Detailed information for compound 1559312

Basic information

Technical information
  • Name: Unnamed compound
  • MW: 507.518 | Formula: C24H21N5O6S
  • H donors: 5 H acceptors: 6 LogP: 1.47 Rotable bonds: 8
    Rule of 5 violations (Lipinski): 2
  • SMILES: OC(=O)CC[C@H](N1Cc2c(C1=O)ccc(c2)NCc1cccc2c1c1c(=O)[nH]c(nc1s2)N)C(=O)O
  • InChi: 1S/C24H21N5O6S/c25-24-27-20(32)19-18-11(2-1-3-16(18)36-21(19)28-24)9-26-13-4-5-14-12(8-13)10-29(22(14)33)15(23(34)35)6-7-17(30)31/h1-5,8,15,26H,6-7,9-10H2,(H,30,31)(H,34,35)(H3,25,27,28,32)/t15-/m0/s1
  • InChiKey: QPDXRVRRCIFNSL-HNNXBMFYSA-N  

Network

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Synonyms

No synonyms found for this compound

Targets

Known targets for this compound

Species Target name Source Bibliographic reference
Homo sapiens dihydrofolate reductase Starlite/ChEMBL References
Escherichia coli Dihydrofolate reductase Starlite/ChEMBL References
Toxoplasma gondii bifunctional dihydrofolate reductase-thymidylate synthase Starlite/ChEMBL References
Homo sapiens thymidylate synthetase Starlite/ChEMBL References
Escherichia coli Thymidylate synthase (EC 2.1.1.45) (TS) (TSase) Starlite/ChEMBL References

Predicted pathogen targets for this compound

By orthology
Species Potential target Known druggable target/s Ortholog Group
Babesia bovis dihydrofolate reductase/thymidilate 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
Brugia malayi 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 japonicum ko:K00287 dihydrofolate reductase [EC1.5.1.3], putative Get druggable targets OG5_128410 All targets in OG5_128410
Leishmania infantum 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
Schistosoma mansoni bifunctional 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
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
Trypanosoma cruzi 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
Schistosoma japonicum hypothetical protein Get druggable targets OG5_127385 All targets in OG5_127385
Onchocerca volvulus 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
Cryptosporidium parvum 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 dihydrofolate reductase 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
Leishmania major 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
Mycobacterium tuberculosis Probable thymidylate synthase ThyA (ts) (TSASE) 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
Plasmodium berghei bifunctional dihydrofolate reductase-thymidylate synthase, putative 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 hypothetical protein Get druggable targets OG5_128410 All targets in OG5_128410
Echinococcus multilocularis 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
Echinococcus granulosus thymidylate synthase 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
Brugia malayi 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
Candida albicans Thymidylate synthase capable of functional substitution for S. cerevisiae CDC21 (YOR074C) Get druggable targets OG5_127385 All targets in OG5_127385
Chlamydia trachomatis 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
Mycobacterium leprae DIHYDROFOLATE REDUCTASE DFRA (DHFR) (TETRAHYDROFOLATE DEHYDROGENASE) 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
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
Toxoplasma gondii 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
Candida albicans Thymidylate synthase capable of functional substitution for S. cerevisiae CDC21 (YOR074C) 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

By sequence similarity to non orthologous known druggable targets
Species Potential target Known druggable target Length Alignment span Identity
Cryptosporidium hominis GDP-mannose pyrophosphorylase (4N40) Dihydrofolate reductase   157 aa 139 aa 28.1 %
Trypanosoma brucei dihydrofolate reductase-thymidylate synthase Dihydrofolate reductase   157 aa 156 aa 27.6 %
Cryptosporidium parvum mannose-1-phosphate guanylyltransferase Dihydrofolate reductase   157 aa 139 aa 27.3 %
Mycobacterium leprae DIHYDROFOLATE REDUCTASE DFRA (DHFR) (TETRAHYDROFOLATE DEHYDROGENASE) Dihydrofolate reductase   157 aa 158 aa 29.1 %
Plasmodium falciparum dihydrofolate synthase/folylpolyglutamate synthase Dihydrofolate reductase   157 aa 127 aa 19.7 %
Dictyostelium discoideum dihydrofolate reductase Dihydrofolate reductase   157 aa 146 aa 27.4 %
Trypanosoma cruzi ATP- dependent RNA helicase, putative Dihydrofolate reductase   157 aa 140 aa 22.9 %
Plasmodium falciparum bifunctional dihydrofolate reductase-thymidylate synthase dihydrofolate reductase 187 aa 202 aa 29.7 %
Candida albicans hypothetical protein Dihydrofolate reductase   157 aa 149 aa 29.5 %
Leishmania donovani serine carboxypeptidase (CBP1), putative Dihydrofolate reductase   157 aa 159 aa 23.3 %
Toxoplasma gondii bifunctional dihydrofolate reductase-thymidylate synthase Thymidylate synthase (EC 2.1.1.45) (TS) (TSase)   367 aa 361 aa 27.4 %
Plasmodium vivax bifunctional dihydrofolate reductase-thymidylate synthase, putative Thymidylate synthase (EC 2.1.1.45) (TS) (TSase)   367 aa 350 aa 25.7 %
Leishmania infantum serine carboxypeptidase (CBP1), putative,serine peptidase, Clan SC, Family S10 Dihydrofolate reductase   157 aa 159 aa 23.3 %
Candida albicans dihydrofolate reductase Dihydrofolate reductase   157 aa 149 aa 29.5 %
Plasmodium berghei bifunctional dihydrofolate reductase-thymidylate synthase, putative Thymidylate synthase (EC 2.1.1.45) (TS) (TSase)   367 aa 352 aa 25.9 %
Plasmodium vivax hypothetical protein, conserved Dihydrofolate reductase   157 aa 127 aa 26.8 %
Mycobacterium tuberculosis Dihydrofolate reductase DfrA (DHFR) (tetrahydrofolate dehydrogenase) Dihydrofolate reductase   157 aa 160 aa 29.4 %
Leishmania braziliensis dihydrofolate reductase-thymidylate synthase Dihydrofolate reductase   157 aa 172 aa 23.3 %
Leishmania major serine carboxypeptidase (CBP1), putative,serine peptidase, Clan SC, Family S10 Dihydrofolate reductase   157 aa 159 aa 21.4 %
Chlamydia trachomatis dihydrofolate reductase Dihydrofolate reductase   157 aa 133 aa 24.8 %
Trypanosoma cruzi dihydrofolate reductase-thymidylate synthase Dihydrofolate reductase   157 aa 137 aa 29.2 %
Babesia bovis dihydrofolate reductase/thymidilate synthase Dihydrofolate reductase   157 aa 178 aa 23.6 %
Leishmania infantum dihydrofolate reductase-thymidylate synthase Dihydrofolate reductase   157 aa 172 aa 23.3 %
Plasmodium knowlesi bifunctional dihydrofolate reductase-thymidylate synthase, putative Thymidylate synthase (EC 2.1.1.45) (TS) (TSase)   367 aa 352 aa 25.6 %
Leishmania major dihydrofolate reductase-thymidylate synthase Dihydrofolate reductase   157 aa 172 aa 23.8 %
Schistosoma mansoni dihydrofolate reductase Dihydrofolate reductase   157 aa 147 aa 28.6 %
Candida albicans dihydrofolate reductase Dihydrofolate reductase   157 aa 149 aa 29.5 %
Onchocerca volvulus Germline survival defective-1 homolog Dihydrofolate reductase   157 aa 165 aa 24.8 %
Trypanosoma brucei gambiense dihydrofolate reductase-thymidylate synthase Dihydrofolate reductase   157 aa 156 aa 27.6 %
Leishmania mexicana dihydrofolate reductase-thymidylate synthase Dihydrofolate reductase   157 aa 172 aa 23.8 %
Theileria parva dihydrofolate reductase-thymidylate synthase, putative Dihydrofolate reductase   157 aa 165 aa 24.2 %
Plasmodium yoelii thymidylate synthase, putative Thymidylate synthase (EC 2.1.1.45) (TS) (TSase)   367 aa 352 aa 25.6 %
Leishmania donovani dihydrofolate reductase-thymidylate synthase Dihydrofolate reductase   157 aa 172 aa 23.3 %
Onchocerca volvulus Putative dihydrofolate reductase Dihydrofolate reductase   157 aa 178 aa 23.6 %
Cryptosporidium hominis chain A, crystal structure of Dhfr Dihydrofolate reductase   157 aa 171 aa 32.2 %
Mycobacterium ulcerans dihydrofolate reductase DfrA Dihydrofolate reductase   157 aa 159 aa 28.3 %
Schistosoma mansoni bifunctional dihydrofolate reductase-thymidylate synthase Thymidylate synthase (EC 2.1.1.45) (TS) (TSase)   367 aa 373 aa 29.8 %
Neospora caninum Bifunctional dihydrofolate reductase-thymidylate synthase, related Thymidylate synthase (EC 2.1.1.45) (TS) (TSase)   367 aa 410 aa 24.4 %
Cryptosporidium parvum dihydrofolate reductase-thymidylate synthase Dihydrofolate reductase   157 aa 169 aa 32.0 %
Plasmodium falciparum bifunctional dihydrofolate reductase-thymidylate synthase Thymidylate synthase (EC 2.1.1.45) (TS) (TSase)   367 aa 352 aa 25.9 %
Plasmodium yoelii hypothetical protein Dihydrofolate reductase   157 aa 132 aa 24.2 %

Obtained from network model

Ranking Plot


Putative Targets List


Species Potential target Raw Global Species
Toxoplasma gondii bifunctional dihydrofolate reductase-thymidylate synthase 0.0721 1 0.5
Brugia malayi thymidylate synthase 0.051 0.6254 1
Trypanosoma cruzi dihydrofolate reductase-thymidylate synthase 0.0721 1 1
Echinococcus multilocularis thymidylate synthase 0.051 0.6254 1
Mycobacterium tuberculosis Probable thymidylate synthase ThyA (ts) (TSASE) 0.051 0.6254 1
Schistosoma mansoni bifunctional dihydrofolate reductase-thymidylate synthase 0.051 0.6254 1
Trypanosoma brucei dihydrofolate reductase-thymidylate synthase 0.0721 1 0.5
Brugia malayi dihydrofolate reductase family protein 0.034 0.325 0.3053
Brugia malayi Dihydrofolate reductase 0.034 0.325 0.3053
Loa Loa (eye worm) thymidylate synthase 0.051 0.6254 1
Trichomonas vaginalis conserved hypothetical protein 0.034 0.3244 0.5
Chlamydia trachomatis dihydrofolate reductase 0.034 0.325 0.5
Mycobacterium ulcerans thymidylate synthase 0.051 0.6254 1
Schistosoma mansoni dihydrofolate reductase 0.034 0.325 0.5197
Plasmodium falciparum bifunctional dihydrofolate reductase-thymidylate synthase 0.0721 1 0.5
Brugia malayi hypothetical protein 0.034 0.3244 0.304
Loa Loa (eye worm) dihydrofolate reductase 0.034 0.325 0.3053
Plasmodium vivax bifunctional dihydrofolate reductase-thymidylate synthase, putative 0.0721 1 0.5
Onchocerca volvulus 0.051 0.6254 0.5
Echinococcus granulosus thymidylate synthase 0.051 0.6254 1
Echinococcus granulosus dihydrofolate reductase 0.034 0.325 0.4579
Mycobacterium tuberculosis Dihydrofolate reductase DfrA (DHFR) (tetrahydrofolate dehydrogenase) 0.034 0.325 0.002
Mycobacterium leprae PROBABLE THYMIDYLATE SYNTHASE THYA (TS) (TSASE) 0.051 0.6254 1
Echinococcus multilocularis dihydrofolate reductase 0.034 0.325 0.4579

Activities

Activity type Activity value Assay description Source Reference
IC50 (binding) = 0.01 uM Inhibition of Toxoplasma gondii DHFR by spectrophotometry ChEMBL. 21550809
IC50 (binding) = 0.034 uM Inhibition of human TS assessed as oxidation of tetrahydrofolate to dihydrofolate after 2 to 12 mins by spectrophotometry ChEMBL. 21550809
IC50 (binding) = 0.05 uM Inhibition of Escherichia coli TS assessed as oxidation of tetrahydrofolate to dihydrofolate after 2 to 12 mins by spectrophotometry ChEMBL. 21550809
IC50 (binding) = 0.1 uM Inhibition of human DHFR by spectrophotometry ChEMBL. 21550809
IC50 (binding) = 0.17 uM Inhibition of Toxoplasma gondii TS assessed as oxidation of tetrahydrofolate to dihydrofolate after 2 to 12 mins by spectrophotometry ChEMBL. 21550809
IC50 (binding) = 0.4 uM Inhibition of Escherichia coli DHFR by spectrophotometry ChEMBL. 21550809
Ratio IC50 (binding) = 50 Ratio of premetrexed IC50 to compound IC50 for human TS ChEMBL. 21550809

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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