Detailed information for compound 27034

Basic information

Technical information
  • TDR Targets ID: 27034
  • Name: 5-[[3-methoxy-4-(3-phenylpropoxy)phenyl]methy l]pyrimidine-2,4-diamine
  • MW: 364.441 | Formula: C21H24N4O2
  • H donors: 2 H acceptors: 2 LogP: 3.68 Rotable bonds: 8
    Rule of 5 violations (Lipinski): 1
  • SMILES: COc1cc(ccc1OCCCc1ccccc1)Cc1cnc(nc1N)N
  • InChi: 1S/C21H24N4O2/c1-26-19-13-16(12-17-14-24-21(23)25-20(17)22)9-10-18(19)27-11-5-8-15-6-3-2-4-7-15/h2-4,6-7,9-10,13-14H,5,8,11-12H2,1H3,(H4,22,23,24,25)
  • InChiKey: IJXHTJRYJGZEDE-UHFFFAOYSA-N  


Substructure search Similarity search

Network

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Synonyms

  • [2-amino-5-[3-methoxy-4-(3-phenylpropoxy)benzyl]pyrimidin-4-yl]amine
  • 5-{[3-Methoxy-4-(phenylpropoxy)phenyl]methyl}pyrimidine-2,4-diamine
  • AIDS-033125
  • AIDS033125

Targets

Known targets for this compound

Species Target name Source Bibliographic reference
Plasmodium falciparum bifunctional dihydrofolate reductase-thymidylate synthase Starlite/ChEMBL References

Predicted pathogen targets for this compound

By orthology
Species Potential target Known druggable target/s Ortholog Group
Leishmania mexicana 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
Plasmodium knowlesi bifunctional dihydrofolate reductase-thymidylate synthase, putative Get druggable targets OG5_127385 All targets in OG5_127385
Onchocerca volvulus 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 braziliensis 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
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
Plasmodium berghei bifunctional dihydrofolate reductase-thymidylate synthase, putative 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
Neospora caninum Bifunctional dihydrofolate reductase-thymidylate synthase, related 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
Trypanosoma brucei gambiense dihydrofolate reductase-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 leprae PROBABLE THYMIDYLATE SYNTHASE THYA (TS) (TSASE) 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 brucei dihydrofolate reductase-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
Mycobacterium ulcerans 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
Echinococcus granulosus 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
Schistosoma mansoni bifunctional 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
Plasmodium vivax bifunctional dihydrofolate reductase-thymidylate synthase, putative 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
Leishmania donovani dihydrofolate reductase-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
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) 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
By sequence similarity to non orthologous known druggable targets
No druggable targets predicted by sequence similarity
Obtained from network model

Ranking Plot

Putative Targets List

Species Potential target Raw Global Species
Trichomonas vaginalis conserved hypothetical protein 0.0062 0.2164 0.5
Onchocerca volvulus 0.013 0.6572 0.5
Trypanosoma cruzi dihydrofolate reductase-thymidylate synthase, putative 0.0062 0.2164 0.2164
Loa Loa (eye worm) thymidylate synthase 0.013 0.6572 1
Loa Loa (eye worm) dihydrofolate reductase 0.0053 0.1592 0.2423
Brugia malayi Cytochrome P450 family protein 0.006 0.204 0.3105
Echinococcus granulosus thymidylate synthase 0.013 0.6572 1
Toxoplasma gondii bifunctional dihydrofolate reductase-thymidylate synthase 0.0183 1 0.5
Plasmodium falciparum bifunctional dihydrofolate reductase-thymidylate synthase 0.0183 1 0.5
Mycobacterium tuberculosis Hypothetical protein 0.0062 0.2164 0.1148
Echinococcus multilocularis thymidylate synthase 0.013 0.6572 1
Brugia malayi Dihydrofolate reductase 0.0053 0.1592 0.2423
Mycobacterium ulcerans thymidylate synthase 0.013 0.6572 1
Loa Loa (eye worm) cytochrome P450 family protein 0.006 0.204 0.3105
Chlamydia trachomatis dihydrofolate reductase 0.0053 0.1592 0.5
Mycobacterium leprae PROBABLE THYMIDYLATE SYNTHASE THYA (TS) (TSASE) 0.013 0.6572 1
Trypanosoma brucei dihydrofolate reductase-thymidylate synthase 0.0183 1 1
Brugia malayi hypothetical protein 0.0062 0.2164 0.3292
Brugia malayi dihydrofolate reductase family protein 0.0053 0.1592 0.2423
Mycobacterium ulcerans dihydrofolate reductase DfrA 0.0053 0.1592 0.2423
Trypanosoma cruzi dihydrofolate reductase-thymidylate synthase 0.0183 1 1
Schistosoma mansoni bifunctional dihydrofolate reductase-thymidylate synthase 0.013 0.6572 1
Mycobacterium tuberculosis Probable thymidylate synthase ThyA (ts) (TSASE) 0.013 0.6572 1
Plasmodium vivax bifunctional dihydrofolate reductase-thymidylate synthase, putative 0.0183 1 0.5
Brugia malayi thymidylate synthase 0.013 0.6572 1

Activities

Activity type Activity value Assay description Source Reference
IC50 (functional) = 3 uM In vitro Antiplasmodial activity (IC50) against Plasmodium falciparum Clone with wild-type (TM4/8.2) ChEMBL. 11881993
IC50 (functional) = 3 uM In vitro Antiplasmodial activity (IC50) against Plasmodium falciparum Clone with wild-type (TM4/8.2) ChEMBL. 11881993
IC50 (functional) = 11.7 uM Antiplasmodial activity (IC50) against Plasmodium falciparum Clone with mutant enzyme C59R+S108N- pfDihydrofolate reductase (K1CB1) ChEMBL. 11881993
IC50 (functional) = 11.7 uM Antiplasmodial activity (IC50) against Plasmodium falciparum Clone with mutant enzyme C59R+S108N- pfDihydrofolate reductase (K1CB1) ChEMBL. 11881993
IC50 (functional) = 32 uM Cytotoxicity against human breast cancer cells. ChEMBL. 11881993
IC50 (functional) = 72 uM Cytotoxicity against human epidermoid carcinoma KB cell. ChEMBL. 11881993
IC50 (functional) = 72 uM Cytotoxicity against human epidermoid carcinoma KB cell. ChEMBL. 11881993
IC50 (functional) = 200 uM Cytotoxicity by the selective inhibition against African green monkey kidney fibroblast(vero cells). ChEMBL. 11881993
Ki (binding) = 1.8 nM Inhibitory activity against wild-type dihydrofolate reductase (S108N DHFR) ChEMBL. 14711307
Ki (binding) = 1.8 nM Inhibition of the wild-type dihydrofolate reductase (DHFR) ChEMBL. 11881993
Ki (binding) = 1.8 nM Inhibitory activity against wild-type dihydrofolate reductase (S108N DHFR) ChEMBL. 14711307
Ki (binding) = 1.8 nM Inhibition of the wild-type dihydrofolate reductase (DHFR) ChEMBL. 11881993
Ki (binding) = 26.6 nM Inhibition of the S108N mutant of dihydrofolate reductase (DHFR) ChEMBL. 11881993
Ki (binding) = 26.6 nM Inhibition of the S108N mutant of dihydrofolate reductase (DHFR) ChEMBL. 11881993
Ki (binding) = 44.2 nM Inhibitory activity against double mutant dihydrofolate reductase (C59R+S108N DHFR) ChEMBL. 14711307
Ki (binding) = 44.2 nM Inhibition of the C59R+S108N mutant of dihydrofolate reductase (DHFR) ChEMBL. 11881993
Ki (binding) = 44.2 nM Inhibitory activity against double mutant dihydrofolate reductase (C59R+S108N DHFR) ChEMBL. 14711307
Ki (binding) = 44.2 nM Inhibition of the C59R+S108N mutant of dihydrofolate reductase (DHFR) ChEMBL. 11881993
Ki (binding) = 1122.8 nM Inhibitory activity against quadruple mutant dihydrofolate reductase (N51I C59R S108N I164L DHFR) ChEMBL. 14711307
Ki (binding) = 1122.8 nM Inhibitory activity against quadruple mutant dihydrofolate reductase (N51I C59R S108N I164L DHFR) ChEMBL. 14711307
Ki (binding) = 3100.2 nM Inhibitory activity against triple mutant dihydrofolate reductase (C59R S108 NI164L DHFR) ChEMBL. 14711307
Ki (binding) = 3100.2 nM Inhibitory activity against triple mutant dihydrofolate reductase (C59R S108 NI164L DHFR) ChEMBL. 14711307
Ratio (functional) = 3.9 IC50 ratio of the compound (K1CB1/TM4) ChEMBL. 11881993
Ratio (binding) = 14.8 Ratio of Inhibition of the S108N mutant of dihydrofolate reductase (DHFR) to inhibition of wild type dihydrofolate reductase. ChEMBL. 11881993
Ratio (binding) = 224.5 Ratio of Inhibition of the C59R+S108N mutant of dihydrofolate reductase (DHFR) to inhibition of wild type dihydrofolate reductase. ChEMBL. 11881993
Ratio (functional) = 3.9 IC50 ratio of the compound (K1CB1/TM4) ChEMBL. 11881993
Ratio (binding) = 14.8 Ratio of Inhibition of the S108N mutant of dihydrofolate reductase (DHFR) to inhibition of wild type dihydrofolate reductase. ChEMBL. 11881993
Ratio (binding) = 224.5 Ratio of Inhibition of the C59R+S108N mutant of dihydrofolate reductase (DHFR) to inhibition of wild type dihydrofolate reductase. ChEMBL. 11881993
Relative activity (binding) = 0.17 Inhibitory activity against quadruple mutant dihydrofolate reductase (N51I C59R S108N I164L DHFR), relative to trimethoprim ChEMBL. 14711307
Relative activity (binding) = 0.17 Inhibitory activity against wild-type dihydrofolate reductase (S108N DHFR), relative to trimethoprim ChEMBL. 14711307
Relative activity (binding) = 0.2 Inhibition of S108N mutant dihydrofolate reductase (DHFR)relative to Tmp ChEMBL. 11881993
Relative activity (binding) = 0.2 Inhibition of the wild-type dihydrofolate reductase (DHFR) relative to Tmp ChEMBL. 11881993
Relative activity (binding) = 0.2 Inhibition of the C59R+S108N mutant of dihydrofolate reductase (DHFR)relative to Tmp ChEMBL. 11881993
Relative activity (binding) = 0.33 Inhibitory activity against double mutant dihydrofolate reductase (C59R S108N DHFR), relative to trimethoprim ChEMBL. 14711307
Relative activity (binding) = 0.54 Inhibitory activity against triple mutant dihydrofolate reductase (C59R S108 NI164L DHFR), relative to trimethoprim ChEMBL. 14711307
Relative activity (binding) = 0.17 Inhibitory activity against wild-type dihydrofolate reductase (S108N DHFR), relative to trimethoprim ChEMBL. 14711307
Relative activity (binding) = 0.17 Inhibitory activity against quadruple mutant dihydrofolate reductase (N51I C59R S108N I164L DHFR), relative to trimethoprim ChEMBL. 14711307
Relative activity (binding) = 0.2 Inhibition of the wild-type dihydrofolate reductase (DHFR) relative to Tmp ChEMBL. 11881993
Relative activity (binding) = 0.2 Inhibition of S108N mutant dihydrofolate reductase (DHFR)relative to Tmp ChEMBL. 11881993
Relative activity (binding) = 0.2 Inhibition of the C59R+S108N mutant of dihydrofolate reductase (DHFR)relative to Tmp ChEMBL. 11881993
Relative activity (binding) = 0.33 Inhibitory activity against double mutant dihydrofolate reductase (C59R S108N DHFR), relative to trimethoprim ChEMBL. 14711307
Relative activity (binding) = 0.54 Inhibitory activity against triple mutant dihydrofolate reductase (C59R S108 NI164L DHFR), relative to trimethoprim ChEMBL. 14711307
Safety ratio (functional) = 67 Safety ratio is cytotoxicity to vero cells/IC50 TM4. ChEMBL. 11881993
Safety ratio (functional) = 2.7 Safety ratio is cytotoxicity to BC cells/IC50 K1 ChEMBL. 11881993
Safety ratio (functional) = 6 Safety ratio is cytotoxicity to KB cells/IC50 K1 ChEMBL. 11881993
Safety ratio (functional) = 11 Safety ratio is cytotoxicity to BC cells/IC50 TM4. ChEMBL. 11881993
Safety ratio (functional) = 17 Safety ratio is cytotoxicity to vero cells/IC50 K1. ChEMBL. 11881993
Safety ratio (functional) = 24 Safety ratio is cytotoxicity to KB cells/IC50 TM4. ChEMBL. 11881993
Safety ratio (functional) = 67 Safety ratio is cytotoxicity to vero cells/IC50 TM4. ChEMBL. 11881993

Phenotypes

Whole-cell/tissue/organism interactions

Species name Source Reference Is orphan
Plasmodium falciparum ChEMBL23 11881993

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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