Detailed information for compound 989642

Basic information

Technical information
  • TDR Targets ID: 989642
  • Name: (2S)-2-[[4-[4-(2-amino-4-oxo-3H-thieno[5,4-d] pyrimidin-6-yl)butyl]benzoyl]amino]pentanedio ic acid
  • MW: 472.514 | Formula: C22H24N4O6S
  • H donors: 5 H acceptors: 6 LogP: 2.05 Rotable bonds: 12
    Rule of 5 violations (Lipinski): 1
  • SMILES: OC(=O)CC[C@@H](C(=O)O)NC(=O)c1ccc(cc1)CCCCc1sc2c(c1)c(=O)[nH]c(n2)N
  • InChi: 1S/C22H24N4O6S/c23-22-25-19(30)15-11-14(33-20(15)26-22)4-2-1-3-12-5-7-13(8-6-12)18(29)24-16(21(31)32)9-10-17(27)28/h5-8,11,16H,1-4,9-10H2,(H,24,29)(H,27,28)(H,31,32)(H3,23,25,26,30)/t16-/m0/s1
  • InChiKey: KVBZUTNKUVNMNN-INIZCTEOSA-N  


Substructure search Similarity search

Network

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Synonyms

  • (2S)-2-[[[4-[4-(2-amino-4-oxo-3H-thieno[5,4-d]pyrimidin-6-yl)butyl]phenyl]-oxomethyl]amino]pentanedioic acid
  • (2S)-2-[[4-[4-(2-amino-4-keto-3H-thieno[5,4-d]pyrimidin-6-yl)butyl]benzoyl]amino]glutaric acid
  • (2S)-2-[[4-[4-(2-amino-4-oxo-3H-thieno[5,4-d]pyrimidin-6-yl)butyl]phenyl]carbonylamino]pentanedioic acid

Targets

Known targets for this compound

Species Target name Source Bibliographic reference
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
Species Potential target Known druggable target/s Ortholog Group
Onchocerca volvulus Get druggable targets OG5_126894 All targets in OG5_126894
Mycobacterium tuberculosis Probable phosphoribosylformylglycinamidine CYCLO-ligase PurM (AIRS) (phosphoribosyl-aminoimidazole synthetase) (air synthase) Get druggable targets OG5_126894 All targets in OG5_126894
Mycobacterium tuberculosis Probable phosphoribosylamine--glycine ligase PurD (GARS) (glycinamide ribonucleotide synthetase) (phosphoribosylglycinamide synt Get druggable targets OG5_126894 All targets in OG5_126894
Mycobacterium leprae PROBABLE PHOSPHORIBOSYLAMINE--GLYCINE LIGASE PURD (GARS) (GLYCINAMIDE RIBONUCLEOTIDE SYNTHETASE) (PHOSPHORIBOSYLGLYCINAMIDE SYNT Get druggable targets OG5_126894 All targets in OG5_126894
Mycobacterium ulcerans phosphoribosylamine--glycine ligase Get druggable targets OG5_126894 All targets in OG5_126894
Candida albicans N terminus of ADE5,7 bifunctional ligase Get druggable targets OG5_126894 All targets in OG5_126894
Mycobacterium leprae PROBABLE PHOSPHORIBOSYLFORMYLGLYCINAMIDINE CYCLO-LIGASE PURM (AIRS) (PHOSPHORIBOSYL-AMINOIMIDAZOLE SYNTHETASE) (AIR SYNTHASE) Get druggable targets OG5_126894 All targets in OG5_126894
Candida albicans purine biosynthesis Get druggable targets OG5_126894 All targets in OG5_126894
Onchocerca volvulus Get druggable targets OG5_126894 All targets in OG5_126894
Wolbachia endosymbiont of Brugia malayi phosphoribosylamine--glycine ligase Get druggable targets OG5_126894 All targets in OG5_126894
Mycobacterium ulcerans phosphoribosylaminoimidazole synthetase Get druggable targets OG5_126894 All targets in OG5_126894
Candida albicans ADE5,7 bifunctional ligase Get druggable targets OG5_126894 All targets in OG5_126894
Wolbachia endosymbiont of Brugia malayi phosphoribosylaminoimidazole synthetase Get druggable targets OG5_126894 All targets in OG5_126894
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
Loa Loa (eye worm) hypothetical protein 0.0029 0.0006 1
Echinococcus multilocularis Ankyrin 0.0029 0.0006 0.0006
Echinococcus multilocularis nuclear factor of activated T cells 5 0.0439 1 1
Echinococcus granulosus Ankyrin 0.0029 0.0006 0.0006
Schistosoma mansoni ankyrin 23/unc44 0.0029 0.000000040358 0.0001
Brugia malayi Protein kinase domain containing protein 0.0029 0.0015 1
Mycobacterium leprae PROBABLE PHOSPHORIBOSYLAMINE--GLYCINE LIGASE PURD (GARS) (GLYCINAMIDE RIBONUCLEOTIDE SYNTHETASE) (PHOSPHORIBOSYLGLYCINAMIDE SYNT 0.0359 0.8058 1
Onchocerca volvulus 0.0079 0.1236 1
Mycobacterium ulcerans phosphoribosylamine--glycine ligase 0.0359 0.8058 1
Onchocerca volvulus 0.0063 0.0843 0.6822
Echinococcus granulosus ankyrin repeat and death domain containing protein 0.0029 0.000000040358 0.000000040358
Mycobacterium tuberculosis Probable phosphoribosylformylglycinamidine CYCLO-ligase PurM (AIRS) (phosphoribosyl-aminoimidazole synthetase) (air synthase) 0.0079 0.1236 1
Wolbachia endosymbiont of Brugia malayi phosphoribosylamine--glycine ligase 0.0359 0.8058 1
Echinococcus multilocularis ankyrin repeat and death domain containing protein 0.0029 0.000000040358 0.000000040358
Schistosoma mansoni retinoblastoma-binding protein 4 (rbbp4) 0.0029 0.0006 1

Activities

Activity type Activity value Assay description Source Reference
IC50 (functional) = 4.9 nM Antiproliferative activity against human KB cells expressing human reduced folate carrier/folate receptor alpha after 96 hrs by celltiter-blue cell viability assay ChEMBL. 19371039
IC50 (functional) = 4.9 nM Growth inhibition of human KB cells expressing RFC, FRalpha and PCFT after 96 hrs ChEMBL. 20085328
IC50 (functional) = 5.9 nM Antiproliferative activity against human IGROV1 cells expressing human reduced folate carrier/folate receptor alpha after 96 hrs by celltiter-blue cell viability assay ChEMBL. 19371039
IC50 (functional) = 5.9 nM Growth inhibition of human IGROV1 cells expressing RFC, FRalpha and PCFT after 96 hrs ChEMBL. 20085328
IC50 (binding) = 13.3 nM Inhibition of GARFTase in human KB cells assessed as inhibition of incorporation of [14C]glycine into [14C]formyl GAR after 30 mins in presence of azaserine ChEMBL. 19371039
IC50 (functional) > 1000 nM Antiproliferative activity against human KB cells expressing human reduced folate carrier/folate receptor alpha after 96 hrs by celltiter-blue cell viability assay in presence of folic acid ChEMBL. 19371039
IC50 (functional) > 1000 nM Antiproliferative activity against human IGROV1 cells expressing human reduced folate carrier/folate receptor alpha after 96 hrs by celltiter-blue cell viability assay in presence of folic acid ChEMBL. 19371039
IC50 (binding) = 5.51 uM Inhibition of mouse recombinant GARFTase ChEMBL. 19371039
IC50 (binding) = 13.3 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) = 5510 uM Inhibition of mouse recombinant GARFtase assessed as FGAR formation by spectrophotometry ChEMBL. 20085328
RBA (binding) > 0.8 Displacement of [3H]folic acid from human folate receptor alpha in chinese hamster RT16 cells assessed as relative binding affinity relative to folic acid ChEMBL. 19371039
RBA (binding) > 0.8 Displacement of [3H]folic acid from human folate receptor beta in chinese hamster D4 cells assessed as relative binding affinity relative to folic acid ChEMBL. 19371039

Phenotypes

Whole-cell/tissue/organism interactions

Species name Source Reference Is orphan
Homo sapiens ChEMBL23 19371039

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

2 literature references were collected for this gene.

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