Detailed information for compound 247198

Basic information

Technical information
  • TDR Targets ID: 247198
  • Name: (2S)-2-[[4-[2-(2-amino-4-oxo-5,6,7,8-tetrahyd ro-1H-pyrido[2,3-d]pyrimidin-6-yl)ethyl]benzo yl]amino]pentanedioic acid
  • MW: 443.453 | Formula: C21H25N5O6
  • H donors: 6 H acceptors: 8 LogP: 1.52 Rotable bonds: 10
    Rule of 5 violations (Lipinski): 2
  • SMILES: OC(=O)CC[C@H](C(=O)O)NC(=O)c1ccc(cc1)CCC1CNc2c(C1)c(O)nc(n2)N
  • InChi: 1S/C21H25N5O6/c22-21-25-17-14(19(30)26-21)9-12(10-23-17)2-1-11-3-5-13(6-4-11)18(29)24-15(20(31)32)7-8-16(27)28/h3-6,12,15H,1-2,7-10H2,(H,24,29)(H,27,28)(H,31,32)(H4,22,23,25,26,30)/t12?,15-/m0/s1
  • InChiKey: ZUQBAQVRAURMCL-CVRLYYSRSA-N  


Substructure search Similarity search

Network

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Synonyms

  • (2S)-2-[[[4-[2-(2-amino-4-oxo-5,6,7,8-tetrahydro-1H-pyrido[2,3-d]pyrimidin-6-yl)ethyl]phenyl]-oxomethyl]amino]pentanedioic acid
  • (2S)-2-[[4-[2-(2-azanyl-4-oxo-5,6,7,8-tetrahydro-1H-pyrido[2,3-d]pyrimidin-6-yl)ethyl]phenyl]carbonylamino]pentanedioic acid
  • (2S)-2-[[4-[2-(2-amino-4-keto-5,6,7,8-tetrahydro-1H-pyrido[2,3-d]pyrimidin-6-yl)ethyl]benzoyl]amino]glutaric acid
  • lometrexol
  • (2S)-2-[[4-[2-(2-amino-4-oxo-5,6,7,8-tetrahydro-1H-pyrido[5,6-e]pyrimidin-6-yl)ethyl]benzoyl]amino]pentanedioic acid
  • (2S)-2-[[[4-[2-(2-amino-4-oxo-5,6,7,8-tetrahydro-1H-pyrido[5,6-e]pyrimidin-6-yl)ethyl]phenyl]-oxomethyl]amino]pentanedioic acid
  • (2S)-2-[[4-[2-(2-amino-4-keto-5,6,7,8-tetrahydro-1H-pyrido[5,6-e]pyrimidin-6-yl)ethyl]benzoyl]amino]glutaric acid
  • (2S)-2-[[4-[2-(2-amino-4-oxo-5,6,7,8-tetrahydro-1H-pyrido[5,6-e]pyrimidin-6-yl)ethyl]phenyl]carbonylamino]pentanedioic acid
  • 116387-29-2
  • 95693-76-8
  • DATHF
  • DDATHF
  • L-Glutamic acid, N-(4-(2-(2-amino-1,4,5,6,7,8-hexahydro-4-oxopyrido(2,3-d)pyrimidin-6-yl)ethyl)benzoyl)-
  • Pyrido(2,3-d)pyrimidine, L-glutamic acid deriv.
  • 5,10-Dideaza-5,6,7,8-tetrahydrofolic acid

Targets

Known targets for this compound

Species Target name Source Bibliographic reference
Leishmania major dihydrofolate reductase-thymidylate synthase Curated by TDR Targets References
Leishmania major pteridine reductase 1 Curated by TDR Targets References

Predicted pathogen targets for this compound

By orthology
Species Potential target Known druggable target/s Ortholog Group
Toxoplasma gondii bifunctional dihydrofolate reductase-thymidylate synthase Get druggable targets OG5_127385 All targets in OG5_127385
Plasmodium knowlesi bifunctional dihydrofolate reductase-thymidylate synthase, putative Get druggable targets OG5_127385 All targets in OG5_127385
Brugia malayi thymidylate synthase Get druggable targets OG5_127385 All targets in OG5_127385
Schistosoma mansoni bifunctional dihydrofolate reductase-thymidylate synthase Get druggable targets OG5_127385 All targets in OG5_127385
Plasmodium falciparum bifunctional dihydrofolate reductase-thymidylate synthase Get druggable targets OG5_127385 All targets in OG5_127385
Trypanosoma brucei dihydrofolate reductase-thymidylate synthase Get druggable targets OG5_127385 All targets in OG5_127385
Leishmania infantum pteridine reductase 1 Get druggable targets OG5_133937 All targets in OG5_133937
Candida albicans Thymidylate synthase capable of functional substitution for S. cerevisiae CDC21 (YOR074C) Get druggable targets OG5_127385 All targets in OG5_127385
Babesia bovis dihydrofolate reductase/thymidilate synthase Get druggable targets OG5_127385 All targets in OG5_127385
Mycobacterium ulcerans thymidylate synthase Get druggable targets OG5_127385 All targets in OG5_127385
Onchocerca volvulus Get druggable targets OG5_127385 All targets in OG5_127385
Leishmania braziliensis dihydrofolate reductase-thymidylate synthase Get druggable targets OG5_127385 All targets in OG5_127385
Neospora caninum Bifunctional dihydrofolate reductase-thymidylate synthase, related Get druggable targets OG5_127385 All targets in OG5_127385
Trypanosoma brucei pteridine reductase 1 Get druggable targets OG5_133937 All targets in OG5_133937
Schistosoma japonicum hypothetical protein Get druggable targets OG5_127385 All targets in OG5_127385
Trypanosoma brucei gambiense dihydrofolate reductase-thymidylate synthase Get druggable targets OG5_127385 All targets in OG5_127385
Cryptosporidium hominis chain A, crystal structure of Dhfr Get druggable targets OG5_127385 All targets in OG5_127385
Leishmania braziliensis pteridine reductase 1 Get druggable targets OG5_133937 All targets in OG5_133937
Leishmania major dihydrofolate reductase-thymidylate synthase Get druggable targets OG5_127385 All targets in OG5_127385
Mycobacterium tuberculosis Probable thymidylate synthase ThyA (ts) (TSASE) Get druggable targets OG5_127385 All targets in OG5_127385
Schistosoma japonicum ko:K00560 thymidylate synthase [EC2.1.1.45], putative Get druggable targets OG5_127385 All targets in OG5_127385
Leishmania donovani dihydrofolate reductase-thymidylate synthase Get druggable targets OG5_127385 All targets in OG5_127385
Theileria parva dihydrofolate reductase-thymidylate synthase, putative Get druggable targets OG5_127385 All targets in OG5_127385
Trypanosoma congolense pteridine reductase 1 Get druggable targets OG5_133937 All targets in OG5_133937
Echinococcus granulosus thymidylate synthase Get druggable targets OG5_127385 All targets in OG5_127385
Leishmania mexicana dihydrofolate reductase-thymidylate synthase Get druggable targets OG5_127385 All targets in OG5_127385
Leishmania major pteridine reductase 1 Get druggable targets OG5_133937 All targets in OG5_133937
Plasmodium yoelii thymidylate synthase, putative Get druggable targets OG5_127385 All targets in OG5_127385
Candida albicans Thymidylate synthase capable of functional substitution for S. cerevisiae CDC21 (YOR074C) Get druggable targets OG5_127385 All targets in OG5_127385
Leishmania donovani pteridine reductase 1 Get druggable targets OG5_133937 All targets in OG5_133937
Leishmania infantum dihydrofolate reductase-thymidylate synthase Get druggable targets OG5_127385 All targets in OG5_127385
Loa Loa (eye worm) thymidylate synthase Get druggable targets OG5_127385 All targets in OG5_127385
Leishmania mexicana pteridine reductase 1 Get druggable targets OG5_133937 All targets in OG5_133937
Cryptosporidium parvum dihydrofolate reductase-thymidylate synthase Get druggable targets OG5_127385 All targets in OG5_127385
Plasmodium berghei bifunctional dihydrofolate reductase-thymidylate synthase, putative Get druggable targets OG5_127385 All targets in OG5_127385
Trypanosoma cruzi dihydrofolate reductase-thymidylate synthase Get druggable targets OG5_127385 All targets in OG5_127385
Echinococcus multilocularis thymidylate synthase Get druggable targets OG5_127385 All targets in OG5_127385
Plasmodium vivax bifunctional dihydrofolate reductase-thymidylate synthase, putative Get druggable targets OG5_127385 All targets in OG5_127385
Mycobacterium leprae PROBABLE THYMIDYLATE SYNTHASE THYA (TS) (TSASE) Get druggable targets OG5_127385 All targets in OG5_127385
By sequence similarity to non orthologous known druggable targets
Species Potential target Known druggable target Length Alignment span Identity
Plasmodium falciparum 3-oxoacyl-[acyl-carrier-protein] reductase pteridine reductase 1 288 aa 281 aa 25.3 %
Obtained from network model

Ranking Plot

Putative Targets List

Species Potential target Raw Global Species

Activities

Activity type Activity value Assay description Source Reference
IC50 (functional) = 16 nM In vitro antitumor activity was assessed from rate of cell growth of CCRF/CEM cell line ChEMBL. 8027993
IC50 (functional) = 0.007 ug ml-1 The compound was tested for its cytotoxicity against CCRF-CEM human leukemic cells using 72 hrs assay ChEMBL. No reference
IC50 (functional) = 0.007 ug ml-1 Tested for the growth inhibition of CCRF-CEM, a human T-cell derived lymphoblastic leukemic cell line ChEMBL. No reference
IC50 (functional) = 0.005 uM Compound was tested for its antitumor activity against human lymphoblastic leukemic cells(CCRF-CEM) in vitro ChEMBL. 2738886
IC50 (functional) = 0.008 uM Compound was tested for its antitumor activity against human lymphoblastic leukemic cells(CCRF-CEM) in vitro ChEMBL. 2738886
IC50 (functional) = 0.016 uM Cytotoxicity of the compound against human lymphoblastic leukemic CCRF-CEM cell line was evaluated as the concentration required for 50% inhibition of the growth of the control value ChEMBL. 1552503
IC50 (functional) = 0.02 uM Compound was tested for its antitumor activity against human lymphoblastic leukemic cells(CCRF-CEM) in vitro ChEMBL. 2738886
IC50 (binding) = 0.22 uM Ability to inhibit glycinamide ribonucleotide transformylase (GAR-Tfase) in vitro, using hog liver with (6R)-10-formyl-FH4 as cofactor ChEMBL. 8027993
IC50 (functional) = 1.5 uM Ability to inhibit [3H]-methotrexate transport into MOLT-4 cells in vitro ChEMBL. 8027993
IC50 (functional) = 18 uM Ability to inhibit growth of MCF-7 human breast adenocarcinoma in vitro ChEMBL. 8027993
k (binding) = 32 First order catalytic rate constants (k) was determined from mouse liver Folyl-polyglutamate synthase ChEMBL. 2738886
Ki (binding) = 0.00000012 uM Inhibitory activity against glycinamide ribonucleotide formyltransferase (GARFT) from L1210 murine leukemic cells ChEMBL. No reference
Ki (functional) = 0.12 uM Tested for the inhibition of trifunctional Glycinamide ribonucleotide formyltransferase isolated from murine L1210 cells. ChEMBL. No reference
Ki (binding) = 0.13 uM Tested for the inhibition of recombinant human monofunctional Glycinamide ribonucleotide formyltransferase ChEMBL. No reference
Km (binding) = 16.4 uM Substrate activity of the compound against folylpolyglutamate synthetase isolated from hog liver ChEMBL. No reference
Km (ADMET) = 17.5 uM Km of Hog folylpolyglutamate synthase (FPGS) relative to aminopterin ChEMBL. 8027993
Km app (binding) = 7.3 Apparent catalytic rate constants (Km) owas determined from mouse liver Folyl-polyglutamate synthase ChEMBL. 2738886
Ratio (binding) = 60 Ratio of Vmax/Km was evaluated. ChEMBL. No reference
Vmax (binding) = 1.26 Catalytic rate constants (Vmax) was determined from mouse liver Folyl-polyglutamate synthase ChEMBL. 2738886
Vmax (ADMET) = 97 % Vmax of Hog folylpolyglutamate synthase (FPGS) relative to aminopterin ChEMBL. 8027993
Vmax (binding) = 977 nM hr-1 mg-1 Substrate activity of the compound against folylpolyglutamate synthetase isolated from hog liver ChEMBL. No reference

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:

Affected Entity Phenotypic quality Occurs in Occurs at Evidence Observed in Targets
growth (GO:0040007) decreased time (PATO:0000716) single cell organism (CARO:0000064) promastigote (BTO:0001124) inferred from bioassay (ECO:0000094) Leishmania major 25954  
Annotator: aaronjr@u.washington.edu Comment: Drug: 700-47-0; Drug: 704-61-0; Drug: 708-74-7; Drug: 945-24-4; Drug: 1026-36-4; Drug: 1597-01-9; Drug: 1899-40-7; Drug: 2432-24-8; Drug: 2440-80-4; Drug: 3977-17-1; Drug: 5774-32-3; Drug: 6954-23-0; Drug: 6973-01-9; Drug: 7319-50-8; Drug: 14684-54-9; Drug: 17005-34-4; Drug: 17005-35-5; Drug: 19152-86-4; Drug: 26398-12-9; Drug: 34244-78-5; Drug: 34244-80-9; Drug: 36804-91-8; Drug: 38713-63-2; Drug: 38713-64-3; Drug: 38713-65-4; Drug: 47066-05-7; Drug: 50691-65-1; Drug: 51395-54-1; Drug: 51583-00-7; Drug: 52128-15-1; Drug: 53219-56-0; Drug: 53274-34-3; Drug: 54798-36-6; Drug: 58091-86-4; Drug: 61267-65-0; Drug: 61267-67-2; Drug: 73978-42-4; Drug: 73978-43-5; Drug: 73978-44-6; Drug: 89977-50-4; Drug: 104422-58-4; Drug: 104422-59-5; Drug: 107174-41-4; Drug: 160602-03-9; Drug: 160602-12-0; Drug: 200127-49-7; Drug: 200127-50-0; Drug: 200127-51-1; Drug: 200127-52-2; Drug: 200127-53-3; Drug: 200127-54-4; Drug: 200127-55-5; Drug: 200127-57-7; Drug: 200127-58-8; Drug: 200127-59-9; Drug: 200127-60-2; Drug: 200127-61-3; Drug: 200127-62-4; Drug: 200127-63-5. chemical inhibition with DHFR and PTR1 inhibitors leads to slow growth of Leishmania sp. in cell assay; References: 9371081 9398595
catalytic activity (GO:0003824) decreased (PATO:0000468) in vitro (MI:0492) inferred from specific protein inhibition (ECO:0000020) Leishmania major 25954  
Annotator: aaronjr@u.washington.edu Comment: Drug: 700-47-0; Drug: 704-61-0; Drug: 708-74-7; Drug: 945-24-4; Drug: 1026-36-4; Drug: 1597-01-9; Drug: 1899-40-7; Drug: 2432-24-8; Drug: 2440-80-4; Drug: 3977-17-1; Drug: 5774-32-3; Drug: 6954-23-0; Drug: 6973-01-9; Drug: 7319-50-8; Drug: 14684-54-9; Drug: 17005-34-4; Drug: 17005-35-5; Drug: 19152-86-4; Drug: 26398-12-9; Drug: 34244-78-5; Drug: 34244-80-9; Drug: 36804-91-8; Drug: 38713-63-2; Drug: 38713-64-3; Drug: 38713-65-4; Drug: 47066-05-7; Drug: 50691-65-1; Drug: 51395-54-1; Drug: 51583-00-7; Drug: 52128-15-1; Drug: 53219-56-0; Drug: 53274-34-3; Drug: 54798-36-6; Drug: 58091-86-4; Drug: 61267-65-0; Drug: 61267-67-2; Drug: 73978-42-4; Drug: 73978-43-5; Drug: 73978-44-6; Drug: 89977-50-4; Drug: 104422-58-4; Drug: 104422-59-5; Drug: 107174-41-4; Drug: 160602-03-9; Drug: 160602-12-0; Drug: 200127-49-7; Drug: 200127-50-0; Drug: 200127-51-1; Drug: 200127-52-2; Drug: 200127-53-3; Drug: 200127-54-4; Drug: 200127-55-5; Drug: 200127-57-7; Drug: 200127-58-8; Drug: 200127-59-9; Drug: 200127-60-2; Drug: 200127-61-3; Drug: 200127-62-4; Drug: 200127-63-5. chemical inhibition with DHFR and PTR1 inhibitors leads to reduced enzyme activity in vitro; References: 9371081 9398595
growth (GO:0040007) decreased time (PATO:0000716) single cell organism (CARO:0000064) promastigote (BTO:0001124) inferred from bioassay (ECO:0000094) Leishmania major 21977  
Annotator: aaronjr@u.washington.edu Comment: Drug: 700-47-0; Drug: 704-61-0; Drug: 708-74-7; Drug: 945-24-4; Drug: 1026-36-4; Drug: 1597-01-9; Drug: 1899-40-7; Drug: 2432-24-8; Drug: 2440-80-4; Drug: 3977-17-1; Drug: 5774-32-3; Drug: 6954-23-0; Drug: 6973-01-9; Drug: 7319-50-8; Drug: 14684-54-9; Drug: 17005-34-4; Drug: 17005-35-5; Drug: 19152-86-4; Drug: 26398-12-9; Drug: 34244-78-5; Drug: 34244-80-9; Drug: 36804-91-8; Drug: 38713-63-2; Drug: 38713-64-3; Drug: 38713-65-4; Drug: 47066-05-7; Drug: 50691-65-1; Drug: 51395-54-1; Drug: 51583-00-7; Drug: 52128-15-1; Drug: 53219-56-0; Drug: 53274-34-3; Drug: 54798-36-6; Drug: 58091-86-4; Drug: 61267-65-0; Drug: 61267-67-2; Drug: 73978-42-4; Drug: 73978-43-5; Drug: 73978-44-6; Drug: 89977-50-4; Drug: 104422-58-4; Drug: 104422-59-5; Drug: 107174-41-4; Drug: 160602-03-9; Drug: 160602-12-0; Drug: 200127-49-7; Drug: 200127-50-0; Drug: 200127-51-1; Drug: 200127-52-2; Drug: 200127-53-3; Drug: 200127-54-4; Drug: 200127-55-5; Drug: 200127-57-7; Drug: 200127-58-8; Drug: 200127-59-9; Drug: 200127-60-2; Drug: 200127-61-3; Drug: 200127-62-4; Drug: 200127-63-5. chemical inhibition with DHFR and PTR1 inhibitors leads to slow growth of Leishmania sp. in cell assay; References: 9371081 9398595
catalytic activity (GO:0003824) decreased (PATO:0000468) in vitro (MI:0492) inferred from specific protein inhibition (ECO:0000020) Leishmania major 21977  
Annotator: aaronjr@u.washington.edu Comment: Drug: 700-47-0; Drug: 704-61-0; Drug: 708-74-7; Drug: 945-24-4; Drug: 1026-36-4; Drug: 1597-01-9; Drug: 1899-40-7; Drug: 2432-24-8; Drug: 2440-80-4; Drug: 3977-17-1; Drug: 5774-32-3; Drug: 6954-23-0; Drug: 6973-01-9; Drug: 7319-50-8; Drug: 14684-54-9; Drug: 17005-34-4; Drug: 17005-35-5; Drug: 19152-86-4; Drug: 26398-12-9; Drug: 34244-78-5; Drug: 34244-80-9; Drug: 36804-91-8; Drug: 38713-63-2; Drug: 38713-64-3; Drug: 38713-65-4; Drug: 47066-05-7; Drug: 50691-65-1; Drug: 51395-54-1; Drug: 51583-00-7; Drug: 52128-15-1; Drug: 53219-56-0; Drug: 53274-34-3; Drug: 54798-36-6; Drug: 58091-86-4; Drug: 61267-65-0; Drug: 61267-67-2; Drug: 73978-42-4; Drug: 73978-43-5; Drug: 73978-44-6; Drug: 89977-50-4; Drug: 104422-58-4; Drug: 104422-59-5; Drug: 107174-41-4; Drug: 160602-03-9; Drug: 160602-12-0; Drug: 200127-49-7; Drug: 200127-50-0; Drug: 200127-51-1; Drug: 200127-52-2; Drug: 200127-53-3; Drug: 200127-54-4; Drug: 200127-55-5; Drug: 200127-57-7; Drug: 200127-58-8; Drug: 200127-59-9; Drug: 200127-60-2; Drug: 200127-61-3; Drug: 200127-62-4; Drug: 200127-63-5. chemical inhibition with DHFR and PTR1 inhibitors leads to reduced enzyme activity in vitro; References: 9371081 9398595

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

5 literature references were collected for this gene.

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