Detailed information for compound 84710

Basic information

Technical information
  • TDR Targets ID: 84710
  • Name: 5-[(3,5-dimethoxy-4-methylsulfanylphenyl)meth yl]pyrimidine-2,4-diamine
  • MW: 306.383 | Formula: C14H18N4O2S
  • H donors: 2 H acceptors: 2 LogP: 1.88 Rotable bonds: 5
    Rule of 5 violations (Lipinski): 1
  • SMILES: COc1cc(Cc2cnc(nc2N)N)cc(c1SC)OC
  • InChi: 1S/C14H18N4O2S/c1-19-10-5-8(6-11(20-2)12(10)21-3)4-9-7-17-14(16)18-13(9)15/h5-7H,4H2,1-3H3,(H4,15,16,17,18)
  • InChiKey: HRZQMMXCASMDBP-UHFFFAOYSA-N  


Substructure search Similarity search

Network

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Synonyms

  • 5-[(3,5-dimethoxy-4-methylsulfanyl-phenyl)methyl]pyrimidine-2,4-diamine
  • 5-[[3,5-dimethoxy-4-(methylthio)phenyl]methyl]pyrimidine-2,4-diamine
  • [2-amino-5-[3,5-dimethoxy-4-(methylthio)benzyl]pyrimidin-4-yl]amine
  • metioprim
  • 68902-57-8
  • 2,4-Diamino-5-(3,5-dimethoxy-4-methylthiobenzyl)pyrimidine
  • 2,4-Diamino-5-(3,5-dimethoxy-4-(methylthio)benzyl)pyrimidine
  • 2,4-Pyrimidinediamine, 5-((3,5-dimethoxy-4-(methylthio)phenyl)methyl)-
  • 5-((3,5-Dimethoxy-4-(methylthio)phenyl)methyl)-2,4-pyrimidinediamine
  • He 909
  • Methioprim (bacteriostat)
  • Metioprim [USAN:BAN:INN]
  • Metioprima [INN-Spanish]
  • Metioprime [INN-French]
  • Metioprimum [INN-Latin]
  • Ro 12-6995
  • Ro 126995
  • AIDS093628
  • AIDS-093628
  • D05005
  • Metioprim (USAN)

Targets

Known targets for this compound

Species Target name Source Bibliographic reference
Lactobacillus casei Dihydrofolate reductase Starlite/ChEMBL References
Toxoplasma gondii bifunctional dihydrofolate reductase-thymidylate synthase Curated by TDR Targets References
Salmonella enterica subsp. enterica serovar Typhi Dihydrofolate reductase Starlite/ChEMBL References

Predicted pathogen targets for this compound

By orthology
Species Potential target Known druggable target/s Ortholog Group
Plasmodium berghei bifunctional dihydrofolate reductase-thymidylate synthase, putative Get druggable targets OG5_127385 All targets in OG5_127385
Schistosoma japonicum ko:K00287 dihydrofolate reductase [EC1.5.1.3], putative Get druggable targets OG5_128410 All targets in OG5_128410
Candida albicans hypothetical protein Get druggable targets OG5_128410 All targets in OG5_128410
Brugia malayi thymidylate synthase Get druggable targets OG5_127385 All targets in OG5_127385
Cryptosporidium parvum dihydrofolate reductase-thymidylate synthase Get druggable targets OG5_127385 All targets in OG5_127385
Leishmania infantum dihydrofolate reductase-thymidylate synthase Get druggable targets OG5_127385 All targets in OG5_127385
Cryptosporidium hominis chain A, crystal structure of Dhfr Get druggable targets OG5_127385 All targets in OG5_127385
Mycobacterium ulcerans dihydrofolate reductase DfrA Get druggable targets OG5_128410 All targets in OG5_128410
Mycobacterium leprae PROBABLE THYMIDYLATE SYNTHASE THYA (TS) (TSASE) Get druggable targets OG5_127385 All targets in OG5_127385
Loa Loa (eye worm) thymidylate synthase Get druggable targets OG5_127385 All targets in OG5_127385
Brugia malayi dihydrofolate reductase family protein Get druggable targets OG5_128410 All targets in OG5_128410
Plasmodium vivax bifunctional dihydrofolate reductase-thymidylate synthase, putative Get druggable targets OG5_127385 All targets in OG5_127385
Trypanosoma cruzi dihydrofolate reductase-thymidylate synthase Get druggable targets OG5_127385 All targets in OG5_127385
Trypanosoma brucei gambiense dihydrofolate reductase-thymidylate synthase Get druggable targets OG5_127385 All targets in OG5_127385
Schistosoma mansoni bifunctional dihydrofolate reductase-thymidylate synthase Get druggable targets OG5_127385 All targets in OG5_127385
Candida albicans Thymidylate synthase capable of functional substitution for S. cerevisiae CDC21 (YOR074C) Get druggable targets OG5_127385 All targets in OG5_127385
Echinococcus multilocularis thymidylate synthase Get druggable targets OG5_127385 All targets in OG5_127385
Plasmodium falciparum bifunctional dihydrofolate reductase-thymidylate synthase Get druggable targets OG5_127385 All targets in OG5_127385
Leishmania mexicana dihydrofolate reductase-thymidylate synthase Get druggable targets OG5_127385 All targets in OG5_127385
Leishmania major dihydrofolate reductase-thymidylate synthase Get druggable targets OG5_127385 All targets in OG5_127385
Mycobacterium leprae DIHYDROFOLATE REDUCTASE DFRA (DHFR) (TETRAHYDROFOLATE DEHYDROGENASE) Get druggable targets OG5_128410 All targets in OG5_128410
Leishmania braziliensis dihydrofolate reductase-thymidylate synthase Get druggable targets OG5_127385 All targets in OG5_127385
Trypanosoma brucei dihydrofolate reductase-thymidylate synthase Get druggable targets OG5_127385 All targets in OG5_127385
Echinococcus multilocularis dihydrofolate reductase Get druggable targets OG5_128410 All targets in OG5_128410
Brugia malayi Dihydrofolate reductase Get druggable targets OG5_128410 All targets in OG5_128410
Schistosoma japonicum ko:K00560 thymidylate synthase [EC2.1.1.45], putative Get druggable targets OG5_127385 All targets in OG5_127385
Schistosoma mansoni dihydrofolate reductase Get druggable targets OG5_128410 All targets in OG5_128410
Mycobacterium tuberculosis Dihydrofolate reductase DfrA (DHFR) (tetrahydrofolate dehydrogenase) Get druggable targets OG5_128410 All targets in OG5_128410
Candida albicans Thymidylate synthase capable of functional substitution for S. cerevisiae CDC21 (YOR074C) Get druggable targets OG5_127385 All targets in OG5_127385
Loa Loa (eye worm) dihydrofolate reductase Get druggable targets OG5_128410 All targets in OG5_128410
Schistosoma japonicum hypothetical protein Get druggable targets OG5_127385 All targets in OG5_127385
Neospora caninum Bifunctional dihydrofolate reductase-thymidylate synthase, related Get druggable targets OG5_127385 All targets in OG5_127385
Candida albicans dihydrofolate reductase Get druggable targets OG5_128410 All targets in OG5_128410
Babesia bovis dihydrofolate reductase/thymidilate synthase Get druggable targets OG5_127385 All targets in OG5_127385
Chlamydia trachomatis dihydrofolate reductase Get druggable targets OG5_128410 All targets in OG5_128410
Onchocerca volvulus Get druggable targets OG5_127385 All targets in OG5_127385
Leishmania donovani dihydrofolate reductase-thymidylate synthase Get druggable targets OG5_127385 All targets in OG5_127385
Echinococcus granulosus dihydrofolate reductase Get druggable targets OG5_128410 All targets in OG5_128410
Theileria parva dihydrofolate reductase-thymidylate synthase, putative Get druggable targets OG5_127385 All targets in OG5_127385
Mycobacterium tuberculosis Probable thymidylate synthase ThyA (ts) (TSASE) Get druggable targets OG5_127385 All targets in OG5_127385
Candida albicans dihydrofolate reductase Get druggable targets OG5_128410 All targets in OG5_128410
Toxoplasma gondii bifunctional dihydrofolate reductase-thymidylate synthase Get druggable targets OG5_127385 All targets in OG5_127385
Echinococcus granulosus thymidylate synthase Get druggable targets OG5_127385 All targets in OG5_127385
Mycobacterium ulcerans thymidylate synthase Get druggable targets OG5_127385 All targets in OG5_127385
Plasmodium yoelii thymidylate synthase, putative Get druggable targets OG5_127385 All targets in OG5_127385
Plasmodium knowlesi bifunctional dihydrofolate reductase-thymidylate synthase, putative Get druggable targets OG5_127385 All targets in OG5_127385
By sequence similarity to non orthologous known druggable targets
Species Potential target Known druggable target Length Alignment span Identity
Leishmania donovani dihydrofolate reductase-thymidylate synthase Dihydrofolate reductase   159 aa 173 aa 28.9 %
Onchocerca volvulus Putative dihydrofolate reductase Dihydrofolate reductase   163 aa 173 aa 27.2 %
Plasmodium yoelii thymidylate synthase, putative Dihydrofolate reductase   163 aa 139 aa 21.6 %
Cryptosporidium hominis chain A, crystal structure of Dhfr Dihydrofolate reductase   159 aa 173 aa 31.8 %
Trypanosoma cruzi dihydrofolate reductase-thymidylate synthase Dihydrofolate reductase   159 aa 160 aa 30.6 %
Leishmania infantum dihydrofolate reductase-thymidylate synthase Dihydrofolate reductase   159 aa 173 aa 28.9 %
Leishmania major dihydrofolate reductase-thymidylate synthase Dihydrofolate reductase   159 aa 173 aa 28.9 %
Cryptosporidium parvum dihydrofolate reductase-thymidylate synthase Dihydrofolate reductase   159 aa 173 aa 30.6 %
Plasmodium vivax bifunctional dihydrofolate reductase-thymidylate synthase, putative Dihydrofolate reductase   159 aa 131 aa 29.0 %
Trypanosoma brucei dihydrofolate reductase-thymidylate synthase Dihydrofolate reductase   159 aa 130 aa 30.8 %
Toxoplasma gondii bifunctional dihydrofolate reductase-thymidylate synthase Dihydrofolate reductase   163 aa 138 aa 29.7 %
Neospora caninum Bifunctional dihydrofolate reductase-thymidylate synthase, related Dihydrofolate reductase   159 aa 203 aa 28.6 %
Babesia bovis dihydrofolate reductase/thymidilate synthase Dihydrofolate reductase   163 aa 133 aa 27.1 %
Leishmania braziliensis dihydrofolate reductase-thymidylate synthase Dihydrofolate reductase   159 aa 173 aa 28.9 %
Theileria parva dihydrofolate reductase-thymidylate synthase, putative Dihydrofolate reductase   159 aa 195 aa 22.6 %
Trypanosoma brucei gambiense dihydrofolate reductase-thymidylate synthase Dihydrofolate reductase   159 aa 130 aa 30.8 %
Onchocerca volvulus Germline survival defective-1 homolog Dihydrofolate reductase   159 aa 166 aa 26.5 %
Leishmania mexicana dihydrofolate reductase-thymidylate synthase Dihydrofolate reductase   159 aa 173 aa 28.9 %
Plasmodium berghei bifunctional dihydrofolate reductase-thymidylate synthase, putative Dihydrofolate reductase   159 aa 140 aa 31.4 %
Obtained from network model

Ranking Plot

Putative Targets List

Species Potential target Raw Global Species
Trypanosoma brucei dihydrofolate reductase-thymidylate synthase 0.0341 0.6943 0.5
Schistosoma mansoni peptidase Clp (S14 family) 0.0088 0.0832 0.0832
Loa Loa (eye worm) pigment dispersing factor receptor c 0.017 0.28 0.28
Toxoplasma gondii bifunctional dihydrofolate reductase-thymidylate synthase 0.0341 0.6943 1
Trichomonas vaginalis conserved hypothetical protein 0.0062 0.0194 0.5
Plasmodium falciparum bifunctional dihydrofolate reductase-thymidylate synthase 0.0341 0.6943 1
Mycobacterium leprae PROBABLE THYMIDYLATE SYNTHASE THYA (TS) (TSASE) 0.013 0.1836 0.1754
Mycobacterium leprae DIHYDROFOLATE REDUCTASE DFRA (DHFR) (TETRAHYDROFOLATE DEHYDROGENASE) 0.0468 1 1
Loa Loa (eye worm) thymidylate synthase 0.013 0.1836 0.1836
Treponema pallidum ATP-dependent Clp protease proteolytic subunit 0.0088 0.0832 0.5
Schistosoma mansoni hypothetical protein 0.0116 0.1504 0.1504
Echinococcus granulosus tumor protein p63 0.0381 0.79 0.79
Schistosoma mansoni dihydrofolate reductase 0.0468 1 1
Brugia malayi Corticotropin releasing factor receptor 2 precursor, putative 0.017 0.28 0.28
Chlamydia trachomatis dihydrofolate reductase 0.0468 1 1
Echinococcus multilocularis thymidylate synthase 0.013 0.1836 0.1836
Loa Loa (eye worm) hypothetical protein 0.017 0.28 0.28
Plasmodium vivax bifunctional dihydrofolate reductase-thymidylate synthase, putative 0.0341 0.6943 1
Echinococcus multilocularis geminin 0.0387 0.8044 0.8044
Echinococcus granulosus dihydrofolate reductase 0.0468 1 1
Schistosoma mansoni hypothetical protein 0.0387 0.8044 0.8044
Loa Loa (eye worm) dihydrofolate reductase 0.0468 1 1
Echinococcus multilocularis peptidase Clp (S14 family) 0.0058 0.0099 0.0099
Wolbachia endosymbiont of Brugia malayi ATP-dependent Clp protease proteolytic subunit 0.0088 0.0832 0.5
Onchocerca volvulus 0.013 0.1836 1
Mycobacterium tuberculosis Hypothetical protein 0.0062 0.0194 0.0096
Leishmania major dihydrofolate reductase-thymidylate synthase 0.0341 0.6943 0.5
Echinococcus granulosus peptidase Clp S14 family 0.0058 0.0099 0.0099
Mycobacterium tuberculosis Dihydrofolate reductase DfrA (DHFR) (tetrahydrofolate dehydrogenase) 0.0468 1 1
Mycobacterium leprae PROBABLE ATP-DEPENDENT CLP PROTEASE PROTEOLYTIC SUBUNIT 2 CLPP2 (ENDOPEPTIDASE CLP 2) 0.0088 0.0832 0.0741
Echinococcus granulosus ATP dependent Clp protease proteolytic subunit 0.0088 0.0832 0.0832
Brugia malayi hypothetical protein 0.0062 0.0194 0.0194
Brugia malayi latrophilin 2 splice variant baaae 0.0116 0.1504 0.1504
Mycobacterium tuberculosis Probable thymidylate synthase ThyA (ts) (TSASE) 0.013 0.1836 0.1754
Schistosoma mansoni hypothetical protein 0.0387 0.8044 0.8044
Loa Loa (eye worm) hypothetical protein 0.0088 0.0832 0.0832
Mycobacterium ulcerans thymidylate synthase 0.013 0.1836 0.1094
Mycobacterium ulcerans dihydrofolate reductase DfrA 0.0468 1 1
Echinococcus multilocularis ATP dependent Clp protease proteolytic subunit 0.0088 0.0832 0.0832
Loa Loa (eye worm) hypothetical protein 0.0056 0.005 0.005
Schistosoma mansoni bifunctional dihydrofolate reductase-thymidylate synthase 0.013 0.1836 0.1836
Loa Loa (eye worm) hypothetical protein 0.0116 0.1504 0.1504
Brugia malayi Dihydrofolate reductase 0.0468 1 1
Echinococcus multilocularis dihydrofolate reductase 0.0468 1 1
Echinococcus granulosus thymidylate synthase 0.013 0.1836 0.1836
Brugia malayi Probable ClpP-like protease 0.0088 0.0832 0.0832
Brugia malayi Calcitonin receptor-like protein seb-1 0.017 0.28 0.28
Schistosoma mansoni cellular tumor antigen P53 0.0056 0.005 0.005
Echinococcus multilocularis tumor protein p63 0.0381 0.79 0.79
Trypanosoma cruzi dihydrofolate reductase-thymidylate synthase 0.0341 0.6943 1
Brugia malayi thymidylate synthase 0.013 0.1836 0.1836
Echinococcus granulosus geminin 0.0387 0.8044 0.8044

Activities

Activity type Activity value Assay description Source Reference
Activity (binding) = 8.07 Inhibitory activity against dihydrofolate reductase ChEMBL. 11495588
Activity (binding) = 8.07 Activity against dihydrofolate reductase of Escherichia coli strain MB 1428 ChEMBL. 1507206
Ki (binding) = 4.29 Inhibitory activity against chicken liver dihydrofolate reductase ChEMBL. 2502631
Ki (binding) = 7.25 Inhibitory activity against Lactobacillus casei dihydrofolate reductase ChEMBL. 2502631
Ki (binding) = 8.07 Inhibitory activity against E. coli dihydrofolate reductase ChEMBL. 1899453
Log (binding) = 8.07 1/Ki Inhibitory activity against E. coli dihydrofolate reductase ChEMBL. 1899453
Log 1/C (binding) = 4.29 Inhibition of chicken liver dihydrofolate reductase ChEMBL. 3701780
Log 1/C (functional) = 5.66 Inhibition of growth of methotrexate-resistant (MB1428) strain of Escherichia coli cells. ChEMBL. 3934385
Log 1/C (functional) = 6.97 Inhibition of growth of methotrexate-sensitive (MB1417) strain of Escherichia coli cells. ChEMBL. 3934385
Log 1/C (binding) = 4.29 Inhibition of chicken liver dihydrofolate reductase ChEMBL. 3701780
Log 1/C (functional) = 5.66 Inhibition of growth of methotrexate-resistant (MB1428) strain of Escherichia coli cells. ChEMBL. 3934385
Log 1/C (functional) = 6.97 Inhibition of growth of methotrexate-sensitive (MB1417) strain of Escherichia coli cells. ChEMBL. 3934385
Log 1/Ki (binding) = 4.29 Inhibitory activity against chicken liver dihydrofolate reductase ChEMBL. 2502631
Log 1/Ki (binding) = 7.25 Inhibitory activity against Lactobacillus casei dihydrofolate reductase ChEMBL. 2502631
logD (ADMET) = 1.54 Partition coefficient (logD) (0.01 N NaOH) ChEMBL. 2502631
logD (ADMET) = 1.6 Partition coefficient (logD) (aqueous phase 0.1 N HCl) ChEMBL. 3701780

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

7 literature references were collected for this gene.

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