Detailed information for compound 68877

Basic information

Technical information
  • TDR Targets ID: 68877
  • Name: 2-(phosphonomethyl)pentanedioic acid
  • MW: 226.121 | Formula: C6H11O7P
  • H donors: 4 H acceptors: 7 LogP: -2.21 Rotable bonds: 6
    Rule of 5 violations (Lipinski): 1
  • SMILES: OC(=O)CCC(C(=O)O)CP(=O)(O)O
  • InChi: 1S/C6H11O7P/c7-5(8)2-1-4(6(9)10)3-14(11,12)13/h4H,1-3H2,(H,7,8)(H,9,10)(H2,11,12,13)
  • InChiKey: ISEYJGQFXSTPMQ-UHFFFAOYSA-N  


Substructure search Similarity search

Network

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Synonyms

  • 2-(phosphonomethyl)glutaric acid

Targets

Known targets for this compound

Species Target name Source Bibliographic reference
Rattus norvegicus Glutamate carboxypeptidase II Starlite/ChEMBL References
Homo sapiens N-acetylated alpha-linked acidic dipeptidase 2 Starlite/ChEMBL References
Homo sapiens folate hydrolase (prostate-specific membrane antigen) 1 Starlite/ChEMBL References

Predicted pathogen targets for this compound

By orthology
Species Potential target Known druggable target/s Ortholog Group
Schistosoma mansoni NAALADASE L peptidase (M28 family) Get druggable targets OG5_128101 All targets in OG5_128101
Candida albicans similar to transferrin receptor Get druggable targets OG5_128101 All targets in OG5_128101
Schistosoma japonicum ko:K01301 glutamate carboxypeptidase II [EC3.4.17.21], putative Get druggable targets OG5_128101 All targets in OG5_128101
Candida albicans hypothetical protein Get druggable targets OG5_128101 All targets in OG5_128101
Echinococcus multilocularis n acetylated alpha linked acidic dipeptidase 2 Get druggable targets OG5_128101 All targets in OG5_128101
Loa Loa (eye worm) hypothetical protein Get druggable targets OG5_128101 All targets in OG5_128101
Loa Loa (eye worm) hypothetical protein Get druggable targets OG5_128101 All targets in OG5_128101
Loa Loa (eye worm) hypothetical protein Get druggable targets OG5_128101 All targets in OG5_128101
By sequence similarity to non orthologous known druggable targets
Species Potential target Known druggable target Length Alignment span Identity
Candida albicans similar to secretory protein Ssp134p Glutamate carboxypeptidase II   752 aa 717 aa 23.4 %
Candida albicans similar to secretory protein Ssp134p Glutamate carboxypeptidase II   752 aa 717 aa 23.4 %
Obtained from network model

Ranking Plot

Putative Targets List

Species Potential target Raw Global Species
Onchocerca volvulus Fxna peptidase homolog 0.0033 0 0.5
Echinococcus granulosus endoplasmic reticulum metallopeptidase 1 0.0033 0 0.5
Schistosoma mansoni NAALADASE L peptidase (M28 family) 0.032 0.6146 1
Mycobacterium ulcerans lipoprotein aminopeptidase LpqL 0.0045 0.0255 1
Trypanosoma cruzi glutaminyl cyclase, putative 0.0033 0 0.5
Trichomonas vaginalis conserved hypothetical protein 0.0033 0 0.5
Toxoplasma gondii peptidase, M28 family protein 0.0033 0 0.5
Onchocerca volvulus Glutaminyl cyclase homolog 0.0033 0 0.5
Leishmania major hypothetical protein, conserved 0.0033 0 0.5
Brugia malayi nicalin 0.0033 0 0.5
Echinococcus multilocularis n acetylated alpha linked acidic dipeptidase 2 0.0489 0.9745 1
Brugia malayi Peptidase family M28 containing protein 0.0033 0 0.5
Trypanosoma brucei glutaminyl cyclase, putative 0.0033 0 0.5
Loa Loa (eye worm) hypothetical protein 0.0456 0.905 0.905
Echinococcus granulosus endoplasmic reticulum metallopeptidase 1 0.0033 0 0.5
Echinococcus granulosus glutaminyl peptide cyclotransferase 0.0033 0 0.5
Mycobacterium tuberculosis Probable lipoprotein aminopeptidase LpqL 0.0045 0.0255 1
Trichomonas vaginalis Clan MH, family M28, aminopeptidase S-like metallopeptidase 0.0033 0 0.5
Toxoplasma gondii hypothetical protein 0.0033 0 0.5
Brugia malayi leucyl aminopeptidase 0.0033 0 0.5
Trichomonas vaginalis conserved hypothetical protein 0.0033 0 0.5
Onchocerca volvulus Fxna peptidase homolog 0.0033 0 0.5
Leishmania major glutaminyl cyclase, putative 0.0033 0 0.5
Brugia malayi FXNA 0.0033 0 0.5
Onchocerca volvulus 0.0033 0 0.5
Trichomonas vaginalis conserved hypothetical protein 0.0033 0 0.5
Loa Loa (eye worm) hypothetical protein 0.0332 0.6401 0.6401
Trypanosoma cruzi glutaminyl cyclase, putative 0.0033 0 0.5
Onchocerca volvulus Fxna peptidase homolog 0.0033 0 0.5

Activities

Activity type Activity value Assay description Source Reference
EC50 (binding) = 0.62 nM Concentration of the compound required for the neuroprotective effect determined by inhibition of GCP II ChEMBL. 12798312
EC50 (binding) = 0.62 nM Concentration of the compound required for the neuroprotective effect determined by inhibition of GCP II ChEMBL. 12798312
EC50 (functional) = 1.2 nM Neuroprotective effect of the compound against ischemic injury with median effective concentrationin in rat ChEMBL. 15801825
Efflux (functional) = 137 % In vitro effect of compound on Basal Glutamate Efflux at 1.0 nM ChEMBL. 8558536
Efflux (functional) = 151 % In vitro effect of compound on Basal Glutamate Efflux at 0.1 nM ChEMBL. 8558536
Efflux (functional) = 167 % In vitro effect of compound on Basal Glutamate Efflux at 10.0 nM ChEMBL. 8558536
IC50 (binding) = 0.3 nM Inhibition of Glutamate carboxypeptidase II ChEMBL. 12798312
IC50 (binding) = 0.3 nM Inhibition of N-acetyl-L-aspartyl-[3H]-L-glutamate binding to glutamate carboxypeptidase II (GCP II) ChEMBL. 12723961
IC50 (binding) = 0.3 nM Inhibitory concentration against rat brain NAALADase (Folate hydrolase) ChEMBL. 11708918
IC50 (binding) = 0.3 nM In vitro inhibition of N-acetyl-L-aspartyl-[3H]-L-glutamate binding to Glutamate carboxypeptidase II ChEMBL. 15801825
IC50 (binding) = 0.3 nM Inhibition of human recombinant NAALADase ChEMBL. 18060794
IC50 (binding) = 0.3 nM Inhibition of Glutamate carboxypeptidase II ChEMBL. 12798312
IC50 (binding) = 0.3 nM Inhibition of N-acetyl-L-aspartyl-[3H]-L-glutamate binding to glutamate carboxypeptidase II (GCP II) ChEMBL. 12723961
IC50 (binding) = 0.3 nM Inhibitory concentration against rat brain NAALADase (Folate hydrolase) ChEMBL. 11708918
IC50 (binding) = 0.3 nM Inhibition of human recombinant NAALADase ChEMBL. 18060794
IC50 (binding) = 1.1 nM Inhibition of NAALADase activity in human LNCaP cell membranes assessed as inhibition of [3H]NAG conversion to [3H]glutamate after 30 mins by liquid scintillation counting ChEMBL. 23025786
IC50 (binding) = 5.1 nM Inhibitory activity of the compound against expressed rat Glutamate carboxypeptidase II, using a substrate concentration of 5 microM ChEMBL. 11462970
IC50 (binding) = 5.1 nM Inhibitory activity of the compound against expressed rat Glutamate carboxypeptidase II, using a substrate concentration of 5 microM ChEMBL. 11462970
IC50 (binding) = 52 nM Displacement of [125I]23 from PSMA in human LNCAP cells ChEMBL. 26894427
IC50 (binding) = 300 pM Inhibition of GCP-2 (unknown origin) ChEMBL. 22949627
Kd (binding) = 0.4 nM Binding affinity to PSMA in human LNCaP cells assessed as cell surface binding in Tris-buffered saline buffer ChEMBL. 19108655
Kd (binding) = 0.5 nM Binding affinity to PSMA in human PC3 cells assessed as cell surface binding in Tris-buffered saline buffer ChEMBL. 19108655
Ki (binding) = 0.2 nM Inhibitory concentration required against Glutamate carboxypeptidase II ChEMBL. 12798312
Ki (binding) = 0.2 nM In vitro inhibitory activity against glutamate carboxypeptidase II (GCP II) using N-acetyl-L-aspartyl-[3H]-L-glutamate as a substrate ChEMBL. 12723961
Ki (binding) = 0.2 nM Inhibitory concentration required against Glutamate carboxypeptidase II ChEMBL. 12798312
Ki (binding) = 0.2 nM In vitro inhibitory activity against glutamate carboxypeptidase II (GCP II) using N-acetyl-L-aspartyl-[3H]-L-glutamate as a substrate ChEMBL. 12723961
Ki (binding) = 0.275 nM Compound was tested for inhibition of the Folate hydrolase ChEMBL. 8558536
Ki (binding) = 0.275 nM Compound was tested for inhibition of the Folate hydrolase ChEMBL. 8558536
Ki (binding) = 0.28 nM Inhibition of antiTEV-tagged GCP2 extracellular portion (aa 44-750) (unknown origin) using folyl-di-L-glutamate as substrate by HPLC-based enzymatic assay ChEMBL. 25923815
Ki (binding) = 0.3 nM Binding affinity to NAALADase ChEMBL. 23025786
Ki (binding) = 0.4 nM Inhibition of NAALADase activity in human LNCaP cell membranes assessed as inhibition of [3H]NAG conversion to [3H]glutamate after 30 mins by liquid scintillation counting ChEMBL. 23025786
Ki (binding) = 1.4 nM In vitro inhibitory activity against human Glutamate carboxypeptidase II by using fluorescent assay ChEMBL. 15027864
Ki (binding) = 1.4 nM In vitro inhibitory activity against human Glutamate carboxypeptidase II by using fluorescent assay ChEMBL. 15027864
Ki (binding) = 31.2 nM Displacement of [123I]-DCIT from PSMA in human LNCaP cells after 1 hr by gamma counting ChEMBL. 24063417
Release (functional) = 316 In vitro effect of the compound KCL-Evoked Giutamate at 0.1 nM ChEMBL. 8558536
Release (functional) = 368 In vitro effect of the compound KCL-Evoked Glutamate at 1.0 nM ChEMBL. 8558536
Release (functional) = 437 In vitro effect of the compound KCL-Evoked Giutamate at 10.0 nM ChEMBL. 8558536
Stabilty (ADMET) = 85 % Metabolic stability in mouse plasma assessed as compound remaining at 10 uM after 1 hr by LC/MS/MS analysis ChEMBL. 26930119
Stabilty (ADMET) = 91 % Metabolic stability in human liver microsomes assessed as compound remaining at 10 uM after 1 hr by LC/MS/MS analysis ChEMBL. 26930119

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

Bibliographic References

14 literature references were collected for this gene.

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