Detailed information for compound 42285

Basic information

Technical information
  • TDR Targets ID: 42285
  • Name: 2-[[4-[3-(2,6-diamino-4-oxo-1H-pyrimidin-5-yl )propylamino]benzoyl]amino]pentanedioic acid
  • MW: 432.43 | Formula: C19H24N6O6
  • H donors: 7 H acceptors: 8 LogP: 0.54 Rotable bonds: 12
    Rule of 5 violations (Lipinski): 2
  • SMILES: OC(=O)CCC(C(=O)O)NC(=O)c1ccc(cc1)NCCCc1c(N)nc(nc1O)N
  • InChi: 1S/C19H24N6O6/c20-15-12(17(29)25-19(21)24-15)2-1-9-22-11-5-3-10(4-6-11)16(28)23-13(18(30)31)7-8-14(26)27/h3-6,13,22H,1-2,7-9H2,(H,23,28)(H,26,27)(H,30,31)(H5,20,21,24,25,29)
  • InChiKey: CPVRCGLCOADOPV-UHFFFAOYSA-N  


Substructure search Similarity search

Network

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Synonyms

  • 2-[[[4-[3-(2,6-diamino-4-oxo-1H-pyrimidin-5-yl)propylamino]phenyl]-oxomethyl]amino]pentanedioic acid
  • 2-[[4-[3-[2,6-bis(azanyl)-4-oxo-1H-pyrimidin-5-yl]propylamino]phenyl]carbonylamino]pentanedioic acid
  • 2-[[4-[3-(2,6-diamino-4-keto-1H-pyrimidin-5-yl)propylamino]benzoyl]amino]glutaric acid
  • N-(4-((3-(2,4-diamino-1,6-dihydro-6-oxo-5-pyrimidinyl)propyl)amino)benzoyl)glutamic acid
  • 2-[[4-[3-(2,4-diamino-6-oxo-3H-pyrimidin-5-yl)propylamino]benzoyl]amino]pentanedioic acid
  • 2-[[[4-[3-(2,4-diamino-6-oxo-3H-pyrimidin-5-yl)propylamino]phenyl]-oxomethyl]amino]pentanedioic acid
  • 2-[[4-[3-(2,4-diamino-6-keto-3H-pyrimidin-5-yl)propylamino]benzoyl]amino]glutaric acid
  • 2-[[4-[3-(2,4-diamino-6-oxo-3H-pyrimidin-5-yl)propylamino]phenyl]carbonylamino]pentanedioic acid

Targets

Known targets for this compound

No curated genes were found associated with this compound

Predicted pathogen targets for this compound

By orthology
No druggable targets predicted by orthology data
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
Wolbachia endosymbiont of Brugia malayi phosphoribosylamine--glycine ligase 0.018 0.0718 0.2563
Loa Loa (eye worm) hypothetical protein 0.0133 0.0491 0.5
Schistosoma mansoni family S9 non-peptidase homologue (S09 family) 0.0133 0.0491 0.0281
Mycobacterium leprae PROBABLE PHOSPHORIBOSYLAMINE--GLYCINE LIGASE PURD (GARS) (GLYCINAMIDE RIBONUCLEOTIDE SYNTHETASE) (PHOSPHORIBOSYLGLYCINAMIDE SYNT 0.018 0.0718 0.2563
Brugia malayi Carboxylesterase family protein 0.0133 0.0491 0.5
Loa Loa (eye worm) hypothetical protein 0.0133 0.0491 0.5
Echinococcus multilocularis microsomal glutathione S transferase 3 0.048 0.2174 1
Plasmodium falciparum carbamoyl phosphate synthetase 0.0076 0.0216 0.5
Mycobacterium tuberculosis Probable bifunctional purine biosynthesis protein PurH: phosphoribosylaminoimidazolecarboxamide formyltransferase (AICAR transfo 0.0586 0.2686 1
Mycobacterium ulcerans bifunctional phosphoribosylaminoimidazolecarboxamide formyltransferase/IMP cyclohydrolase 0.0586 0.2686 1
Toxoplasma gondii MAPEG family protein 0.048 0.2174 1
Loa Loa (eye worm) acetylcholinesterase 1 0.0133 0.0491 0.5
Mycobacterium leprae Probable bifunctional purine biosynthesis protein PurH : phosphoribosylaminoimidazolecarboxamide formyltransferase (aicar transf 0.0586 0.2686 1
Wolbachia endosymbiont of Brugia malayi AICAR transformylase/IMP cyclohydrolase PurH 0.0586 0.2686 1
Onchocerca volvulus 0.004 0.0039 1
Plasmodium vivax carbamoyl phosphate synthetase, putative 0.0076 0.0216 0.5
Wolbachia endosymbiont of Brugia malayi carbamoyl phosphate synthase large subunit 0.0076 0.0216 0.0669
Brugia malayi Carboxylesterase family protein 0.0133 0.0491 0.5
Echinococcus granulosus microsomal glutathione S transferase 3 0.048 0.2174 1
Schistosoma mansoni microsomal glutathione s-transferase 0.048 0.2174 0.2001
Mycobacterium ulcerans phosphoribosylamine--glycine ligase 0.018 0.0718 0.2563
Loa Loa (eye worm) carboxylesterase 0.0133 0.0491 0.5
Leishmania major carbamoyl-phosphate synthase, putative 0.0076 0.0216 0.5
Mycobacterium ulcerans carbamoyl phosphate synthase large subunit 0.0076 0.0216 0.0669

Activities

Activity type Activity value Assay description Source Reference
Activity (binding) 0 Inhibitory activity against 5,10-methylenetetrahydrofolate dehydrogenase from Escherichia coli at a concentration of 0.1 mM; NT=Not tested ChEMBL. 2299624
ED50 (functional) = 0.037 uM Effective dose which is required to inhibit 50% of the cell growth of MCF-7 cells in culture. ChEMBL. 1995883
I50 (binding) = 3 uM Inhibition of GAR transformylase in hog liver ChEMBL. 1995883
I50 (binding) = 94 uM Inhibition of 5-aminoimidazole-4-carboxamide AICAR formyltransferase in MOLT-4 cells ChEMBL. 1995883
I50 (binding) > 100 uM Inhibition of thymidylate synthase (TS) in human ChEMBL. 1995883
I50 (binding) > 100 uM Inhibition of dihydrofolate reductase (DHFR) in WIL2 cells ChEMBL. 1995883
IC50 (functional) = 37 nM Antitumor activity on MCF-7 breast adenocarcinoma cell lines ChEMBL. 2299624
IC50 (functional) = 43 nM Antitumor activity on A-427 lung carcinoma cell lines ChEMBL. 2299624
IC50 (functional) = 45 nM Antitumor activity on WiDr colon adenocarcinoma cell lines ChEMBL. 2299624
IC50 (functional) = 47 nM Antitumor activity on CCRF-CEM T-cell acute lymphoblastic leukemia cell lines ChEMBL. 2299624
IC50 (functional) = 50 nM Antitumor activity on SW 480 colon adenocarcinoma cell lines ChEMBL. 2299624
IC50 (functional) = 58 nM Antitumor activity on MOLT-4 T-cell acute lymphoblastic leukemia cell lines ChEMBL. 2299624
IC50 (binding) 0 uM Diglutamyl homologue inhibition activity against the Glycinamide ribonucleotide transformylase(GAR-TFase)was determined against hog liver; NT=Not tested ChEMBL. 2299624
IC50 (binding) 0 uM Diglutamyl homologue inhibition activity against the AICAR formyltransferase was determined against MOLT-4; NT=Not tested ChEMBL. 2299624
IC50 (binding) 0 uM Triglutamyl homologue inhibition activity against Glycinamide ribonucleotide transformylase(GAR-TFase)was determined against hog liver; NT=Not tested ChEMBL. 2299624
IC50 (functional) = 0.037 uM Compound was evaluated in vitro for inhibition of growth of MCF-7 human breast adenocarcinoma using 72 hours continuous exposure ChEMBL. 1573633
IC50 (binding) = 0.08 uM Hexaglutamyl homologue inhibition activity against the Glycinamide ribonucleotide transformylase(GAR-TFase) was determined against L cell ChEMBL. 2299624
IC50 (functional) = 0.088 uM Evaluated in vitro for ability to inhibit the L cell lines. ChEMBL. 2299624
IC50 (functional) = 0.11 uM Evaluated in vitro for ability to inhibit the Detroit 98 cell lines ChEMBL. 2299624
IC50 (binding) = 0.26 uM Hexaglutamyl homologue inhibition activity against the Glycinamide ribonucleotide transformylase(GAR-TFase) was determined against hog liver ChEMBL. 2299624
IC50 (binding) = 0.34 uM Triglutamyl homologue inhibition activity against Glycinamide ribonucleotide transformylase(GAR-TFase)was determined against L cell ChEMBL. 2299624
IC50 (binding) = 0.4 uM Diglutamyl homologue inhibition activity against the Glycinamide ribonucleotide transformylase(GAR-TFase)was determined against L cell ChEMBL. 2299624
IC50 (binding) = 0.7 uM Hexaglutamyl homologue inhibition activity against the AICAR formyltransferase was determined against L cell ChEMBL. 2299624
IC50 (binding) = 0.7 uM Hexaglutamyl homologue inhibition activity against the AICAR formyltransferase was determined against MOLT-4 ChEMBL. 2299624
IC50 (functional) = 1.2 uM Compound was evaluated for inhibition of [3H]-methotrexate uptake into MOLT-4 cells ChEMBL. 1573633
IC50 (binding) = 1.9 uM Triglutamyl homologue inhibition activity against AICAR formyltransferase was determined against L cell ChEMBL. 2299624
IC50 (binding) = 2.6 uM Inhibition activity against Glycinamide ribotide formyltransferase against L cell ChEMBL. 2299624
IC50 (binding) = 3 uM Inhibition activity against Glycinamide ribonucleotide transformylase(GAR-TFase) against L cell ChEMBL. 2299624
IC50 (binding) = 3 uM In vitro inhibition of hog liver GAR transformylase with (6R)-10-formyl-FH4 as cofactor ChEMBL. 1573633
IC50 (binding) = 9.4 uM Diglutamyl homologue inhibition activity against the AICAR formyltransferase was determined against L cell ChEMBL. 2299624
IC50 (binding) = 94 uM Inhibition activity against AICAR formyltransferase determined against MOLT-4 ChEMBL. 2299624
IC50 (binding) = 94 uM In vitro inhibitory activity of the compound against MOLT-4 T-cell leukemia cell AICAR transformylase ChEMBL. 1573633
IC50 (binding) = 200 uM Inhibition activity against AICAR formyltransferase determined against L cell ChEMBL. 2299624
ILS (functional) = 0 % Effect on P388 tumor cell growth in mice. The percentage of increased life span was determined administered 75 mg/kg schedule - QD,days1,5,9 ChEMBL. 2299624
ILS (functional) = 22 % Effect on P388 tumor cell growth in mice. The percentage of increased life span was determined administered 5 mg/kg schedule - t.i.d., days 1-4 ChEMBL. 2299624
ILS (functional) = 40 % Effect on P388 tumor cell growth in mice. The percentage of increased life span was determined administered 7.5 mg/kg schedule - b.i.d., days 1-3 ChEMBL. 2299624
ILS (functional) = 80 % Effect on P388 tumor cell growth in mice. The percentage of increased life span was determined administered 10 mg/kg schedule - t.i.d., days 1-4 ChEMBL. 2299624
Inhibition (functional) = 0 % Evaluated for reversal of L cell inhibition , where reversal of toxicity was evaluated by the addition of Hypoxanthine (37 uM) ChEMBL. 2299624
Inhibition (functional) = 0 % Evaluated for reversal of L cell inhibition , where reversal of toxicity was evaluated by the addition of Thymidine Hypoxanthine ChEMBL. 2299624
Inhibition (binding) = 0 % Evaluated for inhibitory activity on Dihydrofolate reductase(rat liver) at folate substrate concentration of 45 uM ChEMBL. 2299624
Inhibition (binding) = 0 % Evaluated for inhibitory activity on Thymidylate synthase(calf thymus) at folate substrate concentration of 200 uM ChEMBL. 2299624
Inhibition (binding) = 0 % Evaluated for inhibitory activity on 10-formyltetrahydrofolate syhthetase(L cell) at folate substrate concentration of 100 uM ChEMBL. 2299624
Inhibition (binding) = 0 % Evaluated for inhibitory activitie on 5,10-methylenetetrahydrofolate dehydrogenase(L cell) at folate substrate concentration of 100 uM ChEMBL. 2299624
Inhibition (binding) = 0 % Evaluated for inhibitory activitie on Methionine synthase(L cell) at folate substrate concentration of 100 uM ChEMBL. 2299624
Inhibition (binding) = 5 % Evaluated for inhibitory activitie on 5,10-Methenyl Tetrahydrofolate Cyclohydrolase(L cell) at folate substrate concentration of 100 uM ChEMBL. 2299624
Inhibition (functional) = 6 % Evaluated for reversal of L cell inhibition , where reversal of toxicity was evaluated by the addition of Leucovorin (0.2 uM) ChEMBL. 2299624
Inhibition (binding) = 7 % Evaluated for inhibitory activitie on Serine hydroxymethyl transferase(Lcell) at folate substrate concentration of 160 uM ChEMBL. 2299624
Inhibition (functional) = 59 % Evaluated for reversal of L cell inhibition , where reversal of toxicity was evaluated by the addition of Thymidine (20 uM) ChEMBL. 2299624
Ki (functional) = 1 uM Inhibition of the uptake of [3H]-MTX influx into MOLT-4 cells. ChEMBL. 1995883
Km (binding) = 7.3 uM Km value of Hog folylpolyglutamate synthase in presence of the compound relative to aminopterin ChEMBL. 1573633
Km app (binding) = 6.7 uM Apparent Km in microM for its activation for Hog Liver Folyl-polyglutamate synthase was determined ChEMBL. 2299624
Km app (ADMET) = 6.7 uM Compound was evaluated for the substrate activity for hog liver Folyl-polyglutamate synthase ChEMBL. 1995883
Ratio (binding) = 14.9 Ratio of app Km to ral Vmax ChEMBL. 2299624
Ratio (ADMET) = 14.9 Ratio of relative Vmax values to that of apparent Km values. ChEMBL. 1995883
Relative Vmax (ADMET) = 100 Maximum drug concentration (Vmax), relative to a control of 50 uM aminopterin included in each experiment. ChEMBL. 1995883
Relative Vmax (binding) = 100 % Relative Vmax for its activation for Hog Liver Folyl-polyglutamate synthase was determined ChEMBL. 2299624
Vmax (binding) = 106 % Percent Vmax of Hog folylpolyglutamate synthase in presence of the compound relative to aminopterin ChEMBL. 1573633

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.
 
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External resources for this compound

Bibliographic References

3 literature references were collected for this gene.

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