Detailed information for compound 48409

Basic information

Technical information
  • TDR Targets ID: 48409
  • Name: 6-[3-[(2,4-diaminopyrimidin-5-yl)methyl]-4-me thoxyphenoxy]hexanoic acid
  • MW: 360.408 | Formula: C18H24N4O4
  • H donors: 3 H acceptors: 4 LogP: 1.94 Rotable bonds: 10
    Rule of 5 violations (Lipinski): 1
  • SMILES: COc1ccc(cc1Cc1cnc(nc1N)N)OCCCCCC(=O)O
  • InChi: 1S/C18H24N4O4/c1-25-15-7-6-14(26-8-4-2-3-5-16(23)24)10-12(15)9-13-11-21-18(20)22-17(13)19/h6-7,10-11H,2-5,8-9H2,1H3,(H,23,24)(H4,19,20,21,22)
  • InChiKey: IHHWPKHCZVGDIM-UHFFFAOYSA-N  


Substructure search Similarity search

Network

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Synonyms

  • 6-[3-[(2,4-diaminopyrimidin-5-yl)methyl]-4-methoxy-phenoxy]hexanoic acid
  • 6-[3-[(2,4-diamino-5-pyrimidinyl)methyl]-4-methoxyphenoxy]hexanoic acid
  • 6-[3-[[2,4-bis(azanyl)pyrimidin-5-yl]methyl]-4-methoxy-phenoxy]hexanoic acid
  • AIDS-114354
  • AIDS114354
  • Hexanoic acid, 6-[3-[(2,4-diamino-5-pyrimidinyl)methyl]-4-methoxyphenoxy]-

Targets

Known targets for this compound

Species Target name Source Bibliographic reference
Toxoplasma gondii bifunctional dihydrofolate reductase-thymidylate synthase Starlite/ChEMBL References
Rattus norvegicus Dihydrofolate reductase Starlite/ChEMBL References
Mycobacterium avium Dihydrofolate reductase Starlite/ChEMBL References
Escherichia coli Dihydrofolate reductase Starlite/ChEMBL References

Predicted pathogen targets for this compound

By orthology
Species Potential target Known druggable target/s Ortholog Group
Schistosoma mansoni bifunctional dihydrofolate reductase-thymidylate synthase Get druggable targets OG5_127385 All targets in OG5_127385
Schistosoma mansoni dihydrofolate reductase Get druggable targets OG5_128410 All targets in OG5_128410
Loa Loa (eye worm) dihydrofolate reductase 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
Echinococcus multilocularis 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
Schistosoma japonicum ko:K00560 thymidylate synthase [EC2.1.1.45], putative Get druggable targets OG5_127385 All targets in OG5_127385
Babesia bovis dihydrofolate reductase/thymidilate synthase 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 Thymidylate synthase capable of functional substitution for S. cerevisiae CDC21 (YOR074C) Get druggable targets OG5_127385 All targets in OG5_127385
Brugia malayi 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
Onchocerca volvulus Get druggable targets OG5_127385 All targets in OG5_127385
Schistosoma japonicum hypothetical protein 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
Leishmania donovani 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
Theileria parva dihydrofolate reductase-thymidylate synthase, putative 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
Plasmodium falciparum bifunctional dihydrofolate reductase-thymidylate synthase Get druggable targets OG5_127385 All targets in OG5_127385
Mycobacterium leprae PROBABLE THYMIDYLATE SYNTHASE THYA (TS) (TSASE) 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 tuberculosis Probable thymidylate synthase ThyA (ts) (TSASE) 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
Mycobacterium ulcerans thymidylate synthase 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
Echinococcus multilocularis dihydrofolate reductase 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
Plasmodium berghei bifunctional dihydrofolate reductase-thymidylate synthase, putative 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
Trypanosoma brucei dihydrofolate reductase-thymidylate synthase 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
Toxoplasma gondii bifunctional dihydrofolate reductase-thymidylate synthase 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
Cryptosporidium hominis chain A, crystal structure of Dhfr Get druggable targets OG5_127385 All targets in OG5_127385
Mycobacterium tuberculosis Dihydrofolate reductase DfrA (DHFR) (tetrahydrofolate dehydrogenase) Get druggable targets OG5_128410 All targets in OG5_128410
Leishmania mexicana dihydrofolate reductase-thymidylate synthase Get druggable targets OG5_127385 All targets in OG5_127385
Candida albicans dihydrofolate reductase Get druggable targets OG5_128410 All targets in OG5_128410
Echinococcus granulosus thymidylate synthase Get druggable targets OG5_127385 All targets in OG5_127385
Brugia malayi Dihydrofolate reductase Get druggable targets OG5_128410 All targets in OG5_128410
Plasmodium knowlesi bifunctional dihydrofolate reductase-thymidylate synthase, putative Get druggable targets OG5_127385 All targets in OG5_127385
Candida albicans hypothetical protein Get druggable targets OG5_128410 All targets in OG5_128410
Chlamydia trachomatis dihydrofolate reductase Get druggable targets OG5_128410 All targets in OG5_128410
Brugia malayi dihydrofolate reductase family protein Get druggable targets OG5_128410 All targets in OG5_128410
Trypanosoma brucei gambiense dihydrofolate reductase-thymidylate synthase 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
Mycobacterium tuberculosis Dihydrofolate reductase DfrA (DHFR) (tetrahydrofolate dehydrogenase) Dihydrofolate reductase   157 aa 160 aa 29.4 %
Dictyostelium discoideum dihydrofolate reductase Dihydrofolate reductase   157 aa 146 aa 27.4 %
Candida albicans dihydrofolate reductase Dihydrofolate reductase   157 aa 149 aa 29.5 %
Cryptosporidium parvum mannose-1-phosphate guanylyltransferase Dihydrofolate reductase   157 aa 139 aa 27.3 %
Plasmodium vivax hypothetical protein, conserved Dihydrofolate reductase   157 aa 127 aa 26.8 %
Plasmodium falciparum dihydrofolate synthase/folylpolyglutamate synthase Dihydrofolate reductase   157 aa 127 aa 19.7 %
Leishmania infantum dihydrofolate reductase-thymidylate synthase Dihydrofolate reductase   187 aa 172 aa 36.0 %
Cryptosporidium hominis chain A, crystal structure of Dhfr Dihydrofolate reductase   187 aa 182 aa 34.1 %
Plasmodium yoelii thymidylate synthase, putative Dihydrofolate reductase   187 aa 212 aa 27.8 %
Leishmania donovani serine carboxypeptidase (CBP1), putative Dihydrofolate reductase   157 aa 159 aa 23.3 %
Chlamydia trachomatis dihydrofolate reductase Dihydrofolate reductase   157 aa 133 aa 24.8 %
Leishmania braziliensis dihydrofolate reductase-thymidylate synthase Dihydrofolate reductase   187 aa 172 aa 34.3 %
Trypanosoma cruzi ATP- dependent RNA helicase, putative Dihydrofolate reductase   157 aa 140 aa 22.9 %
Leishmania major dihydrofolate reductase-thymidylate synthase Dihydrofolate reductase   187 aa 172 aa 36.0 %
Mycobacterium ulcerans dihydrofolate reductase DfrA Dihydrofolate reductase   157 aa 159 aa 28.3 %
Trypanosoma brucei gambiense dihydrofolate reductase-thymidylate synthase Dihydrofolate reductase   187 aa 210 aa 30.0 %
Babesia bovis dihydrofolate reductase/thymidilate synthase Dihydrofolate reductase   187 aa 191 aa 31.9 %
Cryptosporidium hominis GDP-mannose pyrophosphorylase (4N40) Dihydrofolate reductase   157 aa 139 aa 28.1 %
Onchocerca volvulus Putative dihydrofolate reductase Dihydrofolate reductase   181 aa 174 aa 31.6 %
Toxoplasma gondii bifunctional dihydrofolate reductase-thymidylate synthase Dihydrofolate reductase   187 aa 186 aa 37.1 %
Leishmania major serine carboxypeptidase (CBP1), putative,serine peptidase, Clan SC, Family S10 Dihydrofolate reductase   157 aa 159 aa 21.4 %
Leishmania donovani dihydrofolate reductase-thymidylate synthase Dihydrofolate reductase   187 aa 172 aa 36.0 %
Candida albicans dihydrofolate reductase Dihydrofolate reductase   157 aa 149 aa 29.5 %
Trypanosoma cruzi dihydrofolate reductase-thymidylate synthase Dihydrofolate reductase   157 aa 137 aa 29.2 %
Plasmodium knowlesi bifunctional dihydrofolate reductase-thymidylate synthase, putative Dihydrofolate reductase   187 aa 209 aa 29.2 %
Mycobacterium leprae DIHYDROFOLATE REDUCTASE DFRA (DHFR) (TETRAHYDROFOLATE DEHYDROGENASE) Dihydrofolate reductase   157 aa 158 aa 29.1 %
Candida albicans hypothetical protein Dihydrofolate reductase   157 aa 149 aa 29.5 %
Schistosoma mansoni dihydrofolate reductase Dihydrofolate reductase   157 aa 147 aa 28.6 %
Leishmania infantum serine carboxypeptidase (CBP1), putative,serine peptidase, Clan SC, Family S10 Dihydrofolate reductase   157 aa 159 aa 23.3 %
Theileria parva dihydrofolate reductase-thymidylate synthase, putative Dihydrofolate reductase   187 aa 193 aa 32.1 %
Trypanosoma brucei dihydrofolate reductase-thymidylate synthase Dihydrofolate reductase   187 aa 210 aa 30.0 %
Cryptosporidium parvum dihydrofolate reductase-thymidylate synthase Dihydrofolate reductase   187 aa 182 aa 33.5 %
Neospora caninum Bifunctional dihydrofolate reductase-thymidylate synthase, related Dihydrofolate reductase   187 aa 187 aa 35.8 %
Plasmodium berghei bifunctional dihydrofolate reductase-thymidylate synthase, putative Dihydrofolate reductase   187 aa 211 aa 28.4 %
Plasmodium falciparum bifunctional dihydrofolate reductase-thymidylate synthase Dihydrofolate reductase   187 aa 202 aa 29.2 %
Onchocerca volvulus Germline survival defective-1 homolog Dihydrofolate reductase   157 aa 165 aa 24.8 %
Plasmodium vivax bifunctional dihydrofolate reductase-thymidylate synthase, putative Dihydrofolate reductase   187 aa 209 aa 29.2 %
Plasmodium yoelii hypothetical protein Dihydrofolate reductase   157 aa 132 aa 24.2 %
Leishmania mexicana dihydrofolate reductase-thymidylate synthase Dihydrofolate reductase   187 aa 172 aa 33.7 %
Obtained from network model

Ranking Plot

Putative Targets List

Species Potential target Raw Global Species
Schistosoma mansoni dihydrofolate reductase 0.0547 1 1
Chlamydia trachomatis dihydrofolate reductase 0.0547 1 0.5
Mycobacterium tuberculosis Dihydrofolate reductase DfrA (DHFR) (tetrahydrofolate dehydrogenase) 0.0547 1 1
Echinococcus multilocularis dihydrofolate reductase 0.0547 1 1
Trypanosoma brucei dihydrofolate reductase-thymidylate synthase 0.0421 0.6968 0.5
Trypanosoma cruzi dihydrofolate reductase-thymidylate synthase 0.0421 0.6968 0.5
Onchocerca volvulus 0.013 0 0.5
Echinococcus granulosus dihydrofolate reductase 0.0547 1 1
Leishmania major dihydrofolate reductase-thymidylate synthase 0.0421 0.6968 0.5
Mycobacterium leprae DIHYDROFOLATE REDUCTASE DFRA (DHFR) (TETRAHYDROFOLATE DEHYDROGENASE) 0.0547 1 1
Plasmodium falciparum bifunctional dihydrofolate reductase-thymidylate synthase 0.0421 0.6968 0.5
Loa Loa (eye worm) dihydrofolate reductase 0.0547 1 1
Toxoplasma gondii bifunctional dihydrofolate reductase-thymidylate synthase 0.0421 0.6968 0.5
Brugia malayi Dihydrofolate reductase 0.0547 1 1
Mycobacterium ulcerans dihydrofolate reductase DfrA 0.0547 1 1
Plasmodium vivax bifunctional dihydrofolate reductase-thymidylate synthase, putative 0.0421 0.6968 0.5

Activities

Activity type Activity value Assay description Source Reference
Concentration (functional) = 32 ug ml-1 Concentration of compound required against Mycobacterium avium; Range is 4-32 ChEMBL. 14998335
IC50 (binding) = 0.15 uM Inhibition of partially purified dihydrofolate reductase (DHFR) from Mycobacterium avium (Ma) ChEMBL. 11754594
IC50 (binding) = 0.15 uM Inhibition of partially purified dihydrofolate reductase (DHFR) from Mycobacterium avium (Ma) ChEMBL. 11754594
IC50 (binding) = 0.48 uM Inhibition of partially purified dihydrofolate reductase (DHFR) from Toxoplasma gondii (Tg) ChEMBL. 11754594
IC50 (binding) = 0.48 uM Inhibition of partially purified dihydrofolate reductase (DHFR) from Toxoplasma gondii (Tg) ChEMBL. 11754594
IC50 (binding) = 0.8 uM In vitro inhibition of Pneumocystis carinii (Pc) dihydrofolate reductase. ChEMBL. 11754594
IC50 (binding) = 0.8 uM In vitro inhibition of Pneumocystis carinii (Pc) dihydrofolate reductase. ChEMBL. 11754594
IC50 (binding) = 17 uM Inhibition of partially purified dihydrofolate reductase (DHFR) from rat liver ChEMBL. 11754594
IC50 (binding) = 17 uM Inhibition of partially purified dihydrofolate reductase (DHFR) from rat liver ChEMBL. 11754594
MIC (functional) = 8 ug ml-1 Minimum inhibitory concentration required against Mycobacterium avium isolate from patient number MAC101 ChEMBL. 14998335
MIC (functional) = 8 ug ml-1 Minimum inhibitory concentration required against Mycobacterium avium isolate from patient number MAC109 ChEMBL. 14998335
MIC (functional) = 8 ug ml-1 Minimum inhibitory concentration required against Mycobacterium avium isolate from patient number MAC16 ChEMBL. 14998335
MIC (functional) = 16 ug ml-1 Minimum inhibitory concentration required against Mycobacterium avium isolate from patient number MAC100 ChEMBL. 14998335
MIC (functional) = 32 ug ml-1 Minimum inhibitory concentration required against Mycobacterium avium isolate from patient number MAC108 ChEMBL. 14998335
MIC50 (functional) = 4 ug ml-1 Minimum inhibitory concentration required for 50 percent inhibition of Mycobacterium avium isolate ChEMBL. 14998335
MIC90 (functional) = 32 ug ml-1 Minimum inhibitory concentration required for 90 percent inhibition of Mycobacterium avium isolate ChEMBL. 14998335
SI (binding) = 21 Selective index against dihydrofolate reductase of Rat liver and dihydrofolate reductase of P. carinii ChEMBL. 11754594
SI (binding) = 35 Selective index against dihydrofolate reductase of Rat liver and T. gondii ChEMBL. 11754594
SI (binding) = 110 Selective index for rat liver and M. avium dihydrofolate reductase ChEMBL. 11754594
SI (binding) = 21 Selective index against dihydrofolate reductase of Rat liver and dihydrofolate reductase of P. carinii ChEMBL. 11754594
SI (binding) = 35 Selective index against dihydrofolate reductase of Rat liver and T. gondii ChEMBL. 11754594
SI (binding) = 110 Selective index for rat liver and M. avium dihydrofolate reductase ChEMBL. 11754594

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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