Detailed information for compound 329752
Basic information
Technical information
- Name: Unnamed compound
- MW: 455.464 | Formula: C22H25N5O6
-
H donors: 6
H acceptors: 6
LogP: 1.15
Rotable bonds: 12
Rule of 5 violations (Lipinski): 2 - SMILES: OC(=O)CC[C@@H](C(=O)O)NC(=O)c1ccc(cc1)CCCCc1[nH]c2c(c1)c(=O)[nH]c(n2)N
- InChi: 1S/C22H25N5O6/c23-22-26-18-15(20(31)27-22)11-14(24-18)4-2-1-3-12-5-7-13(8-6-12)19(30)25-16(21(32)33)9-10-17(28)29/h5-8,11,16H,1-4,9-10H2,(H,25,30)(H,28,29)(H,32,33)(H4,23,24,26,27,31)/t16-/m0/s1
- InChiKey: CEPQCJFDTGQKDN-INIZCTEOSA-N
Network
Hover on a compound node to display the structore
Synonyms
No synonyms found for this compound
Targets
Known targets for this compound
| Species | Target name | Source | Bibliographic reference |
|---|---|---|---|
| Homo sapiens | thymidylate synthetase | Starlite/ChEMBL | References |
| Mus musculus | phosphoribosylglycinamide formyltransferase | Starlite/ChEMBL | References |
| Homo sapiens | phosphoribosylglycinamide formyltransferase, phosphoribosylglycinamide synthetase, phosphoribosylaminoimidazole synthetase | Starlite/ChEMBL | References |
Predicted pathogen targets for this compound
By orthology
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 |
|---|---|---|---|---|
| Leishmania major | dihydrofolate reductase-thymidylate synthase | 0.0195 | 0.4436 | 0.5 |
| Loa Loa (eye worm) | thymidylate synthase | 0.0195 | 0.4436 | 0.5 |
| Mycobacterium tuberculosis | Hypothetical protein | 0.0093 | 0.0992 | 0.1149 |
| Trypanosoma brucei | dihydrofolate reductase-thymidylate synthase | 0.0195 | 0.4436 | 0.5 |
| Schistosoma mansoni | bifunctional dihydrofolate reductase-thymidylate synthase | 0.0195 | 0.4436 | 0.5 |
| Echinococcus granulosus | thymidylate synthase | 0.0195 | 0.4436 | 0.5 |
| Plasmodium vivax | bifunctional dihydrofolate reductase-thymidylate synthase, putative | 0.0195 | 0.4436 | 0.5 |
| Trypanosoma cruzi | dihydrofolate reductase-thymidylate synthase | 0.0195 | 0.4436 | 1 |
| Mycobacterium leprae | PROBABLE THYMIDYLATE SYNTHASE THYA (TS) (TSASE) | 0.0195 | 0.4436 | 0.4115 |
| Echinococcus multilocularis | thymidylate synthase | 0.0195 | 0.4436 | 0.5 |
| Trichomonas vaginalis | conserved hypothetical protein | 0.0093 | 0.0992 | 0.5 |
| Mycobacterium tuberculosis | Probable thymidylate synthase ThyA (ts) (TSASE) | 0.0195 | 0.4436 | 1 |
| Mycobacterium ulcerans | thymidylate synthase | 0.0195 | 0.4436 | 0.4115 |
| Toxoplasma gondii | bifunctional dihydrofolate reductase-thymidylate synthase | 0.0195 | 0.4436 | 0.5 |
| Plasmodium falciparum | bifunctional dihydrofolate reductase-thymidylate synthase | 0.0195 | 0.4436 | 0.5 |
| Mycobacterium ulcerans | phosphoribosylamine--glycine ligase | 0.0359 | 1 | 1 |
| Brugia malayi | thymidylate synthase | 0.0195 | 0.4436 | 1 |
| Onchocerca volvulus | 0.0079 | 0.0545 | 0.1228 | |
| Onchocerca volvulus | 0.0195 | 0.4436 | 1 | |
| Wolbachia endosymbiont of Brugia malayi | phosphoribosylamine--glycine ligase | 0.0359 | 1 | 1 |
Activities
| Activity type | Activity value | Assay description | Source | Reference |
|---|---|---|---|---|
| Activity (binding) | Displacement of [3H]folic acid from human FRalpha expressed in chinese hamster RT16 cells after 15 mins by scintillation counting analysis | ChEMBL. | 24256410 | |
| Activity (binding) | Displacement of [3H]folic acid from human FRalpha in Chinese hamster RT16 cells | ChEMBL. | 18680275 | |
| Activity (binding) | Displacement of [3H]folic acid from human FRbeta in Chinese hamster D4 cells | ChEMBL. | 18680275 | |
| Activity (functional) | = 35 % | Induction of apoptosis in human KB cells assessed as viable cells at 1 uM after 96 hrs by Annexin V-FITC/7-AAD staining-based flow cytometry (RVB = 89.6%) | ChEMBL. | 24256410 |
| EC50 (functional) | = 1100 nM | Growth inhibitory activity of the compound against CCRF-CEM human lymphoblastic leukemia cells | ChEMBL. | 16078850 |
| EC50 (functional) | = 1100 nM | Growth inhibitory activity of the compound against CCRF-CEM human lymphoblastic leukemia cells | ChEMBL. | 16078850 |
| EC50 (functional) | = 3050 nM | Growth inhibitory activity of the compound against MTX resistant subline of CCRF-CEM human lymphoblastic leukemia cells | ChEMBL. | 16078850 |
| EC50 (functional) | = 3050 nM | Growth inhibitory activity of the compound against MTX resistant subline of CCRF-CEM human lymphoblastic leukemia cells | ChEMBL. | 16078850 |
| EC50 (functional) | = 8100 nM | Growth inhibitory activity of the compound against resistant CCRF-CEM human lymphoblastic leukemia cells with decreased uptake of MTX | ChEMBL. | 16078850 |
| EC50 (functional) | = 8100 nM | Growth inhibitory activity of the compound against resistant CCRF-CEM human lymphoblastic leukemia cells with decreased uptake of MTX | ChEMBL. | 16078850 |
| EC50 (functional) | = 18000 nM | Growth inhibitory activity of the compound against MTX resistant CCRF-CEM human lymphoblastic leukemia cells with decreased polyglutamylation | ChEMBL. | 16078850 |
| EC50 (functional) | = 18000 nM | Growth inhibitory activity of the compound against MTX resistant CCRF-CEM human lymphoblastic leukemia cells with decreased polyglutamylation | ChEMBL. | 16078850 |
| GI50 (functional) | = 0.000000398 M | Cytotoxicity of compound aganist K-564 leukemia cell line | ChEMBL. | 16078850 |
| GI50 (functional) | = 0.000000398 M | Cytotoxicity of compound aganist K-564 leukemia cell line | ChEMBL. | 16078850 |
| GI50 (functional) | = 0.000000609 M | Cytotoxicity of compound aganist SR leukemia cell line | ChEMBL. | 16078850 |
| GI50 (functional) | = 0.000000609 M | Cytotoxicity of compound aganist SR leukemia cell line | ChEMBL. | 16078850 |
| GI50 (functional) | = 0.000000898 M | Cytotoxicity of compound aganist 786-0 renal cancer cell line | ChEMBL. | 16078850 |
| GI50 (functional) | = 0.000000898 M | Cytotoxicity of compound aganist 786-0 renal cancer cell line | ChEMBL. | 16078850 |
| GI50 (functional) | = 0.00000381 M | Cytotoxicity of compound aganist SW-620 colon cancer cell line | ChEMBL. | 16078850 |
| GI50 (functional) | = 0.00000381 M | Cytotoxicity of compound aganist SW-620 colon cancer cell line | ChEMBL. | 16078850 |
| GI50 (functional) | = 0.00000656 M | Cytotoxicity of compound aganist HL-60 leukemia cell line | ChEMBL. | 16078850 |
| GI50 (functional) | = 0.00000656 M | Cytotoxicity of compound aganist HL-60 leukemia cell line | ChEMBL. | 16078850 |
| IC50 (functional) | = 1.9 nM | Antiproliferative activity against human RFC and FRalpha expressing human KB cells | ChEMBL. | 18680275 |
| IC50 (functional) | = 1.9 nM | Growth inhibition of human KB cells expressing RFC, FRalpha and PCFT after 96 hrs | ChEMBL. | 20085328 |
| IC50 (functional) | = 3.6 nM | Antiproliferative activity against human RFC and FRalpha expressing human IGROV1 cells | ChEMBL. | 18680275 |
| IC50 (functional) | = 3.6 nM | Growth inhibition of human IGROV1 cells expressing RFC, FRalpha and PCFT after 96 hrs | ChEMBL. | 20085328 |
| IC50 (binding) | = 6.8 nM | Inhibition of GARFTase in human KB cells assessed as inhibition of [14C]glycine incorporation into [14C]formylGAR in presence of azaserine | ChEMBL. | 18680275 |
| IC50 (functional) | = 213 nM | Growth inhibition of Chinese hamster R2 cells expressing human PCFT4 after 96 hrs by CellTiter-blue assay | ChEMBL. | 24111942 |
| IC50 (functional) | = 213 nM | Cytotoxicity against chinese hamster R2 cells expressing human PCFT4 after 96 hrs by CellTitre-Blue fluorescence assay | ChEMBL. | 24256410 |
| IC50 (functional) | > 1000 nM | Antiproliferative activity against human RFC expressing Chinese hamster R2 cells | ChEMBL. | 18680275 |
| IC50 (functional) | > 1000 nM | Antiproliferative activity against human RFC and FRalpha expressing human KB cells in presence of folic acid | ChEMBL. | 18680275 |
| IC50 (functional) | > 1000 nM | Antiproliferative activity against human RFC and FRalpha expressing human IGROV1 cells in presence of folic acid | ChEMBL. | 18680275 |
| IC50 (binding) | = 0.15 uM | Inhibition of mouse recombinant GARFTase | ChEMBL. | 18680275 |
| IC50 (binding) | = 6.8 uM | Inhibition of GARFtase in human KB cells assessed as [14C]glycine incorporation in to [14C]FGAR in folate free RPMI medium with 2 nM LCV by in-situassay | ChEMBL. | 20085328 |
| IC50 (binding) | > 17 uM | Inhibition of human thymidylate synthetase at 37 degree C pH 7.4 | ChEMBL. | 16078850 |
| IC50 (binding) | > 17 uM | Inhibition of human thymidylate synthetase at 37 degree C pH 7.4 | ChEMBL. | 16078850 |
| IC50 (binding) | > 20 uM | Inhibition of human dihydrofolate reductase at 37 degree C pH 7.4 | ChEMBL. | 16078850 |
| IC50 (binding) | > 20 uM | Inhibition of human dihydrofolate reductase at 37 degree C pH 7.4 | ChEMBL. | 16078850 |
| IC50 (binding) | = 100 uM | Inhibition of Escherichia coli dihydrofolate reductase at 37 degree C pH 7.4 | ChEMBL. | 16078850 |
| IC50 (binding) | > 100 uM | Inhibition of Lactobacillus casei thymidylate synthetase at 37 degree C pH 7.4 | ChEMBL. | 16078850 |
| IC50 (binding) | = 100 uM | Inhibition of Escherichia coli dihydrofolate reductase at 37 degree C pH 7.4 | ChEMBL. | 16078850 |
| IC50 (binding) | > 100 uM | Inhibition of Lactobacillus casei thymidylate synthetase at 37 degree C pH 7.4 | ChEMBL. | 16078850 |
| IC50 (binding) | > 110 uM | Inhibition of Lactobacillus casei dihydrofolate reductase at 37 degree C pH 7.4 | ChEMBL. | 16078850 |
| IC50 (binding) | > 110 uM | Inhibition of Lactobacillus casei dihydrofolate reductase at 37 degree C pH 7.4 | ChEMBL. | 16078850 |
| IC50 (binding) | = 150 uM | Inhibition of mouse recombinant GARFtase assessed as FGAR formation by spectrophotometry | ChEMBL. | 20085328 |
| IC50 (binding) | > 170 uM | Inhibition of Escherichia coli thymidylate synthetase at 37 degree C pH 7.4 | ChEMBL. | 16078850 |
| IC50 (binding) | > 170 uM | Inhibition of Escherichia coli thymidylate synthetase at 37 degree C pH 7.4 | ChEMBL. | 16078850 |
| Inhibition (binding) | < 20 % | Inhibition of human RFC-mediated [3H]MTX transport expressed in Chinese hamster PC43-10 cells | ChEMBL. | 18680275 |
| Inhibition (binding) | < 25 % | Inhibition of human RFC expressed in chinese hamster PC43-10 cells assessed as reduction of [3H]MTX uptake at 10 uM after 48 hrs by scintillation counting analysis relative to control | ChEMBL. | 24256410 |
| Inhibition (functional) | > 97 % | Inhibition of colony formation in human KB cells at 1 uM | ChEMBL. | 18680275 |
| Km (ADMET) | = 6.3 | Km of the compound (FPGS substrate activity) for recombinant human FPGS | ChEMBL. | 16078850 |
| Ratio (ADMET) | = 0.086 | Ratio of Vmax, rel to Km of the compound (FPGS substrate activity) for recombinant human FPGS | ChEMBL. | 16078850 |
| Relative growth (functional) | = 18 % | Protection of CCRF-CEM human leukemia cells against the growth inhibitory effect of MTX by 5 uM of thymidine at 5000 nM concentration of compound | ChEMBL. | 16078850 |
| Relative growth (functional) | = 18 % | Protection of CCRF-CEM human leukemia cells against the growth inhibitory effect of MTX by 5 uM of thymidine at 5000 nM concentration of compound | ChEMBL. | 16078850 |
| Relative growth (functional) | = 85 % | Protection of CCRF-CEM human leukemia cells against the growth inhibitory effect of MTX by 10 uM of hypoxanthine at 5000 nM concentration of compound | ChEMBL. | 16078850 |
| Relative growth (functional) | = 85 % | Protection of CCRF-CEM human leukemia cells against the growth inhibitory effect of MTX by 10 uM of hypoxanthine and 5 uM of thymidine at 5000 nM concentration of compound | ChEMBL. | 16078850 |
| Relative growth (functional) | = 85 % | Protection of CCRF-CEM human leukemia cells against the growth inhibitory effect of MTX by 10 uM of hypoxanthine at 5000 nM concentration of compound | ChEMBL. | 16078850 |
| Relative growth (functional) | = 85 % | Protection of CCRF-CEM human leukemia cells against the growth inhibitory effect of MTX by 10 uM of hypoxanthine and 5 uM of thymidine at 5000 nM concentration of compound | ChEMBL. | 16078850 |
| Vmax rel (ADMET) | = 0.54 | Vmax, rel of the compound (FPGS substrate activity) for recombinant human FPGS | ChEMBL. | 16078850 |
Phenotypes
Whole-cell/tissue/organism interactions
| Species name | Source | Reference | Is orphan |
|---|---|---|---|
| Homo sapiens | ChEMBL23 | 16078850 |
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: CHEMBL365307
Bibliographic References
4 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.