Detailed information for compound 29461
Basic information
Technical information
- Name: Unnamed compound
- MW: 304.344 | Formula: C15H20N4O3
-
H donors: 2
H acceptors: 2
LogP: 1.71
Rotable bonds: 6
Rule of 5 violations (Lipinski): 1 - SMILES: CCOc1cc(Cc2cnc(nc2N)N)cc(c1OC)OC
- InChi: 1S/C15H20N4O3/c1-4-22-12-7-9(6-11(20-2)13(12)21-3)5-10-8-18-15(17)19-14(10)16/h6-8H,4-5H2,1-3H3,(H4,16,17,18,19)
- InChiKey: MJBWRUCEYONERX-UHFFFAOYSA-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 |
| Lactococcus lactis subsp. lactis (strain IL1403) (Streptococcuslactis) | Dihydrofolate reductase | Starlite/ChEMBL | References |
| Staphylococcus aureus | Dihydrofolate reductase | Starlite/ChEMBL | References |
| Escherichia coli | Dihydrofolate reductase | Starlite/ChEMBL | References |
Predicted pathogen targets for this compound
By orthology
By sequence similarity to non orthologous known druggable targets
Obtained from network model
Ranking Plot
Putative Targets List
| Species | Potential target | Raw | Global | Species |
|---|---|---|---|---|
| Giardia lamblia | Translation initiation factor eIF-4A, putative | 0.0103 | 0 | 0.5 |
| Loa Loa (eye worm) | dihydrofolate reductase | 0.0963 | 1 | 1 |
| Echinococcus granulosus | geminin | 0.0164 | 0.0718 | 0.0718 |
| Plasmodium vivax | bifunctional dihydrofolate reductase-thymidylate synthase, putative | 0.0579 | 0.5546 | 1 |
| Treponema pallidum | ATP-dependent RNA helicase | 0.0103 | 0 | 0.5 |
| Echinococcus granulosus | thymidylate synthase | 0.013 | 0.0316 | 0.0316 |
| Brugia malayi | thymidylate synthase | 0.013 | 0.0316 | 0.0316 |
| Echinococcus multilocularis | thymidylate synthase | 0.013 | 0.0316 | 0.0316 |
| Echinococcus granulosus | dihydrofolate reductase | 0.0963 | 1 | 1 |
| Echinococcus multilocularis | geminin | 0.0164 | 0.0718 | 0.0718 |
| Brugia malayi | Dihydrofolate reductase | 0.0963 | 1 | 1 |
| Schistosoma mansoni | dihydrofolate reductase | 0.0963 | 1 | 1 |
| Mycobacterium tuberculosis | Probable thymidylate synthase ThyA (ts) (TSASE) | 0.013 | 0.0316 | 0.0316 |
| Trypanosoma cruzi | dihydrofolate reductase-thymidylate synthase | 0.0579 | 0.5546 | 1 |
| Schistosoma mansoni | hypothetical protein | 0.0164 | 0.0718 | 0.0718 |
| Leishmania major | dihydrofolate reductase-thymidylate synthase | 0.0579 | 0.5546 | 1 |
| Mycobacterium leprae | DIHYDROFOLATE REDUCTASE DFRA (DHFR) (TETRAHYDROFOLATE DEHYDROGENASE) | 0.0963 | 1 | 1 |
| Plasmodium falciparum | bifunctional dihydrofolate reductase-thymidylate synthase | 0.0579 | 0.5546 | 1 |
| Mycobacterium ulcerans | dihydrofolate reductase DfrA | 0.0963 | 1 | 1 |
| Chlamydia trachomatis | dihydrofolate reductase | 0.0963 | 1 | 0.5 |
| Loa Loa (eye worm) | thymidylate synthase | 0.013 | 0.0316 | 0.0316 |
| Onchocerca volvulus | 0.013 | 0.0316 | 1 | |
| Schistosoma mansoni | bifunctional dihydrofolate reductase-thymidylate synthase | 0.013 | 0.0316 | 0.0316 |
| Echinococcus multilocularis | dihydrofolate reductase | 0.0963 | 1 | 1 |
| Trichomonas vaginalis | DEAD box ATP-dependent RNA helicase, putative | 0.0103 | 0 | 0.5 |
| Trichomonas vaginalis | DEAD box ATP-dependent RNA helicase, putative | 0.0103 | 0 | 0.5 |
| Toxoplasma gondii | bifunctional dihydrofolate reductase-thymidylate synthase | 0.0579 | 0.5546 | 1 |
| Schistosoma mansoni | hypothetical protein | 0.0164 | 0.0718 | 0.0718 |
| Trichomonas vaginalis | DEAD box ATP-dependent RNA helicase, putative | 0.0103 | 0 | 0.5 |
| Mycobacterium tuberculosis | Dihydrofolate reductase DfrA (DHFR) (tetrahydrofolate dehydrogenase) | 0.0963 | 1 | 1 |
| Entamoeba histolytica | DEAD/DEAH box helicase, putative | 0.0103 | 0 | 0.5 |
| Trypanosoma brucei | dihydrofolate reductase-thymidylate synthase | 0.0579 | 0.5546 | 1 |
Activities
| Activity type | Activity value | Assay description | Source | Reference |
|---|---|---|---|---|
| F (ADMET) | = 0.79 | Oral bioavailability in dog | ChEMBL. | 2754716 |
| I50 (binding) | = 0.4 M | In vitro inhibition of E. coli dihydrofolate reductase. | ChEMBL. | 2754716 |
| I50 (binding) | = 17 M | In vitro inhibition of dihydrofolate reductase enzymes in Neisseria gonorrhoeae | ChEMBL. | 2754716 |
| I50 (binding) | = 14000 M | In vitro inhibition of rat liver dihydrofolate reductase. | ChEMBL. | 2754716 |
| I50 (binding) | = 1700000000 M | Inhibition of N. gonorrhoeae Dihydrofolate reductase(DHFR) | ChEMBL. | 3121854 |
| IC50 (binding) | = 0.000000004 M | In vitro inhibition of E. coli dihydrofolate reductase. | ChEMBL. | 2754716 |
| IC50 (binding) | = 0.00000017 M | Inhibition of N. gonorrhoeae Dihydrofolate reductase(DHFR) | ChEMBL. | 3121854 |
| IC50 (binding) | = 0.00000017 M | In vitro inhibition of dihydrofolate reductase enzymes in Neisseria gonorrhoeae | ChEMBL. | 2754716 |
| IC50 (binding) | = 0.00014 M | In vitro inhibition of rat liver dihydrofolate reductase. | ChEMBL. | 2754716 |
| Inhibition (functional) | = -1.63 % | ST_JUDE_LEISH: Cytotoxicity at 2uM final concentration against transgenic Leishmania Mexicana promastigotes LmGLUT1 that are glucose transport deficient and complemented with the human glucose transporter GLUT1. Activity is measured by DNA content using SYBR green in vitro | ChEMBL. | No reference |
| Inhibition (functional) | = -0.5 % | ST_JUDE_LEISH: Cytotoxicity at 2uM final concentration against transgenic Leishmania Mexicana promastigotes LmPfHT that are glucose transport deficient and complemented with the Plasmodium falciparum hexose transporter. Activity is measured by by DNA content using SYBR green in vitro | ChEMBL. | No reference |
| Inhibition (functional) | = -0.04 % | ST_JUDE_LEISH: Cytotoxicity at 2uM final concentration against transgenic Leishmania Mexicana promastigotes LmGT2 that are glucose transport deficient and complemented with the L. Mexicana glucose transporter 2. Activity is measured by by DNA content using SYBR green in vitro | ChEMBL. | No reference |
| Inhibition (functional) | = 0 % | GSK_TCMDC: Inhibition of Plasmodium falciparum Dd2 in whole red blood cells, using parasite LDH activity as an index of growth. Test compounds present at 2uM | ChEMBL. | 20485427 |
| Inhibition (functional) | = 0 % | GSK_TCMDC: Inhibition of Plasmodium falciparum 3D7 LDH activity, using an LDH reporter assay. Test compounds present at 2uM | ChEMBL. | 20485427 |
| Inhibition (functional) | = 0 % | GSK_TCMDC: Percent inhibition of human HepG2 cell line. Test compounds present at 10uM. | ChEMBL. | 20485427 |
| Inhibition (functional) | = 90 % | GSK_TCMDC: Inhibition of Plasmodium falciparum 3D7 in whole red blood cells, using parasite LDH activity as an index of growth. Test compounds present at 2uM | ChEMBL. | 20485427 |
| Inhibition frequency index (IFI) (functional) | = 2.17 | Inhibition Frequency Index (IFI) | GSK. | 20485427 |
| Ki (binding) | = 0.5 nM | Antibacterial activity against Escherichia coli | ChEMBL. | 2754716 |
| Ki (binding) | = 0.5 nM | Antibacterial activity against Escherichia coli | ChEMBL. | 2754716 |
| Ki (binding) | = 2.5 nM | Antibacterial activity against Staphylococcus aureus | ChEMBL. | 2754716 |
| Ki (binding) | = 2.5 nM | Antibacterial activity against Staphylococcus aureus | ChEMBL. | 2754716 |
| MIC (functional) | = 0.3 ug ml-1 | Antibacterial (Staphylococcus pyogenes CN10) activity compared to trimethoprim. | ChEMBL. | 2754716 |
| MIC (functional) | = 0.3 ug ml-1 | Antibacterial (Staphylococcus aureus CN491) activity compared to trimethoprim. | ChEMBL. | 2754716 |
| MIC (functional) | = 1 ug ml-1 | Antibacterial (Pasteurella multocides ATCC6587) activity compared to trimethoprim. | ChEMBL. | 2754716 |
| MIC (functional) | = 1 ug ml-1 | Antibacterial (Mycobacterium smegmatis S3254) activity compared to trimethoprim. | ChEMBL. | 2754716 |
| MIC (functional) | = 1 ug ml-1 | Antibacterial (Salmonella typhi CN512) activity compared to trimethoprim. | ChEMBL. | 2754716 |
| MIC (functional) | = 1 ug ml-1 | Antibacterial (Shigella flexneri CN6007) activity compared to trimethoprim. | ChEMBL. | 2754716 |
| MIC (functional) | = 1 ug ml-1 | Antibacterial (Klebsiella pneumoniae CN3632) activity compared to trimethoprim. | ChEMBL. | 2754716 |
| MIC (functional) | = 1 ug ml-1 | Antibacterial (Enterbacter aerogenes 2201/86) activity compared to trimethoprim. | ChEMBL. | 2754716 |
| MIC (functional) | = 1 ug ml-1 | Antibacterial (Proteus vulgaris CN329) activitiy compared to trimethoprim. | ChEMBL. | 2754716 |
| MIC (functional) | = 2.6 ug ml-1 | Antibacterial (Escherichia coli) activity compared to trimethoprim. | ChEMBL. | 2754716 |
| MIC (functional) | = 2.6 ug ml-1 | Antibacterial (Escherichia coli) activity compared to trimethoprim. | ChEMBL. | 2754716 |
| MIC (functional) | = 3 ug ml-1 | Antibacterial (Serratia marcescens CN2398) activity compared to trimethoprim. | ChEMBL. | 2754716 |
| MIC (functional) | = 180 uM | Inhibition of growth of Neisseria gonorrhoeae | ChEMBL. | 3121854 |
| Percent growth inhibition (functional) | = -3 % | Percent inhibition of HepG2 growth (at 10 uM) | GSK. | 20485427 |
| Percent growth inhibition (functional) | = -1 % | Percent inhibition of P. falciparum lactate dehydrogenase activity (at 2 uM) | GSK. | 20485427 |
| Percent growth inhibition (functional) | = 0 % | Percent inhibition of P. falciparum Dd2 growth (at 2 uM) | GSK. | 20485427 |
| Percent growth inhibition (functional) | = 90 % | Percent inhibition of P. falciparum 3D7 growth (at 2 uM) | GSK. | 20485427 |
| T1/2 (ADMET) | = 3.13 hr | Half-life of the compound in dogs Plasma | ChEMBL. | 2754716 |
| XC50 (functional) | = 6.04 | XC50 determination of P. falciparum 3D7 growth | GSK. | 20485427 |
| XC50 (functional) | = 0.91316 uM | GSK_TCMDC: Inhibition of Plasmodium falciparum 3D7 in whole erythrocytes, using parasite LDH activity as an index of growth. | ChEMBL. | 20485427 |
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.
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: CHEMBL23609
- Search by GSK
Bibliographic References
3 literature references were collected for this gene.
If you have references for this compound, please enter them in a user comment (below) or Contact us.