TDR Targets

Basic information

Technical information

Name: Unnamed compound
MW: 344.41 | Formula: C21H20N4O
H donors: 2 H acceptors: 2 LogP: 4.42 Rotable bonds: 3
Rule of 5 violations (Lipinski): 1
SMILES: CCOc1ccc2c(c1c1cc3nc(N)nc(c3cc1C)N)cccc2
InChi: 1S/C21H20N4O/c1-3-26-18-9-8-13-6-4-5-7-14(13)19(18)15-11-17-16(10-12(15)2)20(22)25-21(23)24-17/h4-11H,3H2,1-2H3,(H4,22,23,24,25)
InChiKey: DYQBRXOQGFCHCN-UHFFFAOYSA-N

Network

Hover on a compound node to display the structore

Target Layer

Model Organisms

Species	Viewmode
Arabidopsis thaliana
Caenorhabditis elegans
Dictyostelium discoideum
Drosophila melanogaster
Escherichia coli
Homo sapiens
Mus musculus
Oryza sativa
Saccharomyces cerevisiae
Schmidtea mediterranea
Other organisms

TDR Pathogens:

Species	Viewmode
Brugia malayi
Chlamydia trachomatis
Echinococcus granulosus
Entamoeba histolytica
Echinococcus multilocularis
Giardia lamblia
Leishmania major
Loa Loa (eye worm)
Mycobacterium leprae
Mycobacterium tuberculosis
Mycobacterium ulcerans
Onchocerca volvulus
Plasmodium falciparum
Plasmodium vivax
Schistosoma mansoni
Trypanosoma brucei
Trypanosoma cruzi
Toxoplasma gondii
Treponema pallidum
Trichomonas vaginalis
Wolbachia endosymbiont of Brugia malayi

Other Pathogens:

Species	Viewmode
Babesia bovis
Candida albicans
Cryptosporidium hominis
Cryptosporidium parvum
Leishmania braziliensis
Leishmania donovani
Leishmania infantum
Leishmania mexicana
Neospora caninum
Plasmodium berghei
Plasmodium knowlesi
Plasmodium yoelii
Schistosoma japonicum
Trypanosoma brucei gambiense
Trypanosoma congolense
Theileria parva

Compound Layer

This is a work in progress. Come back soon to try this features!

Clustering layers

This is a work in progress. Come back soon to try this features!

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
Staphylococcus aureus	Dihydrofolate reductase	Starlite/ChEMBL	References

Predicted pathogen targets for this compound

By orthology

Species	Potential target	Known druggable target/s	Ortholog Group
Candida albicans	dihydrofolate reductase	Get druggable targets OG5_128410	All targets in OG5_128410
Echinococcus granulosus	dihydrofolate reductase	Get druggable targets OG5_128410	All targets in OG5_128410
Mycobacterium ulcerans	dihydrofolate reductase DfrA	Get druggable targets OG5_128410	All targets in OG5_128410
Candida albicans	dihydrofolate reductase	Get druggable targets OG5_128410	All targets in OG5_128410
Chlamydia trachomatis	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
Candida albicans	hypothetical protein	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
Brugia malayi	dihydrofolate reductase family protein	Get druggable targets OG5_128410	All targets in OG5_128410
Schistosoma mansoni	dihydrofolate reductase	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	Get druggable targets OG5_128410	All targets in OG5_128410
Mycobacterium leprae	DIHYDROFOLATE REDUCTASE DFRA (DHFR) (TETRAHYDROFOLATE DEHYDROGENASE)	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

By sequence similarity to non orthologous known druggable targets

Species	Potential target	Known druggable target	Length	Alignment span	Identity
Toxoplasma gondii	bifunctional dihydrofolate reductase-thymidylate synthase	Dihydrofolate reductase	159 aa	185 aa	25.4 %
Plasmodium falciparum	bifunctional dihydrofolate reductase-thymidylate synthase	dihydrofolate reductase	187 aa	202 aa	29.7 %
Leishmania major	dihydrofolate reductase-thymidylate synthase	Dihydrofolate reductase	159 aa	186 aa	26.9 %
Babesia bovis	dihydrofolate reductase/thymidilate synthase	Dihydrofolate reductase	159 aa	155 aa	36.8 %
Theileria parva	dihydrofolate reductase-thymidylate synthase, putative	Dihydrofolate reductase	159 aa	158 aa	27.2 %
Leishmania mexicana	dihydrofolate reductase-thymidylate synthase	Dihydrofolate reductase	159 aa	186 aa	26.3 %
Onchocerca volvulus	Putative dihydrofolate reductase	Dihydrofolate reductase	159 aa	169 aa	29.6 %
Onchocerca volvulus	Germline survival defective-1 homolog	Dihydrofolate reductase	159 aa	159 aa	27.7 %
Cryptosporidium parvum	dihydrofolate reductase-thymidylate synthase	Dihydrofolate reductase	159 aa	150 aa	35.3 %
Neospora caninum	Bifunctional dihydrofolate reductase-thymidylate synthase, related	Dihydrofolate reductase	159 aa	184 aa	27.7 %
Onchocerca volvulus		Dihydrofolate reductase	159 aa	154 aa	25.3 %
Cryptosporidium hominis	chain A, crystal structure of Dhfr	Dihydrofolate reductase	159 aa	150 aa	33.3 %

Ranking Plot

Putative Targets List

Species	Potential target	Raw	Global	Species
Brugia malayi	latrophilin 2 splice variant baaae	0.0039	0.0507	0.0561
Brugia malayi	Intermediate filament tail domain containing protein	0.0031	0.0323	0.0358
Schistosoma mansoni	acetyl-CoA C-acetyltransferase	0.0023	0.0144	0.0146
Schistosoma mansoni	NADP-specific isocitrate dehydrogenase	0.0018	0.0035	0.0025
Entamoeba histolytica	hypothetical protein	0.0041	0.0551	0.5
Echinococcus multilocularis	bromodomain adjacent to zinc finger domain	0.0036	0.0451	0.0486
Loa Loa (eye worm)	hypothetical protein	0.0031	0.0323	0.0358
Loa Loa (eye worm)	hypothetical protein	0.0057	0.0914	0.1012
Echinococcus granulosus	Basic leucine zipper bZIP transcription	0.0041	0.0551	0.0539
Schistosoma mansoni	lamin	0.0031	0.0323	0.0344
Brugia malayi	MH2 domain containing protein	0.0017	0.0023	0.0026
Schistosoma mansoni	Guanine nucleotide-binding protein G(s) subunit alpha (Adenylate cyclase-stimulating G alpha protein)	0.0045	0.0648	0.0704
Echinococcus multilocularis	mothers against decapentaplegic 5	0.0017	0.0023	0.0012
Brugia malayi	MH2 domain containing protein	0.0017	0.0023	0.0026
Mycobacterium leprae	DIHYDROFOLATE REDUCTASE DFRA (DHFR) (TETRAHYDROFOLATE DEHYDROGENASE)	0.0415	0.9029	0.5
Loa Loa (eye worm)	hypothetical protein	0.0017	0.0013	0.0014
Mycobacterium tuberculosis	Dihydrofolate reductase DfrA (DHFR) (tetrahydrofolate dehydrogenase)	0.0415	0.9029	1
Brugia malayi	calcium-independent alpha-latrotoxin receptor 2, putative	0.0018	0.0034	0.0038
Brugia malayi	Bromodomain containing protein	0.0039	0.0505	0.0559
Loa Loa (eye worm)	transport to inner mitochondrial membrane family member	0.0047	0.0692	0.0767
Schistosoma mansoni	bromodomain containing protein	0.0064	0.1077	0.1181
Echinococcus granulosus	diuretic hormone 44 receptor GPRdih2	0.0018	0.0034	0.0022
Loa Loa (eye worm)	transcription factor SMAD2	0.0257	0.5444	0.6029
Loa Loa (eye worm)	TK/KIN16 protein kinase	0.0018	0.0039	0.0043
Plasmodium vivax	bifunctional dihydrofolate reductase-thymidylate synthase, putative	0.0159	0.3222	1
Echinococcus granulosus	NADP dependent isocitrate dehydrogenase	0.0018	0.0035	0.0022
Loa Loa (eye worm)	isocitrate dehydrogenase	0.0018	0.0035	0.0039
Echinococcus multilocularis	dihydrofolate reductase	0.0415	0.9029	1
Loa Loa (eye worm)	latrophilin receptor protein 2	0.0018	0.0034	0.0038
Echinococcus multilocularis	Basic leucine zipper (bZIP) transcription	0.0041	0.0551	0.0597
Echinococcus granulosus	smad	0.0017	0.0023	0.0011
Plasmodium falciparum	mitochondrial import inner membrane translocase subunit TIM10, putative	0.0047	0.0692	0.2063
Schistosoma mansoni	smad1 5 8 and	0.0017	0.0023	0.0012
Loa Loa (eye worm)	MH1 domain-containing protein	0.0017	0.0023	0.0026
Brugia malayi	intermediate filament protein	0.0031	0.0323	0.0358
Echinococcus granulosus	bromodomain adjacent to zinc finger domain	0.006	0.0995	0.0984
Echinococcus granulosus	guanine nucleotide binding protein Gs subunit	0.0045	0.0648	0.0636
Echinococcus multilocularis	guanine nucleotide binding protein G(s) subunit	0.0045	0.0648	0.0704
Loa Loa (eye worm)	bromodomain containing protein	0.0018	0.0032	0.0035
Echinococcus granulosus	methyl CpG binding domain protein 2	0.0017	0.0018	0.0005
Schistosoma mansoni	hypothetical protein	0.0018	0.0034	0.0024
Toxoplasma gondii	bifunctional dihydrofolate reductase-thymidylate synthase	0.0159	0.3222	1
Schistosoma mansoni	zinc finger protein	0.002	0.0076	0.007
Schistosoma mansoni	transcription factor LCR-F1	0.0041	0.0551	0.0597
Toxoplasma gondii	mitochondrial import inner membrane translocase subunit TIM10, putative	0.0047	0.0692	0.2063
Schistosoma mansoni	smad1 5 8 and	0.0017	0.0023	0.0012
Echinococcus multilocularis	lamin dm0	0.0031	0.0323	0.0344
Brugia malayi	Corticotropin releasing factor receptor 2 precursor, putative	0.0057	0.0914	0.1012
Loa Loa (eye worm)	intermediate filament tail domain-containing protein	0.0031	0.0323	0.0358
Schistosoma mansoni	hypothetical protein	0.0018	0.0034	0.0024
Loa Loa (eye worm)	hypothetical protein	0.0041	0.0561	0.0621
Plasmodium falciparum	bifunctional dihydrofolate reductase-thymidylate synthase	0.0159	0.3222	1
Brugia malayi	PHD-finger family protein	0.0025	0.0198	0.0219
Schistosoma mansoni	mitochondrial import inner membrane translocase subunit tim10	0.0047	0.0692	0.0754
Schistosoma mansoni	Smad4	0.0017	0.0023	0.0012
Schistosoma mansoni	Guanine nucleotide-binding protein G(s) subunit alpha (Adenylate cyclase-stimulating G alpha protein)	0.0045	0.0648	0.0704
Loa Loa (eye worm)	hypothetical protein	0.0017	0.0013	0.0014
Echinococcus multilocularis	cadherin EGF LAG seven pass G type receptor	0.0018	0.0034	0.0024
Echinococcus multilocularis	geminin	0.0385	0.8353	0.925
Schistosoma mansoni	histone-lysine n-methyltransferase setb1	0.0017	0.0018	0.0006
Echinococcus granulosus	TGF beta signal transducer SmadC	0.0017	0.0023	0.0011
Brugia malayi	Isocitrate dehydrogenase	0.0018	0.0035	0.0039
Echinococcus multilocularis	isocitrate dehydrogenase 2 (NADP+)	0.0018	0.0035	0.0025
Brugia malayi	dihydrofolate reductase family protein	0.0415	0.9029	1
Toxoplasma gondii	TIM10 family protein, putative	0.0047	0.0692	0.2063
Loa Loa (eye worm)	hypothetical protein	0.0017	0.0013	0.0014
Schistosoma mansoni	hypothetical protein	0.0021	0.01	0.0097
Echinococcus granulosus	guanine nucleotide binding protein Gs subunit	0.0045	0.0648	0.0636
Echinococcus multilocularis	NADP dependent isocitrate dehydrogenase	0.0018	0.0035	0.0025
Trypanosoma cruzi	dihydrofolate reductase-thymidylate synthase	0.0159	0.3222	1
Echinococcus multilocularis	expressed protein	0.0047	0.0692	0.0754
Echinococcus multilocularis	smad	0.0017	0.0023	0.0012
Echinococcus multilocularis	isocitrate dehydrogenase	0.0018	0.0035	0.0025
Loa Loa (eye worm)	GTP-binding regulatory protein Gs alpha-S chain	0.0045	0.0648	0.0717
Echinococcus granulosus	histone lysine methyltransferase setb	0.0017	0.0018	0.0005
Echinococcus multilocularis	bromodomain adjacent to zinc finger domain	0.006	0.0995	0.109
Echinococcus granulosus	lamin	0.0031	0.0323	0.0311
Echinococcus multilocularis	fetal alzheimer antigen, falz	0.0023	0.0144	0.0146
Loa Loa (eye worm)	hypothetical protein	0.003	0.031	0.0344
Brugia malayi	Smad1	0.0017	0.0023	0.0026
Schistosoma mansoni	methyl-cpg binding protein mbd	0.0017	0.0018	0.0006
Brugia malayi	Latrophilin receptor protein 2	0.0018	0.0034	0.0038
Loa Loa (eye worm)	MH2 domain-containing protein	0.0017	0.0023	0.0026
Echinococcus granulosus	fetal alzheimer antigen falz	0.0023	0.0144	0.0131
Echinococcus multilocularis	GPCR, family 2	0.0018	0.0034	0.0024
Loa Loa (eye worm)	hypothetical protein	0.0172	0.3527	0.3906
Echinococcus multilocularis	TGF beta signal transducer SmadC	0.0017	0.0023	0.0012
Echinococcus granulosus	intermediate filament protein	0.0031	0.0323	0.0311
Brugia malayi	Calcitonin receptor-like protein seb-1	0.0057	0.0914	0.1012
Echinococcus granulosus	lamin dm0	0.0031	0.0323	0.0311
Echinococcus multilocularis	lamin	0.0031	0.0323	0.0344
Brugia malayi	Mitochondrial import inner membrane translocase subunit TIM10	0.0047	0.0692	0.0767
Schistosoma mansoni	hypothetical protein	0.0039	0.0507	0.0548
Loa Loa (eye worm)	PHD-finger family protein	0.0021	0.01	0.0111
Loa Loa (eye worm)	hypothetical protein	0.0039	0.0507	0.0561
Echinococcus granulosus	Smad4	0.0017	0.0023	0.0011
Onchocerca volvulus		0.0172	0.3527	1
Loa Loa (eye worm)	hypothetical protein	0.0043	0.0604	0.0669
Schistosoma mansoni	smad1 5 8 and	0.0017	0.0023	0.0012
Echinococcus granulosus	mothers against decapentaplegic 5	0.0017	0.0023	0.0011
Schistosoma mansoni	hypothetical protein	0.0018	0.0034	0.0024
Brugia malayi	Bromodomain containing protein	0.0076	0.1346	0.149
Echinococcus granulosus	GPCR family 2	0.0018	0.0034	0.0022
Brugia malayi	MH2 domain containing protein	0.0257	0.5444	0.6029
Echinococcus granulosus	dihydrofolate reductase	0.0415	0.9029	0.9028
Loa Loa (eye worm)	hypothetical protein	0.0018	0.0034	0.0038
Brugia malayi	MH1 domain containing protein	0.0017	0.0023	0.0026
Schistosoma mansoni	hypothetical protein	0.0018	0.0034	0.0024
Loa Loa (eye worm)	MH2 domain-containing protein	0.0257	0.5444	0.6029
Echinococcus multilocularis	zinc finger protein	0.002	0.0076	0.007
Loa Loa (eye worm)	pigment dispersing factor receptor c	0.0057	0.0914	0.1012
Echinococcus multilocularis	diuretic hormone 44 receptor GPRdih2	0.0018	0.0034	0.0024
Echinococcus multilocularis	methyl CpG binding domain protein 2	0.0017	0.0018	0.0006
Loa Loa (eye worm)	Smad1	0.0017	0.0023	0.0026
Echinococcus multilocularis	guanine nucleotide binding protein G(s) subunit	0.0045	0.0648	0.0704
Echinococcus granulosus	geminin	0.0385	0.8353	0.8351
Brugia malayi	isocitrate dehydrogenase	0.0018	0.0035	0.0039
Schistosoma mansoni	hypothetical protein	0.0041	0.0551	0.0597
Loa Loa (eye worm)	hypothetical protein	0.0039	0.0506	0.0561
Schistosoma mansoni	hypothetical protein	0.0385	0.8353	0.925
Echinococcus multilocularis	Smad4	0.0017	0.0023	0.0012
Brugia malayi	Immunoglobulin I-set domain containing protein	0.0018	0.0039	0.0043
Brugia malayi	GTP-binding regulatory protein Gs alpha-S chain, putative	0.0045	0.0648	0.0717
Schistosoma mansoni	dihydrofolate reductase	0.0415	0.9029	1
Echinococcus multilocularis	histone lysine methyltransferase setb histone lysine methyltransferase eggless	0.0017	0.0018	0.0006
Brugia malayi	hypothetical protein	0.0172	0.3527	0.3906
Schistosoma mansoni	methyl-cpg binding protein mbd	0.0017	0.0018	0.0006
Plasmodium vivax	mitochondrial import inner membrane translocase subunit TIM10, putative	0.0047	0.0692	0.2063
Brugia malayi	MH1 domain containing protein	0.0017	0.0023	0.0026
Loa Loa (eye worm)	hypothetical protein	0.0072	0.1248	0.1382
Echinococcus granulosus	cadherin EGF LAG seven pass G type receptor	0.0018	0.0034	0.0022
Echinococcus multilocularis	NADP dependent isocitrate dehydrogenase	0.0018	0.0035	0.0025
Entamoeba histolytica	hypothetical protein	0.0041	0.0551	0.5
Echinococcus multilocularis	NADP dependent isocitrate dehydrogenase	0.0018	0.0035	0.0025
Schistosoma mansoni	smad	0.0017	0.0023	0.0012
Trypanosoma brucei	dihydrofolate reductase-thymidylate synthase	0.0159	0.3222	1
Schistosoma mansoni	hypothetical protein	0.0385	0.8353	0.925
Schistosoma mansoni	intermediate filament proteins	0.0031	0.0323	0.0344
Loa Loa (eye worm)	intermediate filament protein	0.0031	0.0323	0.0358
Entamoeba histolytica	hypothetical protein	0.0041	0.0551	0.5
Schistosoma mansoni	histone-lysine n-methyltransferase setb1	0.0017	0.0018	0.0006
Brugia malayi	Dihydrofolate reductase	0.0415	0.9029	1
Loa Loa (eye worm)	dihydrofolate reductase	0.0415	0.9029	1
Schistosoma mansoni	lamin	0.0031	0.0323	0.0344
Echinococcus multilocularis	musashi	0.0031	0.0323	0.0344
Mycobacterium ulcerans	dihydrofolate reductase DfrA	0.0415	0.9029	0.5
Chlamydia trachomatis	dihydrofolate reductase	0.0415	0.9029	0.5
Leishmania major	dihydrofolate reductase-thymidylate synthase	0.0159	0.3222	1
Entamoeba histolytica	hypothetical protein	0.0041	0.0551	0.5
Schistosoma mansoni	TGF-beta signal transducer Smad2	0.0017	0.0023	0.0012
Echinococcus granulosus	expressed protein	0.0047	0.0692	0.0681
Brugia malayi	hypothetical protein	0.0041	0.0551	0.0611
Echinococcus granulosus	bromodomain adjacent to zinc finger domain	0.0036	0.0451	0.0439
Schistosoma mansoni	Guanine nucleotide-binding protein G(s) subunit alpha (Adenylate cyclase-stimulating G alpha protein)	0.0045	0.0648	0.0704
Loa Loa (eye worm)	hypothetical protein	0.0017	0.0018	0.002
Echinococcus granulosus	zinc finger protein	0.002	0.0076	0.0063

Activities

Activity type	Activity value	Assay description	Source	Reference
Ki (binding)	= 0.026 nM	Inhibition of Staphylococcus aureus DHFR assessed as oxidation of NADPH using dihydrofolate as substrate pre-incubated for 10 mins before substrate addition by spectrophotometry	ChEMBL.	21831637
Ki (binding)	= 0.026 nM	BindingDB_Patents: Inhibition Assay. Antibacterial activity as measured by the minimal inhibitory concentrations (MIC) and minimal bactericidal concentrations of compounds are well known (see., e.g., National Committee for Clinical Laboratory Standards 2000 Performance standards for antimicrobial disk susceptibility tests: approved standard, 7th ed. M2-A7, vol. 20, no. 1, Committee for Clinical Laboratory Standards, Wayne, Pa.).	ChEMBL.	No reference
Ki (binding)	= 4.5 nM	Inhibition of human DHFR assessed as oxidation of NADPH using dihydrofolate as substrate pre-incubated for 10 mins before substrate addition by spectrophotometry	ChEMBL.	21831637
Ki (binding)	= 4.5 nM	Inhibition Assay	BINDINGDB.	No reference
MIC (functional)	= 16 ug ml-1	Antibacterial activity against Escherichia coli ATCC 35218 by CLSI microdilution method	ChEMBL.	21831637

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

ChEMBL: CHEMBL1818128

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.

Detailed information for compound 1106587