Detailed information for compound 449119

Basic information

Technical information
  • TDR Targets ID: 449119
  • Name: 1-[4-chloro-3-(trifluoromethyl)phenyl]-3-[[(2 R,3S,5S)-3-hydroxy-5-(5-methyl-2,4-dioxopyrim idin-1-yl)oxolan-2-yl]methyl]urea
  • MW: 462.808 | Formula: C18H18ClF3N4O5
  • H donors: 4 H acceptors: 4 LogP: 1.94 Rotable bonds: 7
    Rule of 5 violations (Lipinski): 1
  • SMILES: O=C(Nc1ccc(c(c1)C(F)(F)F)Cl)NC[C@H]1O[C@@H](C[C@@H]1O)n1cc(C)c(=O)[nH]c1=O
  • InChi: 1S/C18H18ClF3N4O5/c1-8-7-26(17(30)25-15(8)28)14-5-12(27)13(31-14)6-23-16(29)24-9-2-3-11(19)10(4-9)18(20,21)22/h2-4,7,12-14,27H,5-6H2,1H3,(H2,23,24,29)(H,25,28,30)/t12-,13+,14-/m0/s1
  • InChiKey: FIFLVFXOJCAQLR-MJBXVCDLSA-N  


Substructure search Similarity search

Network

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Synonyms

  • 1-[4-chloro-3-(trifluoromethyl)phenyl]-3-[[(2R,3S,5S)-3-hydroxy-5-(5-methyl-2,4-dioxo-pyrimidin-1-yl)tetrahydrofuran-2-yl]methyl]urea
  • 1-[4-chloro-3-(trifluoromethyl)phenyl]-3-[[(2R,3S,5S)-3-hydroxy-5-(5-methyl-2,4-dioxo-1-pyrimidinyl)-2-tetrahydrofuranyl]methyl]urea
  • 1-[4-chloro-3-(trifluoromethyl)phenyl]-3-[[(2R,3S,5S)-3-hydroxy-5-(5-methyl-2,4-dioxo-pyrimidin-1-yl)oxolan-2-yl]methyl]urea
  • 1-[4-chloro-3-(trifluoromethyl)phenyl]-3-[[(2R,3S,5S)-5-(2,4-diketo-5-methyl-pyrimidin-1-yl)-3-hydroxy-tetrahydrofuran-2-yl]methyl]urea
  • 3-[4-chloro-3-(trifluoromethyl)phenyl]-1-[[(2R,3S,5S)-3-hydroxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methyl]urea
  • 3-[4-chloro-3-(trifluoromethyl)phenyl]-1-[[(2R,3S,5S)-3-hydroxy-5-(5-methyl-2,4-dioxo-pyrimidin-1-yl)tetrahydrofuran-2-yl]methyl]urea
  • 3-[4-chloro-3-(trifluoromethyl)phenyl]-1-[[(2R,3S,5S)-3-hydroxy-5-(5-methyl-2,4-dioxo-1-pyrimidinyl)-2-tetrahydrofuranyl]methyl]urea
  • 3-[4-chloro-3-(trifluoromethyl)phenyl]-1-[[(2R,3S,5S)-5-(2,4-diketo-5-methyl-pyrimidin-1-yl)-3-hydroxy-tetrahydrofuran-2-yl]methyl]urea
  • 3-[4-chloro-3-(trifluoromethyl)phenyl]-1-[[(2R,3S,5S)-3-hydroxy-5-(5-methyl-2,4-dioxo-pyrimidin-1-yl)oxolan-2-yl]methyl]urea

Targets

Known targets for this compound

Species Target name Source Bibliographic reference
Mycobacterium tuberculosis Thymidylate kinase Tmk (dTMP kinase) (thymidylic acid kinase) (TMPK) References

Predicted pathogen targets for this compound

By orthology
Species Potential target Known druggable target/s Ortholog Group
Trypanosoma congolense thymidylate kinase, putative Get druggable targets OG5_126920 All targets in OG5_126920
Trypanosoma cruzi thymidylate kinase, putative Get druggable targets OG5_126920 All targets in OG5_126920
Cryptosporidium parvum thymidylate kinase Get druggable targets OG5_126920 All targets in OG5_126920
Theileria parva thymidylate kinase, putative Get druggable targets OG5_126920 All targets in OG5_126920
Plasmodium yoelii Thymidylate kinase Get druggable targets OG5_126920 All targets in OG5_126920
Trypanosoma brucei thymidylate kinase, putative Get druggable targets OG5_126920 All targets in OG5_126920
Chlamydia trachomatis thymidylate kinase Get druggable targets OG5_126920 All targets in OG5_126920
Mycobacterium ulcerans thymidylate kinase Get druggable targets OG5_126920 All targets in OG5_126920
Neospora caninum Thymidylate kinase, related Get druggable targets OG5_126920 All targets in OG5_126920
Trypanosoma brucei gambiense thymidylate kinase, putative Get druggable targets OG5_126920 All targets in OG5_126920
Mycobacterium tuberculosis Thymidylate kinase Tmk (dTMP kinase) (thymidylic acid kinase) (TMPK) Get druggable targets OG5_126920 All targets in OG5_126920
Babesia bovis thymidylate kinase, putative Get druggable targets OG5_126920 All targets in OG5_126920
Onchocerca volvulus Putative thymidylate kinase Get druggable targets OG5_126920 All targets in OG5_126920
Trichomonas vaginalis thymidylate kinase, putative Get druggable targets OG5_126920 All targets in OG5_126920
Candida albicans Thymidylate kinase Get druggable targets OG5_126920 All targets in OG5_126920
Plasmodium vivax thymidylate kinase, putative Get druggable targets OG5_126920 All targets in OG5_126920
Leishmania infantum thymidylate kinase-like protein Get druggable targets OG5_126920 All targets in OG5_126920
Mycobacterium leprae probable thymidylate kinase Tmk (dTMP KINASE) (THYMIDYLIC ACID KINASE) (TMPK) Get druggable targets OG5_126920 All targets in OG5_126920
Loa Loa (eye worm) thymidylate kinase Get druggable targets OG5_126920 All targets in OG5_126920
Echinococcus granulosus thymidylate kinase Get druggable targets OG5_126920 All targets in OG5_126920
Schistosoma mansoni hypothetical protein Get druggable targets OG5_126920 All targets in OG5_126920
Schistosoma japonicum Thymidylate kinase, putative Get druggable targets OG5_126920 All targets in OG5_126920
Cryptosporidium hominis thymidylate kinase Get druggable targets OG5_126920 All targets in OG5_126920
Candida albicans Thymidylate kinase Get druggable targets OG5_126920 All targets in OG5_126920
Brugia malayi thymidylate kinase Get druggable targets OG5_126920 All targets in OG5_126920
Schistosoma japonicum ko:K00943 dTMP kinase [EC2.7.4.9], putative Get druggable targets OG5_126920 All targets in OG5_126920
Schistosoma mansoni thymidylate kinase Get druggable targets OG5_126920 All targets in OG5_126920
Schistosoma mansoni thymidylate kinase Get druggable targets OG5_126920 All targets in OG5_126920
Entamoeba histolytica Thymidylate kinase, putative Get druggable targets OG5_126920 All targets in OG5_126920
Leishmania braziliensis thymidylate kinase-like protein Get druggable targets OG5_126920 All targets in OG5_126920
Leishmania mexicana thymidylate kinase-like protein Get druggable targets OG5_126920 All targets in OG5_126920
Trypanosoma cruzi thymidylate kinase, putative Get druggable targets OG5_126920 All targets in OG5_126920
Echinococcus multilocularis thymidylate kinase Get druggable targets OG5_126920 All targets in OG5_126920
Plasmodium falciparum thymidylate kinase Get druggable targets OG5_126920 All targets in OG5_126920
Toxoplasma gondii thymidylate kinase Get druggable targets OG5_126920 All targets in OG5_126920
Treponema pallidum thymidylate kinase (tmk) Get druggable targets OG5_126920 All targets in OG5_126920
Plasmodium berghei thymidylate kinase, putative Get druggable targets OG5_126920 All targets in OG5_126920
Trypanosoma congolense thymidylate kinase, putative Get druggable targets OG5_126920 All targets in OG5_126920
Wolbachia endosymbiont of Brugia malayi thymidylate kinase Get druggable targets OG5_126920 All targets in OG5_126920
Leishmania donovani thymidylate kinase-like protein Get druggable targets OG5_126920 All targets in OG5_126920
Trypanosoma brucei thymidylate kinase, putative Get druggable targets OG5_126920 All targets in OG5_126920
Leishmania major thymidylate kinase-like protein Get druggable targets OG5_126920 All targets in OG5_126920
Trichomonas vaginalis thymidylate kinase, putative Get druggable targets OG5_126920 All targets in OG5_126920
Plasmodium knowlesi thymidylate kinase, putative Get druggable targets OG5_126920 All targets in OG5_126920
Giardia lamblia CDC8 Get druggable targets OG5_126920 All targets in OG5_126920
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
Schistosoma mansoni inhibitor of apoptosis protein 0.101161 0.965255 0.964952
Mycobacterium tuberculosis Thymidylate kinase Tmk (dTMP kinase) (thymidylic acid kinase) (TMPK) 0.0118041 0.0712323 0.5
Echinococcus granulosus inhibitor of apoptosis protein 0.101161 0.965255 0.964952
Brugia malayi hypothetical protein 0.0312435 0.265725 0.259316
Schistosoma mansoni cathepsin B-like peptidase (C01 family) 0.0454534 0.407896 0.402728
Trypanosoma cruzi metallo-peptidase, Clan MG, Family M24 0.00554938 0.00865301 0.00865301
Schistosoma mansoni thymidylate kinase 0.0118041 0.0712323 0.0631255
Loa Loa (eye worm) hypothetical protein 0.104634 1 1
Echinococcus multilocularis cathepsin b 0.104634 1 1
Schistosoma mansoni hypothetical protein 0.0118041 0.0712323 0.0631255
Leishmania major methionine aminopeptidase 2, putative 0.00554938 0.00865301 0.0212138
Echinococcus granulosus thymidylate kinase 0.0118041 0.0712323 0.0631255
Trypanosoma brucei cysteine peptidase C (CPC) 0.0454534 0.407896 1
Echinococcus multilocularis caspase 2 0.0312435 0.265725 0.259316
Loa Loa (eye worm) hypothetical protein 0.0312435 0.265725 0.259316
Schistosoma mansoni inhibitor of apoptosis (iap) domain family member 0.101161 0.965255 0.964952
Loa Loa (eye worm) hypothetical protein 0.101161 0.965255 0.964952
Echinococcus multilocularis inhibitor of apoptosis protein 0.101161 0.965255 0.964952
Echinococcus granulosus apoptotic protease activating factor 1 0.0312435 0.265725 0.259316
Trypanosoma cruzi thymidylate kinase, putative 0.0118041 0.0712323 0.0712323
Trichomonas vaginalis Clan CA, family C1, cathepsin B-like cysteine peptidase 0.0454534 0.407896 1
Brugia malayi Inhibitor of Apoptosis domain containing protein 0.101161 0.965255 0.964952
Brugia malayi cathepsin B-like cysteine proteinase 0.104634 1 1
Echinococcus multilocularis baculoviral IAP repeat containing protein 0.101161 0.965255 0.964952
Echinococcus granulosus cathepsin b 0.104634 1 1
Leishmania major cysteine peptidase C (CPC),CPC cysteine peptidase, Clan CA, family C1, Cathepsin B-like 0.0454534 0.407896 1
Toxoplasma gondii thymidylate kinase 0.0118041 0.0712323 0.156745
Toxoplasma gondii cathepsin B 0.0454534 0.407896 1
Loa Loa (eye worm) cathepsin B 0.0454534 0.407896 0.402728
Trypanosoma cruzi cysteine peptidase C (CPC), putative 0.104634 1 1
Echinococcus granulosus baculoviral IAP repeat containing protein 0.101161 0.965255 0.964952
Trypanosoma brucei thymidylate kinase, putative 0.0118041 0.0712323 0.156745
Schistosoma mansoni cathepsin B-like peptidase (C01 family) 0.104634 1 1
Trypanosoma brucei thymidylate kinase, putative 0.0118041 0.0712323 0.156745
Plasmodium vivax thymidylate kinase, putative 0.0118041 0.0712323 1
Onchocerca volvulus 0.0312435 0.265725 0.268735
Trichomonas vaginalis thymidylate kinase, putative 0.0118041 0.0712323 0.156745
Giardia lamblia CDC8 0.0118041 0.0712323 0.156745
Echinococcus multilocularis cathepsin b 0.104634 1 1
Giardia lamblia Cathepsin B precursor 0.0454534 0.407896 1
Trypanosoma cruzi cysteine peptidase C (CPC), putative 0.0454534 0.407896 0.407896
Schistosoma mansoni SmCB2 peptidase (C01 family) 0.104634 1 1
Leishmania major thymidylate kinase-like protein 0.0118041 0.0712323 0.174633
Giardia lamblia Cathepsin B precursor 0.0454534 0.407896 1
Mycobacterium ulcerans thymidylate kinase 0.0118041 0.0712323 0.5
Trypanosoma cruzi thymidylate kinase, putative 0.0118041 0.0712323 0.0712323
Schistosoma mansoni cathepsin B-like peptidase (C01 family) 0.104634 1 1
Mycobacterium leprae probable thymidylate kinase Tmk (dTMP KINASE) (THYMIDYLIC ACID KINASE) (TMPK) 0.0118041 0.0712323 0.5
Echinococcus granulosus cathepsin b 0.104634 1 1
Wolbachia endosymbiont of Brugia malayi thymidylate kinase 0.0118041 0.0712323 0.5
Trypanosoma cruzi metallo-peptidase, Clan MG, Family M24 0.00554938 0.00865301 0.00865301
Echinococcus multilocularis apoptotic protease activating factor 1 0.0312435 0.265725 0.259316
Echinococcus multilocularis thymidylate kinase 0.0118041 0.0712323 0.0631255
Schistosoma mansoni caspase-7 (C14 family) 0.0312435 0.265725 0.259316
Loa Loa (eye worm) thymidylate kinase 0.0118041 0.0712323 0.0631255
Trichomonas vaginalis thymidylate kinase, putative 0.0118041 0.0712323 0.156745
Onchocerca volvulus Putative thymidylate kinase 0.0118041 0.0712323 0.0654183
Onchocerca volvulus Cell death protein 3 homolog 0.0312435 0.265725 0.268735
Onchocerca volvulus 0.101161 0.965255 1
Echinococcus granulosus caspase 2 0.0312435 0.265725 0.259316
Plasmodium falciparum thymidylate kinase 0.0118041 0.0712323 1
Chlamydia trachomatis thymidylate kinase 0.0118041 0.0712323 0.5
Schistosoma mansoni hypothetical protein 0.0312435 0.265725 0.259316
Brugia malayi Inhibitor of Apoptosis domain containing protein 0.101161 0.965255 0.964952
Schistosoma mansoni cathepsin B-like peptidase (C01 family) 0.104634 1 1
Loa Loa (eye worm) hypothetical protein 0.0312435 0.265725 0.259316
Brugia malayi Cell death protein 3 precursor 0.0312435 0.265725 0.259316
Schistosoma mansoni thymidylate kinase 0.0118041 0.0712323 0.0631255
Treponema pallidum thymidylate kinase (tmk) 0.0118041 0.0712323 0.5
Schistosoma mansoni hypothetical protein 0.101161 0.965255 0.964952
Onchocerca volvulus Deterin homolog 0.101161 0.965255 1
Giardia lamblia Cathepsin B precursor 0.0454534 0.407896 1
Entamoeba histolytica Thymidylate kinase, putative 0.0118041 0.0712323 1
Brugia malayi thymidylate kinase 0.0118041 0.0712323 0.0631255
Loa Loa (eye worm) hypothetical protein 0.101161 0.965255 0.964952

Activities

Activity type Activity value Assay description Source Reference
CC50 (ADMET) > 50 uM Cytotoxicity against human MRC5 cells ChEMBL. 23240776
EC50 (functional) = 9 uM Antimalarial activity against erythrocytic stages of Plasmodium falciparum 3D7 infected in human O positive RBC after 48 hrs by SYBR-green assay ChEMBL. 23240776
Inhibition (functional) = 49 % Growth inhibition of Mycobacterium tuberculosis H37Rv at 6.25 ug/mL by MABA assay ChEMBL. 17910427
Inhibition (functional) = 49 % Growth inhibition of Mycobacterium tuberculosis H37Rv at 6.25 ug/mL by MABA assay ChEMBL. 17910427
Ki (binding) = 1.9 uM Inhibition of Mycobacterium tuberculosis TMPK expressed in Escherichia coli by spectrophotometric assay ChEMBL. 17910427
Ki (binding) = 1.9 uM Inhibition of Mycobacterium tuberculosis TMPK expressed in Escherichia coli by spectrophotometric assay ChEMBL. 17910427
Ki (binding) = 88 uM Inhibition of recombinant Plasmodium falciparum TMPK using TMP as substrate by pyruvate kinase and lactate dehydrogenase enzyme coupled assay ChEMBL. 23240776
Ki (binding) = 166 uM Inhibition of human TMPK expressed in Escherichia coli by spectrophotometric assay ChEMBL. 17910427
MIC50 (functional) = 40 ug ml-1 Growth inhibition of Mycobacterium bovis BCG 1173P2 ChEMBL. 17910427
Ratio Ki (binding) = 90 Selectivity ratio of Ki for Mycobacterium tuberculosis TMPK to Ki for human TMPK ChEMBL. 17910427

Phenotypes

Whole-cell/tissue/organism interactions

Species name Source Reference Is orphan
Plasmodium falciparum ChEMBL23 23240776

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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