Detailed information for compound 1718705

Basic information

Technical information
  • Name: Unnamed compound
  • MW: 428.458 | Formula: C25H21FN4O2
  • H donors: 1 H acceptors: 2 LogP: 5.48 Rotable bonds: 6
    Rule of 5 violations (Lipinski): 1
  • SMILES: COc1cc(ccc1n1cnc(c1)C)Nc1cccc2c1nc(o2)Cc1ccc(cc1)F
  • InChi: 1S/C25H21FN4O2/c1-16-14-30(15-27-16)21-11-10-19(13-23(21)31-2)28-20-4-3-5-22-25(20)29-24(32-22)12-17-6-8-18(26)9-7-17/h3-11,13-15,28H,12H2,1-2H3
  • InChiKey: NPYAHWBZOQFCKU-UHFFFAOYSA-N  

Network

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Synonyms

No synonyms found for this compound

Targets

Known targets for this compound

Species Target name Source Bibliographic reference
Homo sapiens APH1B gamma secretase subunit Starlite/ChEMBL References
Homo sapiens APH1A gamma secretase subunit References
Homo sapiens presenilin 1 References
Homo sapiens presenilin 2 References
Homo sapiens presenilin enhancer gamma secretase subunit References
Homo sapiens nicastrin References

Predicted pathogen targets for this compound

By orthology
Species Potential target Known druggable target/s Ortholog Group
Echinococcus multilocularis Nicastrin Get druggable targets OG5_131095 All targets in OG5_131095
Schistosoma mansoni subfamily A22A unassigned peptidase (A22 family) Get druggable targets OG5_128959 All targets in OG5_128959
Schistosoma mansoni hypothetical protein Get druggable targets OG5_131095 All targets in OG5_131095
Echinococcus granulosus gamma secretase subunit aph 1 Get druggable targets OG5_130831 All targets in OG5_130831
Loa Loa (eye worm) gamma-secretase subunit aph-1 Get druggable targets OG5_130831 All targets in OG5_130831
Schistosoma japonicum ko:K06171 nicastrin, putative Get druggable targets OG5_131095 All targets in OG5_131095
Loa Loa (eye worm) hypothetical protein Get druggable targets OG5_131095 All targets in OG5_131095
Trichomonas vaginalis Clan AD, family A22, presenilin-like aspartic peptidase Get druggable targets OG5_128959 All targets in OG5_128959
Brugia malayi gamma-secretase subunit aph-1 Get druggable targets OG5_130831 All targets in OG5_130831
Echinococcus granulosus Nicastrin Get druggable targets OG5_131095 All targets in OG5_131095
Echinococcus multilocularis Nicastrin Get druggable targets OG5_131095 All targets in OG5_131095
Brugia malayi Presenilin family protein Get druggable targets OG5_128959 All targets in OG5_128959
Echinococcus multilocularis presenilin Get druggable targets OG5_128959 All targets in OG5_128959
Entamoeba histolytica presenilin 1 peptidase, putative Get druggable targets OG5_128959 All targets in OG5_128959
Trichomonas vaginalis Clan AD, family A22, presenilin-like aspartic peptidase Get druggable targets OG5_128959 All targets in OG5_128959
Echinococcus granulosus presenilin Get druggable targets OG5_128959 All targets in OG5_128959
Trichomonas vaginalis Clan AD, family A22, presenilin-like aspartic peptidase Get druggable targets OG5_128959 All targets in OG5_128959
Leishmania donovani presenilin-like aspartic peptidase, putative Get druggable targets OG5_128959 All targets in OG5_128959
Leishmania mexicana presenilin-like aspartic peptidase, putative,presenilin-like aspartic peptidase, clan AD, family A22A, putative Get druggable targets OG5_128959 All targets in OG5_128959
Schistosoma japonicum ko:K04505 presenilin-1, putative Get druggable targets OG5_128959 All targets in OG5_128959
Schistosoma japonicum ko:K06172 anterior pharynx defective 1, putative Get druggable targets OG5_130831 All targets in OG5_130831
Trypanosoma cruzi presenilin-like aspartic peptidase, putative Get druggable targets OG5_128959 All targets in OG5_128959
Trichomonas vaginalis Nicastrin precursor, putative Get druggable targets OG5_131095 All targets in OG5_131095
Trichomonas vaginalis Nicastrin precursor, putative Get druggable targets OG5_131095 All targets in OG5_131095
Echinococcus multilocularis gamma secretase subunit aph 1 Get druggable targets OG5_130831 All targets in OG5_130831
Brugia malayi gamma-secretase subunit pen-2 Get druggable targets OG5_132844 All targets in OG5_132844
Leishmania infantum presenilin-like aspartic peptidase, putative,presenilin-like aspartic peptidase, clan AD, family A22A, putative Get druggable targets OG5_128959 All targets in OG5_128959
Trypanosoma brucei gambiense presenilin-like aspartic peptidase, putative,presenilin-like aspartic peptidase, clan AD, family A22A, putative Get druggable targets OG5_128959 All targets in OG5_128959
Schistosoma mansoni gamma-secretase subunit aph-1 Get druggable targets OG5_130831 All targets in OG5_130831
Leishmania braziliensis presenilin-like aspartic peptidase, putative,presenilin-like aspartic peptidase, clan AD, family A22A, putative Get druggable targets OG5_128959 All targets in OG5_128959
Trypanosoma brucei presenilin-like aspartic peptidase, putative Get druggable targets OG5_128959 All targets in OG5_128959
Echinococcus multilocularis presenilin enhancer 2 Get druggable targets OG5_132844 All targets in OG5_132844
Loa Loa (eye worm) gamma-secretase subunit pen-2 Get druggable targets OG5_132844 All targets in OG5_132844
Echinococcus granulosus presenilin enhancer 2 Get druggable targets OG5_132844 All targets in OG5_132844
Brugia malayi hypothetical protein Get druggable targets OG5_131095 All targets in OG5_131095
Trypanosoma congolense presenilin-like aspartic peptidase, putative Get druggable targets OG5_128959 All targets in OG5_128959
Leishmania major presenilin-like aspartic peptidase, putative,presenilin-like aspartic peptidase, clan AD, family A22A, putative Get druggable targets OG5_128959 All targets in OG5_128959
Brugia malayi hypothetical protein Get druggable targets OG5_131095 All targets in OG5_131095
Trypanosoma cruzi presenilin-like aspartic peptidase, putative Get druggable targets OG5_128959 All targets in OG5_128959

By sequence similarity to non orthologous known druggable targets
Species Potential target Known druggable target Length Alignment span Identity
Echinococcus granulosus oxalate:formate antiporter presenilin enhancer gamma secretase subunit 101 aa 98 aa 29.6 %

Obtained from network model

Ranking Plot


Putative Targets List


Species Potential target Raw Global Species
Echinococcus granulosus kelch ECH associated protein 1 like 0.0489 0.8256 0.8256
Loa Loa (eye worm) gamma-secretase subunit pen-2 0.0233 0.3921 0.3921
Echinococcus multilocularis Nicastrin 0.0121 0.2024 0.2024
Trypanosoma cruzi Aph-1 protein, putative 0.0231 0.3881 0.9136
Echinococcus multilocularis kelch ECH associated protein 1 0.0489 0.8256 0.8256
Trypanosoma cruzi presenilin-like aspartic peptidase, putative 0.0248 0.4179 1
Loa Loa (eye worm) hypothetical protein 0.0121 0.2024 0.2024
Echinococcus multilocularis presenilin enhancer 2 0.0233 0.3921 0.3921
Loa Loa (eye worm) presenilin spe-4 0.0087 0.1447 0.1447
Echinococcus multilocularis presenilin 0.0248 0.4179 0.4179
Brugia malayi hypothetical protein 0.0087 0.1447 0.1447
Toxoplasma gondii hypothetical protein 0.0087 0.1447 1
Entamoeba histolytica hypothetical protein 0.0186 0.3129 0.6957
Schistosoma mansoni hypothetical protein 0.0121 0.2024 0.2024
Schistosoma mansoni gamma-secretase subunit aph-1 0.0592 1 1
Brugia malayi Presenilin spe-4 0.0087 0.1447 0.1447
Schistosoma mansoni hypothetical protein 0.049 0.8279 0.8279
Echinococcus granulosus kelch ECH associated protein 1 0.0489 0.8256 0.8256
Echinococcus multilocularis gamma secretase subunit aph 1 0.0592 1 1
Echinococcus granulosus nicalin 0.0044 0.0728 0.0728
Schistosoma mansoni subfamily A22A unassigned peptidase (A22 family) 0.0248 0.4179 0.4179
Brugia malayi Presenilin-like protein At2g29900 0.0087 0.1447 0.1447
Trichomonas vaginalis Clan AD, family A22, presenilin-like aspartic peptidase 0.0248 0.4179 1
Trypanosoma cruzi Aph-1 protein, putative 0.0231 0.3881 0.9136
Echinococcus multilocularis kelch ECH associated protein 1 0.0489 0.8256 0.8256
Brugia malayi Presenilin spe-4 0.0087 0.1447 0.1447
Entamoeba histolytica hypothetical protein 0.0186 0.3129 0.6957
Brugia malayi Presenilin family protein 0.0248 0.4179 0.4179
Leishmania major presenilin-like aspartic peptidase, putative,presenilin-like aspartic peptidase, clan AD, family A22A, putative 0.0248 0.4179 1
Brugia malayi gamma-secretase subunit pen-2 0.0233 0.3921 0.3921
Echinococcus granulosus presenilin enhancer 2 0.0233 0.3921 0.3921
Brugia malayi hypothetical protein 0.0186 0.3129 0.3129
Entamoeba histolytica hypothetical protein 0.0186 0.3129 0.6957
Echinococcus granulosus presenilin 0.0248 0.4179 0.4179
Entamoeba histolytica hypothetical protein 0.0186 0.3129 0.6957
Brugia malayi hypothetical protein 0.0121 0.2024 0.2024
Echinococcus multilocularis Basic leucine zipper (bZIP) transcription 0.0186 0.3129 0.3129
Trichomonas vaginalis Clan AD, family A22, presenilin-like aspartic peptidase 0.0248 0.4179 1
Echinococcus multilocularis Kelch repeat type 1 0.049 0.8279 0.8279
Trypanosoma brucei Aph-1 protein, putative 0.0231 0.3881 0.9136
Brugia malayi hypothetical protein 0.0121 0.2024 0.2024
Brugia malayi Presenilin spe-4 0.0087 0.1447 0.1447
Schistosoma mansoni transcription factor LCR-F1 0.0186 0.3129 0.3129
Trichomonas vaginalis Clan AD, family A22, presenilin-like aspartic peptidase 0.0248 0.4179 1
Entamoeba histolytica presenilin 1 peptidase, putative 0.0248 0.4179 1
Echinococcus multilocularis Nicastrin 0.0121 0.2024 0.2024
Trypanosoma cruzi presenilin-like aspartic peptidase, putative 0.0248 0.4179 1
Echinococcus granulosus Nicastrin 0.0121 0.2024 0.2024
Brugia malayi hypothetical protein 0.0087 0.1447 0.1447
Echinococcus granulosus kelch ECH associated protein 1 like 0.0489 0.8256 0.8256
Loa Loa (eye worm) gamma-secretase subunit aph-1 0.0592 1 1
Echinococcus multilocularis nicalin 0.0044 0.0728 0.0728
Echinococcus granulosus Basic leucine zipper bZIP transcription 0.0186 0.3129 0.3129
Trypanosoma brucei presenilin-like aspartic peptidase, putative 0.0248 0.4179 1
Brugia malayi hypothetical protein 0.0087 0.1447 0.1447
Trypanosoma brucei Presenilin enhancer-2 subunit of gamma secretase, putative 0.007 0.1162 0.1259
Echinococcus granulosus gamma secretase subunit aph 1 0.0592 1 1
Schistosoma mansoni hypothetical protein 0.0186 0.3129 0.3129

Activities

Activity type Activity value Assay description Source Reference
IC50 (binding) = 696 nM Modulation of gamma-secretase in human SK-N-BE(2) cells expressing wild type APP 695 assessed as reduction in amyloid beta 42 level after overnight incubation by sandwich immunoassay ChEMBL. 22650177
Inhibition (binding) Inhibition of gamma-secretase in human SK-N-BE(2) cells expressing wild type APP 695 assessed as reduction in total amyloid beta level up to 10 uM after overnight incubation by sandwich immunoassay ChEMBL. 22650177
Inhibition (binding) Inhibition of beta-secretase in human SK-N-BE(2) cells expressing wild type APP 695 assessed as reduction in total amyloid beta level up to 10 uM after overnight incubation by sandwich immunoassay ChEMBL. 22650177
Inhibition (functional) = 15 % Antialzheimer activity in CD1 mouse assessed as reduction in amyloid beta 42 level in brain at 30 mg/kg, po at 4 hrs by ELISA relative to control ChEMBL. 22650177

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

1 literature reference was collected for this gene.

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