Detailed information for compound 77820

Basic information

Technical information
  • TDR Targets ID: 77820
  • Name: 6-[5-[(2,4-diaminopyrimidin-5-yl)methyl]-2,3- dimethoxyphenyl]hex-5-ynoic acid
  • MW: 370.402 | Formula: C19H22N4O4
  • H donors: 3 H acceptors: 4 LogP: 1.88 Rotable bonds: 7
    Rule of 5 violations (Lipinski): 1
  • SMILES: COc1c(C#CCCCC(=O)O)cc(cc1OC)Cc1cnc(nc1N)N
  • InChi: 1S/C19H22N4O4/c1-26-15-10-12(9-14-11-22-19(21)23-18(14)20)8-13(17(15)27-2)6-4-3-5-7-16(24)25/h8,10-11H,3,5,7,9H2,1-2H3,(H,24,25)(H4,20,21,22,23)
  • InChiKey: JAGSWKLZBKKKJP-UHFFFAOYSA-N  

Network

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Synonyms

  • 6-[5-[(2,4-diaminopyrimidin-5-yl)methyl]-2,3-dimethoxy-phenyl]hex-5-ynoic acid
  • 6-[5-[(2,4-diamino-5-pyrimidinyl)methyl]-2,3-dimethoxyphenyl]-5-hexynoic acid
  • 6-[5-[[2,4-bis(azanyl)pyrimidin-5-yl]methyl]-2,3-dimethoxy-phenyl]hex-5-ynoic acid
  • 6-[5-[(2,4-diamino-5-pyrimidinyl)methyl]-2,3-dimethoxyphenyl]hex-5-ynoic acid
  • 2,4-Diamino-5-[3',4'-dimethoxy-5'-(5-carboxy-1-pentynyl)benzyl]pyrimidine
  • AIDS-208402
  • AIDS208402

Targets

Known targets for this compound

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

Predicted pathogen targets for this compound

By orthology
Species Potential target Known druggable target/s Ortholog Group
Schistosoma japonicum ko:K00287 dihydrofolate reductase [EC1.5.1.3], putative Get druggable targets OG5_128410 All targets in OG5_128410
Loa Loa (eye worm) thymidylate synthase Get druggable targets OG5_127385 All targets in OG5_127385
Brugia malayi 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
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 dihydrofolate reductase family protein Get druggable targets OG5_128410 All targets in OG5_128410
Leishmania donovani dihydrofolate reductase-thymidylate synthase 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
Candida albicans dihydrofolate reductase 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
Schistosoma japonicum hypothetical protein Get druggable targets OG5_127385 All targets in OG5_127385
Chlamydia trachomatis 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
Trypanosoma brucei gambiense 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
Cryptosporidium hominis chain A, crystal structure of Dhfr 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
Schistosoma japonicum ko:K00560 thymidylate synthase [EC2.1.1.45], putative 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 falciparum bifunctional 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 multilocularis dihydrofolate reductase 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
Theileria parva dihydrofolate reductase-thymidylate synthase, putative Get druggable targets OG5_127385 All targets in OG5_127385
Echinococcus granulosus dihydrofolate reductase Get druggable targets OG5_128410 All targets in OG5_128410
Cryptosporidium parvum 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
Mycobacterium ulcerans dihydrofolate reductase DfrA 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
Echinococcus multilocularis thymidylate synthase 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
Candida albicans Thymidylate synthase capable of functional substitution for S. cerevisiae CDC21 (YOR074C) 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
Schistosoma mansoni bifunctional 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
Leishmania mexicana 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 tuberculosis Probable thymidylate synthase ThyA (ts) (TSASE) Get druggable targets OG5_127385 All targets in OG5_127385
Onchocerca volvulus 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
Brugia malayi Dihydrofolate reductase Get druggable targets OG5_128410 All targets in OG5_128410
Neospora caninum Bifunctional dihydrofolate reductase-thymidylate synthase, related Get druggable targets OG5_127385 All targets in OG5_127385
Schistosoma mansoni dihydrofolate reductase Get druggable targets OG5_128410 All targets in OG5_128410
Candida albicans hypothetical 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
Loa Loa (eye worm) dihydrofolate reductase Get druggable targets OG5_128410 All targets in OG5_128410

By sequence similarity to non orthologous known druggable targets
Species Potential target Known druggable target Length Alignment span Identity
Trypanosoma brucei gambiense dihydrofolate reductase-thymidylate synthase Dihydrofolate reductase   187 aa 210 aa 30.0 %
Plasmodium falciparum bifunctional dihydrofolate reductase-thymidylate synthase Dihydrofolate reductase   187 aa 202 aa 29.2 %
Neospora caninum Bifunctional dihydrofolate reductase-thymidylate synthase, related Dihydrofolate reductase   187 aa 187 aa 35.8 %
Leishmania infantum dihydrofolate reductase-thymidylate synthase Dihydrofolate reductase   187 aa 172 aa 36.0 %
Plasmodium knowlesi bifunctional dihydrofolate reductase-thymidylate synthase, putative Dihydrofolate reductase   187 aa 209 aa 29.2 %
Trypanosoma brucei dihydrofolate reductase-thymidylate synthase Dihydrofolate reductase   187 aa 210 aa 30.0 %
Plasmodium berghei bifunctional dihydrofolate reductase-thymidylate synthase, putative Dihydrofolate reductase   187 aa 211 aa 28.4 %
Onchocerca volvulus Putative dihydrofolate reductase Dihydrofolate reductase   181 aa 174 aa 31.6 %
Leishmania mexicana dihydrofolate reductase-thymidylate synthase Dihydrofolate reductase   187 aa 172 aa 33.7 %
Trypanosoma cruzi dihydrofolate reductase-thymidylate synthase Dihydrofolate reductase   206 aa 193 aa 29.5 %
Plasmodium yoelii thymidylate synthase, putative Dihydrofolate reductase   187 aa 212 aa 27.8 %
Theileria parva dihydrofolate reductase-thymidylate synthase, putative Dihydrofolate reductase   187 aa 193 aa 32.1 %
Cryptosporidium hominis chain A, crystal structure of Dhfr Dihydrofolate reductase   187 aa 182 aa 34.1 %
Cryptosporidium parvum dihydrofolate reductase-thymidylate synthase Dihydrofolate reductase   187 aa 182 aa 33.5 %
Plasmodium vivax bifunctional dihydrofolate reductase-thymidylate synthase, putative Dihydrofolate reductase   187 aa 209 aa 29.2 %
Toxoplasma gondii bifunctional dihydrofolate reductase-thymidylate synthase Dihydrofolate reductase   187 aa 186 aa 37.1 %
Leishmania donovani dihydrofolate reductase-thymidylate synthase Dihydrofolate reductase   187 aa 172 aa 36.0 %
Leishmania major dihydrofolate reductase-thymidylate synthase Dihydrofolate reductase   187 aa 172 aa 36.0 %
Leishmania braziliensis dihydrofolate reductase-thymidylate synthase Dihydrofolate reductase   187 aa 172 aa 34.3 %
Babesia bovis dihydrofolate reductase/thymidilate synthase Dihydrofolate reductase   187 aa 191 aa 31.9 %

Obtained from network model

Ranking Plot


Putative Targets List


Species Potential target Raw Global Species
Schistosoma mansoni dihydrofolate reductase 0.0676 1 1
Echinococcus multilocularis dihydrofolate reductase 0.0676 1 1
Brugia malayi Dihydrofolate reductase 0.0676 1 1
Loa Loa (eye worm) dihydrofolate reductase 0.0676 1 1
Mycobacterium leprae DIHYDROFOLATE REDUCTASE DFRA (DHFR) (TETRAHYDROFOLATE DEHYDROGENASE) 0.0676 1 1
Chlamydia trachomatis dihydrofolate reductase 0.0676 1 0.5
Onchocerca volvulus 0.013 0 0.5
Trypanosoma cruzi dihydrofolate reductase-thymidylate synthase 0.0421 0.5331 0.5
Toxoplasma gondii bifunctional dihydrofolate reductase-thymidylate synthase 0.0421 0.5331 0.5
Mycobacterium ulcerans dihydrofolate reductase DfrA 0.0676 1 1
Echinococcus granulosus dihydrofolate reductase 0.0676 1 1
Plasmodium vivax bifunctional dihydrofolate reductase-thymidylate synthase, putative 0.0421 0.5331 0.5
Mycobacterium tuberculosis Dihydrofolate reductase DfrA (DHFR) (tetrahydrofolate dehydrogenase) 0.0676 1 1
Trypanosoma brucei dihydrofolate reductase-thymidylate synthase 0.0421 0.5331 0.5
Plasmodium falciparum bifunctional dihydrofolate reductase-thymidylate synthase 0.0421 0.5331 0.5
Leishmania major dihydrofolate reductase-thymidylate synthase 0.0421 0.5331 0.5

Activities

Activity type Activity value Assay description Source Reference
IC50 (binding) = 1 nM Inhibitory concentration against Pneumocystis carinii dihydrofolate reductase ChEMBL. 15026078
IC50 (binding) = 1 nM Inhibitory concentration against Pneumocystis carinii DHFR ChEMBL. 15974594
IC50 (binding) = 1 nM Inhibitory concentration against Pneumocystis carinii dihydrofolate reductase ChEMBL. 15026078
IC50 (binding) = 1 nM Inhibitory concentration against Pneumocystis carinii DHFR ChEMBL. 15974594
IC50 (binding) = 2.4 nM Inhibitory concentration against Mycobacterium avium dihydrofolate reductase ChEMBL. 15026078
IC50 (binding) = 2.4 nM Inhibitory concentration against Mycobacterium avium DHFR ChEMBL. 15974594
IC50 (binding) = 2.4 nM Inhibitory concentration against Mycobacterium avium dihydrofolate reductase ChEMBL. 15026078
IC50 (binding) = 2.4 nM Inhibitory concentration against Mycobacterium avium DHFR ChEMBL. 15974594
IC50 (binding) = 34 nM Inhibitory concentration against Toxoplasma gondii dihydrofolate reductase ChEMBL. 15026078
IC50 (binding) = 34 nM Inhibitory concentration against Toxoplasma gondii DHFR ChEMBL. 15974594
IC50 (binding) = 34 nM Inhibitory concentration against Toxoplasma gondii dihydrofolate reductase ChEMBL. 15026078
IC50 (binding) = 34 nM Inhibitory concentration against Toxoplasma gondii DHFR ChEMBL. 15974594
IC50 (binding) = 5000 nM Inhibitory activity of the compound against rat dihydrofolate reductase ChEMBL. 15026078
IC50 (binding) = 5000 nM Inhibitory concentration of the compound against rat DHFR ChEMBL. 15974594
IC50 (binding) = 5000 nM Inhibitory activity of the compound against rat dihydrofolate reductase ChEMBL. 15026078
IC50 (binding) = 5000 nM Inhibitory concentration of the compound against rat DHFR ChEMBL. 15974594
Ratio (binding) = 150 Selectivity index was determined as ratio of IC50 against rat DHFR to that of IC50 against Toxoplasma gondii DHFR ChEMBL. 15026078
Ratio (binding) = 2100 Selectivity index was determined as ratio of IC50 against rat DHFR to that of IC50 against Mycobacterium avium DHFR ChEMBL. 15026078
Ratio (binding) = 5000 Selectivity index was determined as ratio of IC50 against rat DHFR to that of IC50 against Pneumocystis carinii DHFR ChEMBL. 15026078
Selectivity index (binding) = 150 Selectivity index measured as IC50(Rat)/IC50(T. gondii) ChEMBL. 15974594
Selectivity index (binding) = 2100 Selectivity index measured as IC50(Rat)/IC50(M. avium) ChEMBL. 15974594
Selectivity index (binding) = 5000 Selectivity index measured as IC50(Rat)/IC50(P. carnii) ChEMBL. 15974594

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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