Detailed information for compound 331514

Basic information

Technical information
  • TDR Targets ID: 331514
  • Name: ethyl 5-[3-[(2,4-diamino-5-methylpyrido[2,3-d ]pyrimidin-6-yl)methyl]-4-methoxyphenoxy]pent anoate
  • MW: 439.507 | Formula: C23H29N5O4
  • H donors: 2 H acceptors: 4 LogP: 3.24 Rotable bonds: 11
    Rule of 5 violations (Lipinski): 1
  • SMILES: CCOC(=O)CCCCOc1ccc(c(c1)Cc1cnc2c(c1C)c(N)nc(n2)N)OC
  • InChi: 1S/C23H29N5O4/c1-4-31-19(29)7-5-6-10-32-17-8-9-18(30-3)15(12-17)11-16-13-26-22-20(14(16)2)21(24)27-23(25)28-22/h8-9,12-13H,4-7,10-11H2,1-3H3,(H4,24,25,26,27,28)
  • InChiKey: MXQNQGPRVZDOOS-UHFFFAOYSA-N  

Network

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Synonyms

  • ethyl 5-[3-[(2,4-diamino-5-methyl-pyrido[2,3-d]pyrimidin-6-yl)methyl]-4-methoxy-phenoxy]pentanoate
  • 5-[3-[(2,4-diamino-5-methyl-6-pyrido[2,3-d]pyrimidinyl)methyl]-4-methoxyphenoxy]pentanoic acid ethyl ester
  • ethyl 5-[3-[[2,4-bis(azanyl)-5-methyl-pyrido[2,3-d]pyrimidin-6-yl]methyl]-4-methoxy-phenoxy]pentanoate
  • 5-[3-[(2,4-diamino-5-methyl-pyrido[2,3-d]pyrimidin-6-yl)methyl]-4-methoxy-phenoxy]valeric acid ethyl ester
  • AIDS335725
  • Pentanoic acid, 5-[3-[(2,4-diamino-5-methylpyrido[2,3-d]pyrimidin-6-yl)methyl]-4-methoxyphenoxy]-, ethyl ester
  • AIDS-335725

Targets

Known targets for this compound

Species Target name Source Bibliographic reference
Pneumocystis carinii Dihydrofolate reductase Starlite/ChEMBL References
Mycobacterium avium Dihydrofolate reductase Starlite/ChEMBL References
Toxoplasma gondii bifunctional dihydrofolate reductase-thymidylate synthase 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
Neospora caninum Bifunctional dihydrofolate reductase-thymidylate synthase, related 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 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
Trypanosoma brucei 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
Loa Loa (eye worm) 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
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
Toxoplasma gondii 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
Leishmania mexicana dihydrofolate reductase-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
Echinococcus granulosus 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
Brugia malayi Dihydrofolate reductase 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
Chlamydia trachomatis dihydrofolate reductase Get druggable targets OG5_128410 All targets in OG5_128410
Candida albicans dihydrofolate reductase Get druggable targets OG5_128410 All targets in OG5_128410
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 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
Schistosoma japonicum hypothetical protein 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
Schistosoma japonicum ko:K00560 thymidylate synthase [EC2.1.1.45], putative 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 japonicum ko:K00287 dihydrofolate reductase [EC1.5.1.3], putative Get druggable targets OG5_128410 All targets in OG5_128410
Onchocerca volvulus 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
Theileria parva dihydrofolate reductase-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
Leishmania donovani dihydrofolate reductase-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
Candida albicans hypothetical protein Get druggable targets OG5_128410 All targets in OG5_128410
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
Mycobacterium tuberculosis Dihydrofolate reductase DfrA (DHFR) (tetrahydrofolate dehydrogenase) Get druggable targets OG5_128410 All targets in OG5_128410
Mycobacterium ulcerans 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

By sequence similarity to non orthologous known druggable targets
Species Potential target Known druggable target Length Alignment span Identity
Leishmania major dihydrofolate reductase-thymidylate synthase Dihydrofolate reductase   187 aa 172 aa 36.0 %
Plasmodium berghei bifunctional dihydrofolate reductase-thymidylate synthase, putative Dihydrofolate reductase   187 aa 211 aa 28.4 %
Leishmania braziliensis dihydrofolate reductase-thymidylate synthase Dihydrofolate reductase   187 aa 172 aa 34.3 %
Plasmodium vivax bifunctional dihydrofolate reductase-thymidylate synthase, putative Dihydrofolate reductase   187 aa 209 aa 29.2 %
Trypanosoma cruzi dihydrofolate reductase-thymidylate synthase Dihydrofolate reductase   206 aa 193 aa 29.5 %
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 %
Toxoplasma gondii bifunctional dihydrofolate reductase-thymidylate synthase Dihydrofolate reductase   187 aa 186 aa 37.1 %
Leishmania mexicana dihydrofolate reductase-thymidylate synthase Dihydrofolate reductase   187 aa 172 aa 33.7 %
Plasmodium knowlesi bifunctional dihydrofolate reductase-thymidylate synthase, putative Dihydrofolate reductase   187 aa 209 aa 29.2 %
Onchocerca volvulus Putative dihydrofolate reductase Dihydrofolate reductase   181 aa 174 aa 31.6 %
Leishmania donovani dihydrofolate reductase-thymidylate synthase Dihydrofolate reductase   187 aa 172 aa 36.0 %
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 %
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 falciparum bifunctional dihydrofolate reductase-thymidylate synthase Dihydrofolate reductase   187 aa 202 aa 29.2 %

Obtained from network model

Ranking Plot


Putative Targets List


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

Activities

Activity type Activity value Assay description Source Reference
IC50 (binding) = 9.4 nM Inhibitory concentration against Mycobacterium avium DHFR ChEMBL. 15974594
IC50 (binding) = 9.4 nM Inhibitory concentration against Mycobacterium avium DHFR ChEMBL. 15974594
IC50 (binding) = 11 nM Inhibitory concentration against Toxoplasma gondii DHFR ChEMBL. 15974594
IC50 (binding) = 11 nM Inhibitory concentration against Toxoplasma gondii DHFR ChEMBL. 15974594
IC50 (binding) = 14 nM Inhibitory concentration of the compound against rat DHFR ChEMBL. 15974594
IC50 (binding) = 14 nM Inhibitory concentration of the compound against rat DHFR ChEMBL. 15974594
IC50 (binding) = 28 nM Inhibitory concentration against Pneumocystis carinii DHFR ChEMBL. 15974594
IC50 (binding) = 28 nM Inhibitory concentration against Pneumocystis carinii DHFR ChEMBL. 15974594
Selectivity index (binding) = 0.5 Selectivity index measured as IC50(Rat)/IC50(P. carnii) ChEMBL. 15974594
Selectivity index (binding) = 1.3 Selectivity index measured as IC50(Rat)/IC50(T. gondii) ChEMBL. 15974594
Selectivity index (binding) = 1.5 Selectivity index measured as IC50(Rat)/IC50(M. avium) 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

1 literature reference was collected for this gene.

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