Detailed information for compound 322710

Basic information

Technical information
  • TDR Targets ID: 322710
  • Name: N-hydroxy-1-methyl-2-[[4-[(2-methylquinolin-4 -yl)methoxy]phenyl]sulfonylmethyl]pyrrolidine -3-carboxamide
  • MW: 469.553 | Formula: C24H27N3O5S
  • H donors: 2 H acceptors: 5 LogP: 2.32 Rotable bonds: 8
    Rule of 5 violations (Lipinski): 1
  • SMILES: ONC(=O)C1CCN(C1CS(=O)(=O)c1ccc(cc1)OCc1cc(C)nc2c1cccc2)C
  • InChi: 1S/C24H27N3O5S/c1-16-13-17(20-5-3-4-6-22(20)25-16)14-32-18-7-9-19(10-8-18)33(30,31)15-23-21(24(28)26-29)11-12-27(23)2/h3-10,13,21,23,29H,11-12,14-15H2,1-2H3,(H,26,28)
  • InChiKey: QPQUYVHWOXJEPM-UHFFFAOYSA-N  


Substructure search Similarity search

Network

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Synonyms

  • 1-methyl-2-[[4-[(2-methyl-4-quinolyl)methoxy]phenyl]sulfonylmethyl]pyrrolidine-3-carbohydroxamic acid
  • 1-methyl-2-[[4-[(2-methyl-4-quinolyl)methoxy]phenyl]sulfonylmethyl]-3-pyrrolidinecarbohydroxamic acid

Targets

Known targets for this compound

Species Target name Source Bibliographic reference
Sus scrofa ADAM17 Starlite/ChEMBL References
Homo sapiens matrix metallopeptidase 1 (interstitial collagenase) Starlite/ChEMBL References
Homo sapiens matrix metallopeptidase 9 (gelatinase B, 92kDa gelatinase, 92kDa type IV collagenase) Starlite/ChEMBL References
Homo sapiens matrix metallopeptidase 13 (collagenase 3) Starlite/ChEMBL References
Homo sapiens matrix metallopeptidase 2 (gelatinase A, 72kDa gelatinase, 72kDa type IV collagenase) Starlite/ChEMBL References
Homo sapiens ADAM metallopeptidase domain 17 Starlite/ChEMBL References

Predicted pathogen targets for this compound

By orthology
Species Potential target Known druggable target/s Ortholog Group
Echinococcus multilocularis adam 17 protease Get druggable targets OG5_132656 All targets in OG5_132656
Echinococcus granulosus adam 17 protease Get druggable targets OG5_132656 All targets in OG5_132656
Schistosoma japonicum ko:K06059 a disintegrin and metalloproteinase domain 17, putative Get druggable targets OG5_132656 All targets in OG5_132656
Echinococcus granulosus Blood coagulation inhibitor Disintegrin Get druggable targets OG5_132656 All targets in OG5_132656
Loa Loa (eye worm) hypothetical protein Get druggable targets OG5_132656 All targets in OG5_132656
Schistosoma mansoni ADAM17 peptidase (M12 family) Get druggable targets OG5_132656 All targets in OG5_132656
Echinococcus multilocularis Blood coagulation inhibitor, Disintegrin Get druggable targets OG5_132656 All targets in OG5_132656
By sequence similarity to non orthologous known druggable targets
Species Potential target Known druggable target Length Alignment span Identity
Plasmodium yoelii A/G-specific adenine glycosylase, putative ADAM17   112 aa 109 aa 24.8 %
Trypanosoma congolense hypothetical protein, conserved ADAM17   112 aa 100 aa 29.0 %
Onchocerca volvulus Putative glutaminase 3 ADAM17   112 aa 105 aa 45.7 %
Brugia malayi Matrixin family protein matrix metallopeptidase 1 (interstitial collagenase) 403 aa 401 aa 27.7 %
Echinococcus granulosus matrix metallopeptidase 7 M10 family matrix metallopeptidase 13 (collagenase 3) 471 aa 448 aa 34.1 %
Brugia malayi Disintegrin family protein ADAM metallopeptidase domain 17 824 aa 724 aa 27.4 %
Echinococcus granulosus disintegrin and metalloproteinase ADAM17   112 aa 99 aa 42.4 %
Onchocerca volvulus ADAM17   112 aa 98 aa 41.8 %
Echinococcus multilocularis disintegrin and metalloproteinase ADAM17   112 aa 99 aa 42.4 %
Obtained from network model

Ranking Plot

Putative Targets List

Species Potential target Raw Global Species
Mycobacterium ulcerans thymidylate synthase 0.1029 0.62 1
Echinococcus multilocularis dihydrofolate reductase 0.042 0.0682 0.11
Plasmodium vivax bifunctional dihydrofolate reductase-thymidylate synthase, putative 0.1449 1 0.5
Echinococcus granulosus adam 17 protease 0.0802 0.4145 0.6686
Brugia malayi hypothetical protein 0.049 0.1315 0.1835
Schistosoma mansoni dihydrofolate reductase 0.042 0.0682 0.0777
Echinococcus multilocularis adam 17 protease 0.078 0.3944 0.6361
Echinococcus granulosus dihydrofolate reductase 0.042 0.0682 0.11
Mycobacterium leprae PROBABLE THYMIDYLATE SYNTHASE THYA (TS) (TSASE) 0.1029 0.62 1
Loa Loa (eye worm) thymidylate synthase 0.1029 0.62 1
Brugia malayi Dihydrofolate reductase 0.042 0.0682 0.0777
Mycobacterium tuberculosis Hypothetical protein 0.049 0.1315 0.1148
Brugia malayi thymidylate synthase 0.1029 0.62 1
Loa Loa (eye worm) hypothetical protein 0.0763 0.3784 0.5622
Echinococcus multilocularis thymidylate synthase 0.1029 0.62 1
Schistosoma mansoni ADAM17 peptidase (M12 family) 0.078 0.3944 0.6229
Mycobacterium tuberculosis Probable thymidylate synthase ThyA (ts) (TSASE) 0.1029 0.62 1
Echinococcus granulosus a disintegrin and metalloproteinase with 0.0368 0.0217 0.035
Trichomonas vaginalis conserved hypothetical protein 0.049 0.1315 0.5
Echinococcus granulosus thymidylate synthase 0.1029 0.62 1
Onchocerca volvulus 0.1029 0.62 0.5
Trypanosoma brucei dihydrofolate reductase-thymidylate synthase 0.1449 1 0.5
Schistosoma mansoni bifunctional dihydrofolate reductase-thymidylate synthase 0.1029 0.62 1
Trypanosoma cruzi dihydrofolate reductase-thymidylate synthase 0.1449 1 1
Echinococcus granulosus Blood coagulation inhibitor Disintegrin 0.0434 0.081 0.1307
Chlamydia trachomatis dihydrofolate reductase 0.042 0.0682 0.5
Brugia malayi dihydrofolate reductase family protein 0.042 0.0682 0.0777
Plasmodium falciparum bifunctional dihydrofolate reductase-thymidylate synthase 0.1449 1 0.5
Echinococcus multilocularis Blood coagulation inhibitor, Disintegrin 0.0434 0.081 0.1307
Echinococcus multilocularis a disintegrin and metalloproteinase with 0.0368 0.0217 0.035
Toxoplasma gondii bifunctional dihydrofolate reductase-thymidylate synthase 0.1449 1 0.5

Activities

Activity type Activity value Assay description Source Reference
Caco-2 Papp (functional) = 0.000001 cm s-1 Permeability action of the compound in Caco-2 cells ChEMBL. 15357971
Caco-2 Papp (functional) = 0.000001 cm s-1 Permeability action of the compound in Caco-2 cells ChEMBL. 15357971
ED50 (functional) = 2.5 mg kg-1 Compound was tested for anti TNF-alpha activity using LPS mouse model at 10 mg/kg p.o. ChEMBL. 15357971
ED50 (functional) = 2.5 mg kg-1 Compound was tested for anti TNF-alpha activity using LPS mouse model at 10 mg/kg p.o. ChEMBL. 15357971
IC50 (binding) < 1 nM Inhibition of porcine Tumor necrosis factor- alpha converting enzyme (TACE, ADAM17) ChEMBL. 15357971
IC50 (binding) < 1 nM Inhibition of porcine Tumor necrosis factor- alpha converting enzyme (TACE, ADAM17) ChEMBL. 15357971
IC50 (binding) = 1 nM Inhibition of TACE ChEMBL. 19095454
IC50 (functional) = 180 nM Effect on TNF-Alpha release in LPS-stimulated human whole blood assay ChEMBL. 15357971
IC50 (functional) = 180 nM Effect on TNF-Alpha release in LPS-stimulated human whole blood assay ChEMBL. 15357971
Inhibition (functional) = 50 % Compound was tested for anti TNF-alpha activity using LPS mouse model at 10 mg/kg p.o. ChEMBL. 15357971
Inhibition (functional) = 50 % Compound was tested for anti TNF-alpha activity using LPS mouse model at 10 mg/kg p.o. ChEMBL. 15357971
Ki (binding) = 1708 nM Inhibition of Matrix metalloproteinase-13 (MMP-13) ChEMBL. 15357971
Ki (binding) = 1708 nM Inhibition of Matrix metalloproteinase-13 (MMP-13) ChEMBL. 15357971
Ki (binding) > 2100 nM Inhibition of Matrix metalloproteinase-9 (MMP-9) ChEMBL. 15357971
Ki (binding) > 2100 nM Inhibition of Matrix metalloproteinase-9 (MMP-9) ChEMBL. 15357971
Ki (binding) > 3300 nM inhibition of Matrix metalloproteinase-2 (MMP-2) ChEMBL. 15357971
Ki (binding) > 3300 nM inhibition of Matrix metalloproteinase-2 (MMP-2) ChEMBL. 15357971
Ki (binding) > 4900 nM Inhibition of Matrix metalloproteinase-1 (MMP-1) ChEMBL. 15357971
Ki (binding) > 4900 nM Inhibition of Matrix metalloproteinase-1 (MMP-1) ChEMBL. 15357971

Phenotypes

Whole-cell/tissue/organism interactions

We have no records of whole-cell/tissue assays done with this compound What does this mean?

Many chemical entities in TDR Targets come from high-throughput screenings with whole cells or tissue samples, and not all assayed compounds have been tested against a single a single target protein, probably because they get ruled out during screening process. Even if these compounds may have not been of interest in the original screening, they may come as interesting leads for other screening assays. Furthermore, we may be able to propose drug-target associations using chemical similarities and network patterns.

Annotated phenotypes:

We have no manually annotated phenotypes for this drug. What does this mean? / Care to help?
In TDR Targets, information about phenotypes that are caused by drugs, or by genetic manipulation of cells (e.g. gene knockouts or knockdowns) is manually curated from the literature. These descriptions help to describe the potential of the target for drug development. If no information is available for this gene or if the information is incomplete, this may mean that i) the papers containing this information either appeared after the curation effort for this organism was carried out or they were inadvertently missed by curators; or that ii) the curation effort for this organism has not yet started.
 
In any case, if you have information about papers containing relevant validation data for this target, please log in using your TDR Targets username and password and send them to us using the corresponding form in this page (only visible to registered users) or contact us.

External resources for this compound

Bibliographic References

2 literature references were collected for this gene.

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