC50 = 286 nM [8]
1-(4-Phenoxyphenyl)piperazine Drug Info IC50 = 1.4 nM [7]
1-(pentyloxy)-4-phenoxybenzene Drug Info IC50 = 4130 nM [3]
1-butoxy-4-phenoxybenzene Drug Info IC50 = 5720 nM [3]
1-[4-(4-Iodophenoxy)phenyl]piperazine Drug Info IC50 = 340 nM [7]
1-[4-(Benzothiazol-2-yloxy)benzyl]piperidin-4-ol Drug Info IC50 = 250 nM [2]
2-(4-benzylphenoxy)ethanamine Drug Info IC50 = 9 nM [3]
2-(4-phenoxyphenoxy)ethanamine Drug Info IC50 = 228 nM [3]
2-(4-Piperidin-1-ylmethylphenoxy)benzothiazole Drug Info IC50 = 230 nM [2]
2-(7-(benzyloxy)-1H-indol-3-yl)ethanamine Drug Info IC50 = 12500 nM [5]
2-Amino-N-[4-(phenylmethoxy)phenyl]-acetamide Drug Info IC50 = 280 nM [1]
2-[4-(2-Azepan-1-ylethoxy)phenoxy]benzooxazole Drug Info IC50 = 4 nM [2]
2-[4-(2-Azepan-1-ylethoxy)phenoxy]benzothiazole Drug Info IC50 = 66 nM [2]
2-[4-(2-Morpholin-4-ylethoxy)phenoxy]benzooxazole Drug Info IC50 = 58 nM [2]
2-[4-(2-Piperidin-1-ylethyl)phenoxy]benzothiazole Drug Info IC50 = 280 nM [2]
4-(4-(pentyloxy)phenoxy)phenol Drug Info IC50 = 2480 nM [3]
4-(4-butoxyphenoxy)phenol Drug Info IC50 = 5560 nM [3]
4-(4-propoxyphenoxy)phenol Drug Info IC50 = 5690 nM [3]
4-amino-N-[4-(benzyloxy)phenyl]butanamide Drug Info IC50 = 61 nM [1]
4-[2-(4-Benzylphenoxy)ethyl]pyridine Drug Info IC50 = 8.7 nM [7]
4S-4,5-Diamino-N-(4-phenoxyphenyl)pentanamide Drug Info IC50 = 21 nM [1]
8(S)-amino-2(R)-methyl-7-oxononanoic acid Drug Info IC50 = 300 nM [9]
JNJ-10392980 Drug Info IC50 = 51 nM [2]
N1-[4-(Phenylmethoxy)phenyl]-D-aspartamine Drug Info IC50 = 9300 nM [1]
N1-[4-(Phenylmethoxy)phenyl]-D-glutamine Drug Info IC50 = 7200 nM [1]
N1-[4-(Phenylmethoxy)phenyl]-L-aspartamine Drug Info IC50 = 5400 nM [1]
N1-[4-(Phenylmethoxy)phenyl]-L-glutamine Drug Info IC50 = 680 nM [1]
N4-[4-(Phenylmethoxy)phenyl]-L-aspartamine Drug Info IC50 = 1100 nM [1]
N5-(4-Phenoxyphenyl)-L-glutamine Drug Info IC50 = 19 nM [1]
N5-[(4-Phenoxy)-3-pyridyl]-L-glutamamide Drug Info IC50 = 2600 nM [1]
N5-[4-(1H-pyrrol-1-yl)phenyl]-L-glutamamide Drug Info IC50 = 9700 nM [1]
N5-[4-(2-methylphenoxy)phenyl]-L-glutamamide Drug Info IC50 = 2800 nM [1]
N5-[4-(2-Oxo-3-phenylpropoxy)phenyl]-L-glutamine Drug Info IC50 = 18 nM [1]
N5-[4-(2-phenylethoxy)phenyl]-L-glutamine Drug Info IC50 = 46 nM [1]
N5-[4-(3-methylphenoxy)phenyl]-L-glutamamide Drug Info IC50 = 150 nM [1]
N5-[4-(3-Phenylpropoxy)phenyl]-L-glutamine Drug Info IC50 = 31 nM [1]
N5-[4-(4-(3-Furyl)phenoxy)phenyl]-L-glutamamide Drug Info IC50 = 29 nM [1]
N5-[4-(4-methylphenoxy)phenyl]-L-glutamamide Drug Info IC50 = 13 nM [1]
N5-[4-(N-Phenylamino)phenyl]-L-glutamine Drug Info IC50 = 210 nM [1]
N5-[4-(Phenylmethoxy)phenyl]-D-glutamine Drug Info IC50 = 1600 nM [1]
N5-[4-(Phenylmethoxy)phenyl]-L-glutamamide Drug Info IC50 = 23 nM [1]
N5-[4-(Phenylmethoxy)phenyl]-L-glutamine Drug Info IC50 = 20 nM [1]
N5-[4-Benzylphenyl]-L-glutamamide Drug Info IC50 = 21 nM [1]
N6-[4-(4-methylphenoxy)phenyl]-L-homoglutamine Drug Info IC50 = 6 nM [1]
SA-6541 Drug Info IC50 = 270 nM [4]
Action against Disease Model DG051 Drug Info In preclinical studies DG051 has been shown in h uMan blood ex vivo and in animal models to be a potent inhibitor of LTB4 production. It was potent in the HWB assay with IC50 value of 37 nM. It was a potent inhibitor of LTA4H aminopeptidase activity against l-alanine p-nitroanilide (IC50 = 72 nM). [7]
References
REF 1 Synthesis of glutamic acid analogs as potent inhibitors of leukotriene A4 hydrolase. Bioorg Med Chem. 2008 May 1;16(9):4963-83.
REF 2 Identification of a potent, selective, and orally active leukotriene a4 hydrolase inhibitor with anti-inflammatory activity. J Med Chem. 2008 Jul 24;51(14):4150-69.
REF 3 Activation and inhibition of leukotriene A4 hydrolase aminopeptidase activity by diphenyl ether and derivatives. Bioorg Med Chem Lett. 2008 Dec 15;18(24):6549-52.
REF 4 Synthesis and biological evaluation of N-mercaptoacylcysteine derivatives as leukotriene A4 hydrolase inhibitors. Bioorg Med Chem Lett. 2009 Jan 15;19(2):442-6.
REF 5 Discovery of multitarget inhibitors by combining molecular docking with common pharmacophore matching. J Med Chem. 2008 Dec 25;51(24):7882-8.
REF 6 Discovery of leukotriene A4 hydrolase inhibitors using metabolomics biased fragment crystallography. J Med Chem. 2009 Aug 13;52(15):4694-715.
REF 7 Discovery of 4-[(2S)-2-{[4-(4-chlorophenoxy)phenoxy]methyl}-1-pyrrolidinyl]butanoic acid (DG-051) as a novel leukotriene A4 hydrolase inhibitor of ... J Med Chem. 2010 Jan 28;53(2):573-85.
REF 8 Discovery of novel leukotriene A4 hydrolase inhibitors based on piperidine and piperazine scaffolds. Bioorg Med Chem Lett. 2010 May 1;20(9):2851-4.
REF 9 Isolation and structure of leukotriene-A4 hydrolase inhibitor: 8(S)-amino-2(R)-methyl-7-oxononanoic acid produced by Streptomyces diastaticus. J Nat Prod. 1996 Oct;59(10):962-4.

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