Detailed information for compound 274122

Basic information

Technical information
  • TDR Targets ID: 274122
  • Name: 3-[2,6-diamino-5-(3-chlorophenyl)pyrimidin-4- yl]propyl acetate
  • MW: 320.774 | Formula: C15H17ClN4O2
  • H donors: 2 H acceptors: 3 LogP: 2.3 Rotable bonds: 6
    Rule of 5 violations (Lipinski): 1
  • SMILES: CC(=O)OCCCc1nc(N)nc(c1c1cccc(c1)Cl)N
  • InChi: 1S/C15H17ClN4O2/c1-9(21)22-7-3-6-12-13(14(17)20-15(18)19-12)10-4-2-5-11(16)8-10/h2,4-5,8H,3,6-7H2,1H3,(H4,17,18,19,20)
  • InChiKey: YRAOVTHKXFGTRW-UHFFFAOYSA-N  

Network

Hover on a compound node to display the structore

Synonyms

  • acetic acid 3-[2,6-diamino-5-(3-chlorophenyl)-4-pyrimidinyl]propyl ester
  • 3-[2,6-bis(azanyl)-5-(3-chlorophenyl)pyrimidin-4-yl]propyl ethanoate
  • acetic acid 3-[2,6-diamino-5-(3-chlorophenyl)pyrimidin-4-yl]propyl ester
  • 3-[2,6-diamino-5-(3-chlorophenyl)pyrimidin-4-yl]propyl ethanoate

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
Plasmodium knowlesi 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
Cryptosporidium parvum 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
Leishmania donovani 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
Loa Loa (eye worm) thymidylate synthase 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
Echinococcus granulosus 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
Toxoplasma gondii bifunctional dihydrofolate reductase-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
Trypanosoma cruzi 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
Leishmania infantum dihydrofolate reductase-thymidylate synthase Get druggable targets OG5_127385 All targets in OG5_127385
Onchocerca volvulus Get druggable targets OG5_127385 All targets in OG5_127385
Brugia malayi 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
Plasmodium vivax 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
Schistosoma japonicum hypothetical protein 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
Leishmania braziliensis 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 falciparum bifunctional 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
Mycobacterium ulcerans 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
Mycobacterium leprae PROBABLE THYMIDYLATE SYNTHASE THYA (TS) (TSASE) 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 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

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
Echinococcus granulosus thymidylate synthase 0.013 0.5087 1
Toxoplasma gondii bifunctional dihydrofolate reductase-thymidylate synthase 0.0183 1 0.5
Onchocerca volvulus 0.013 0.5087 1
Loa Loa (eye worm) thymidylate synthase 0.013 0.5087 1
Mycobacterium ulcerans thymidylate synthase 0.013 0.5087 0.5
Echinococcus multilocularis thymidylate synthase 0.013 0.5087 1
Plasmodium vivax bifunctional dihydrofolate reductase-thymidylate synthase, putative 0.0183 1 0.5
Schistosoma mansoni bifunctional dihydrofolate reductase-thymidylate synthase 0.013 0.5087 1
Mycobacterium leprae PROBABLE THYMIDYLATE SYNTHASE THYA (TS) (TSASE) 0.013 0.5087 0.5
Trypanosoma brucei dihydrofolate reductase-thymidylate synthase 0.0183 1 0.5
Mycobacterium tuberculosis Probable thymidylate synthase ThyA (ts) (TSASE) 0.013 0.5087 0.5
Trypanosoma cruzi dihydrofolate reductase-thymidylate synthase 0.0183 1 0.5
Brugia malayi thymidylate synthase 0.013 0.5087 1
Plasmodium falciparum bifunctional dihydrofolate reductase-thymidylate synthase 0.0183 1 0.5

Activities

Activity type Activity value Assay description Source Reference
IC50 (functional) = 1.6 uM In vitro anti-plasmodial activity against Plasmodium falciparum with wild type dihydrofolate reductase (TM4/8.2). ChEMBL. 14736247
IC50 (functional) = 1.6 uM In vitro anti-plasmodial activity against Plasmodium falciparum with wild type dihydrofolate reductase (TM4/8.2). ChEMBL. 14736247
IC50 (functional) = 1.8 uM In vitro anti-plasmodial activity against Plasmodium falciparum with mutant C59R+S108N+I164L (Csl-2) dihydrofolate reductase. ChEMBL. 14736247
IC50 (functional) = 1.8 uM In vitro anti-plasmodial activity against Plasmodium falciparum with mutant C59R+S108N+I164L (Csl-2) dihydrofolate reductase. ChEMBL. 14736247
IC50 (functional) = 2 uM Antimicrobial activity against Plasmodium falciparum ChEMBL. 20185316
IC50 (functional) = 2.1 uM In vitro anti-plasmodial activity against Plasmodium falciparum with mutant N51I+C59R+S108N (W2) dihydrofolate reductase. ChEMBL. 14736247
IC50 (functional) = 2.1 uM In vitro anti-plasmodial activity against Plasmodium falciparum with mutant N51I+C59R+S108N (W2) dihydrofolate reductase. ChEMBL. 14736247
IC50 (functional) = 5.3 uM In vitro anti-plasmodial activity against Plasmodium falciparum with mutant CN51I+C59R+S108N+I164L (V1/S) dihydrofolate reductase. ChEMBL. 14736247
IC50 (functional) = 5.3 uM In vitro anti-plasmodial activity against Plasmodium falciparum with mutant CN51I+C59R+S108N+I164L (V1/S) dihydrofolate reductase. ChEMBL. 14736247
IC50 (functional) = 10 uM In vitro cytotoxicity against Plasmodium falciparum infected BC cell line. ChEMBL. 14736247
IC50 (functional) = 17 uM In vitro cytotoxicity against Plasmodium falciparum infected KB cell line ChEMBL. 14736247
IC50 (functional) = 17 uM In vitro cytotoxicity against Plasmodium falciparum infected KB cell line ChEMBL. 14736247
IC50 (functional) = 50 uM In vitro cytotoxicity against Plasmodium falciparum infected vero cell line. ChEMBL. 14736247
Ki (binding) = 1.8 nM Binding affinity towards mutant dihydrofolate reductase (N51I+C59R+S108N DHFR) of Plasmodium falciparum ChEMBL. 14736247
Ki (binding) = 1.8 nM Binding affinity towards mutant dihydrofolate reductase (N51I+C59R+S108N DHFR) of Plasmodium falciparum ChEMBL. 14736247
Ki (binding) = 3.1 nM Binding affinity towards wild-type dihydrofolate reductase of Plasmodium falciparum. ChEMBL. 14736247
Ki (binding) = 3.1 nM Binding affinity towards wild-type dihydrofolate reductase of Plasmodium falciparum. ChEMBL. 14736247
Ki (binding) = 3.2 nM Binding affinity towards mutant dihydrofolate reductase (C59R+S108N+I164L DHFR) of Plasmodium falciparum ChEMBL. 14736247
Ki (binding) = 3.2 nM Binding affinity towards mutant dihydrofolate reductase (C59R+S108N+I164L DHFR) of Plasmodium falciparum ChEMBL. 14736247
Ki (binding) = 31.4 nM Binding affinity towards mutant dihydrofolate reductase (N51I+C59R+S108N+I164L DHFR) of Plasmodium falciparum ChEMBL. 14736247
Ki (binding) = 31.4 nM Binding affinity towards mutant dihydrofolate reductase (N51I+C59R+S108N+I164L DHFR) of Plasmodium falciparum ChEMBL. 14736247
Ratio (binding) = 0.6 Ratio of binding affinity of compound for mutant (N51I+C59R+S108N) to that of wild type dihydrofolate reductase ChEMBL. 14736247
Ratio (binding) = 1 Ratio of binding affinity of compound for mutant (C59R+S108N+I164L) to that of wild type dihydrofolate reductase ChEMBL. 14736247
Ratio (binding) = 10.1 Ratio of binding affinity of compound for mutant (N51I+C59R+S108N+I164L) to that of wild type dihydrofolate reductase ChEMBL. 14736247
Ratio (binding) = 0.6 Ratio of binding affinity of compound for mutant (N51I+C59R+S108N) to that of wild type dihydrofolate reductase ChEMBL. 14736247
Ratio (binding) = 1 Ratio of binding affinity of compound for mutant (C59R+S108N+I164L) to that of wild type dihydrofolate reductase ChEMBL. 14736247
Ratio (binding) = 10.1 Ratio of binding affinity of compound for mutant (N51I+C59R+S108N+I164L) to that of wild type dihydrofolate reductase ChEMBL. 14736247
Safety ratio (functional) = 1.9 Ratio of cytotoxicity to that of anti-plasmodial activity against Plasmodium falciparum (V1/S) infected BC cell line ChEMBL. 14736247
Safety ratio (functional) = 3.2 Ratio of cytotoxicity to that of anti-plasmodial activity against Plasmodium falciparum (V1/S) infected KB cell line ChEMBL. 14736247
Safety ratio (functional) = 5.6 Ratio of cytotoxicity to that of anti-plasmodial activity against Plasmodium falciparum (Csl-2) infected BC cell line ChEMBL. 14736247
Safety ratio (functional) = 6.3 Ratio of cytotoxicity to that of anti-plasmodial activity against Plasmodium falciparum (TM4/8.2) infected BC cell line ChEMBL. 14736247
Safety ratio (functional) = 9.4 Ratio of cytotoxicity to that of anti-plasmodial activity against Plasmodium falciparum (V1/S) infected vero cell line ChEMBL. 14736247
Safety ratio (functional) = 9.4 Ratio of cytotoxicity to that of anti-plasmodial activity against Plasmodium falciparum (Csl-2) infected KB cell line ChEMBL. 14736247
Safety ratio (functional) = 10.6 Ratio of cytotoxicity to that of anti-plasmodial activity against Plasmodium falciparum (TM4/8.2) infected KB cell line ChEMBL. 14736247
Safety ratio (functional) = 27.8 Ratio of cytotoxicity to that of anti-plasmodial activity against Plasmodium falciparum (Csl-2) infected vero cell line ChEMBL. 14736247
Safety ratio (functional) = 31.3 Ratio of cytotoxicity versus anti-plasmodial activity against Plasmodium falciparum (TM4/8.2) infected vero cell line ChEMBL. 14736247

Phenotypes

Whole-cell/tissue/organism interactions

Species name Source Reference Is orphan
Plasmodium falciparum ChEMBL23 20185316
Homo sapiens ChEMBL23 14736247

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.

If you have references for this compound, please enter them in a user comment (below) or Contact us.