Detailed information for compound 1017917

Basic information

Technical information
  • TDR Targets ID: 1017917
  • Name: (2S)-2-hydroxy-3-methyl-N-[(2S)-1-[[(1S)-3-me thyl-2-oxo-4,5-dihydro-1H-3-benzazepin-1-yl]a mino]-1-oxopropan-2-yl]butanamide
  • MW: 361.435 | Formula: C19H27N3O4
  • H donors: 3 H acceptors: 4 LogP: 1.26 Rotable bonds: 7
    Rule of 5 violations (Lipinski): 1
  • SMILES: O=C([C@@H](NC(=O)[C@H](C(C)C)O)C)N[C@@H]1C(=O)N(C)CCc2c1cccc2
  • InChi: 1S/C19H27N3O4/c1-11(2)16(23)18(25)20-12(3)17(24)21-15-14-8-6-5-7-13(14)9-10-22(4)19(15)26/h5-8,11-12,15-16,23H,9-10H2,1-4H3,(H,20,25)(H,21,24)/t12-,15-,16-/m0/s1
  • InChiKey: PKXWXXPNHIWQHW-RCBQFDQVSA-N  


Substructure search Similarity search

Network

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Synonyms

  • (2S)-2-hydroxy-3-methyl-N-[(1S)-1-methyl-2-[[(1S)-3-methyl-2-oxo-4,5-dihydro-1H-3-benzazepin-1-yl]amino]-2-oxo-ethyl]butanamide
  • (2S)-2-hydroxy-3-methyl-N-[(1S)-1-methyl-2-[[(1S)-3-methyl-2-oxo-4,5-dihydro-1H-3-benzazepin-1-yl]amino]-2-oxoethyl]butanamide
  • (2S)-2-hydroxy-N-[(1S)-2-keto-2-[[(1S)-2-keto-3-methyl-4,5-dihydro-1H-3-benzazepin-1-yl]amino]-1-methyl-ethyl]-3-methyl-butyramide
  • (2S)-2-hydroxy-3-methyl-N-[(2S)-1-[[(1S)-3-methyl-2-oxo-4,5-dihydro-1H-3-benzazepin-1-yl]amino]-1-oxo-propan-2-yl]butanamide

Targets

Known targets for this compound

Species Target name Source Bibliographic reference
Homo sapiens presenilin enhancer gamma secretase subunit References
Homo sapiens APH1B gamma secretase subunit Starlite/ChEMBL References
Homo sapiens nicastrin References
Homo sapiens presenilin 1 References
Homo sapiens presenilin 2 References
Homo sapiens APH1A gamma secretase subunit 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
Echinococcus multilocularis Nicastrin Get druggable targets OG5_131095 All targets in OG5_131095
Loa Loa (eye worm) gamma-secretase subunit pen-2 Get druggable targets OG5_132844 All targets in OG5_132844
Brugia malayi Presenilin family protein 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 Clan AD, family A22, presenilin-like aspartic peptidase Get druggable targets OG5_128959 All targets in OG5_128959
Schistosoma mansoni subfamily A22A unassigned peptidase (A22 family) 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
Echinococcus granulosus 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
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
Loa Loa (eye worm) 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
Brugia malayi hypothetical protein Get druggable targets OG5_131095 All targets in OG5_131095
Brugia malayi 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
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
Brugia malayi gamma-secretase subunit pen-2 Get druggable targets OG5_132844 All targets in OG5_132844
Trichomonas vaginalis Clan AD, family A22, presenilin-like aspartic peptidase 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 gamma secretase subunit aph 1 Get druggable targets OG5_130831 All targets in OG5_130831
Echinococcus multilocularis presenilin Get druggable targets OG5_128959 All targets in OG5_128959
Trypanosoma cruzi 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
Trypanosoma cruzi presenilin-like aspartic peptidase, putative Get druggable targets OG5_128959 All targets in OG5_128959
Schistosoma mansoni hypothetical protein Get druggable targets OG5_131095 All targets in OG5_131095
Schistosoma mansoni gamma-secretase subunit aph-1 Get druggable targets OG5_130831 All targets in OG5_130831
Echinococcus granulosus presenilin 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
Trichomonas vaginalis Clan AD, family A22, presenilin-like aspartic peptidase Get druggable targets OG5_128959 All targets in OG5_128959
Loa Loa (eye worm) hypothetical protein Get druggable targets OG5_131095 All targets in OG5_131095
Entamoeba histolytica presenilin 1 peptidase, 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
Trichomonas vaginalis Nicastrin precursor, putative Get druggable targets OG5_131095 All targets in OG5_131095
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
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
Leishmania donovani presenilin-like aspartic peptidase, putative Get druggable targets OG5_128959 All targets in OG5_128959
Echinococcus granulosus presenilin enhancer 2 Get druggable targets OG5_132844 All targets in OG5_132844
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
Brugia malayi hypothetical protein 0.0121 0.0818 0.0674
Brugia malayi endoprotease bli-4 precursor 0.0408 0.6428 0.6372
Brugia malayi hypothetical protein 0.0121 0.0818 0.0674
Echinococcus multilocularis Nicastrin 0.0121 0.0818 0.0494
Trichomonas vaginalis Clan SB, family S8, subtilisin-like serine peptidase 0.0248 0.3302 1
Brugia malayi Presenilin family protein 0.0248 0.3299 0.3194
Giardia lamblia High cysteine membrane protein Group 2 0.0152 0.142 1
Echinococcus granulosus presenilin 0.0248 0.3299 0.3063
Echinococcus granulosus Nicastrin 0.0121 0.0818 0.0494
Trichomonas vaginalis Clan SB, family S8, subtilisin-like serine peptidase 0.0096 0.0341 0.1032
Trypanosoma brucei presenilin-like aspartic peptidase, putative 0.0248 0.3299 1
Schistosoma mansoni subfamily S8B non-peptidase homologue (S08 family) 0.0096 0.0341 0.0341
Trichomonas vaginalis Clan AD, family A22, presenilin-like aspartic peptidase 0.0248 0.3299 0.9991
Loa Loa (eye worm) hypothetical protein 0.0408 0.6428 0.6372
Echinococcus multilocularis proprotein convertase subtilisin:kexin type 5 0.0248 0.3302 0.3066
Entamoeba histolytica presenilin 1 peptidase, putative 0.0248 0.3299 0.5
Loa Loa (eye worm) proprotein convertase 2 0.0096 0.0341 0.019
Loa Loa (eye worm) gamma-secretase subunit pen-2 0.0233 0.3002 0.2892
Brugia malayi celfurPC protein 0.0329 0.4886 0.4807
Trichomonas vaginalis Clan AD, family A22, presenilin-like aspartic peptidase 0.0248 0.3299 0.9991
Toxoplasma gondii hypothetical protein 0.0087 0.0154 0.5
Trichomonas vaginalis Nicastrin precursor, putative 0.0121 0.0818 0.2477
Trichomonas vaginalis Nicastrin precursor, putative 0.0121 0.0818 0.2477
Brugia malayi neuroendocrine convertase 1 precursor 0.0257 0.3466 0.3365
Trypanosoma cruzi presenilin-like aspartic peptidase, putative 0.0248 0.3299 1
Echinococcus granulosus presenilin enhancer 2 0.0233 0.3002 0.2755
Loa Loa (eye worm) hypothetical protein 0.0121 0.0818 0.0674
Schistosoma mansoni subfamily A22A unassigned peptidase (A22 family) 0.0248 0.3299 0.3299
Schistosoma mansoni subfamily S8B unassigned peptidase (S08 family) 0.0408 0.6428 0.6428
Echinococcus multilocularis Nicastrin 0.0121 0.0818 0.0494
Leishmania major presenilin-like aspartic peptidase, putative,presenilin-like aspartic peptidase, clan AD, family A22A, putative 0.0248 0.3299 0.5
Trichomonas vaginalis Clan SB, family S8, subtilisin-like serine peptidase 0.0096 0.0341 0.1032
Schistosoma mansoni furin-1 (S08 family) 0.0178 0.1925 0.1925
Trypanosoma cruzi presenilin-like aspartic peptidase, putative 0.0248 0.3299 1
Brugia malayi proprotein convertase 2 0.0257 0.3466 0.3365
Echinococcus multilocularis neuroendocrine convertase 2 0.0257 0.3466 0.3236
Trichomonas vaginalis Clan AD, family A22, presenilin-like aspartic peptidase 0.0248 0.3299 0.9991
Echinococcus multilocularis presenilin enhancer 2 0.0233 0.3002 0.2755
Trichomonas vaginalis Clan SB, family S8, subtilisin-like serine peptidase 0.0096 0.0341 0.1032
Echinococcus granulosus gamma secretase subunit aph 1 0.0592 1 1
Trichomonas vaginalis Clan SB, family S8, subtilisin-like serine peptidase 0.0096 0.0341 0.1032
Echinococcus granulosus proprotein convertase subtilisin:kexin type 5 0.0248 0.3302 0.3066
Schistosoma mansoni gamma-secretase subunit aph-1 0.0592 1 1
Trichomonas vaginalis Clan SB, family S8, subtilisin-like serine peptidase 0.0096 0.0341 0.1032
Echinococcus multilocularis 0.0329 0.4886 0.4706
Echinococcus granulosus neuroendocrine convertase 2 0.0257 0.3466 0.3236
Brugia malayi gamma-secretase subunit pen-2 0.0233 0.3002 0.2892
Trichomonas vaginalis Clan SB, family S8, subtilisin-like serine peptidase 0.0096 0.0341 0.1032
Schistosoma mansoni hypothetical protein 0.0121 0.0818 0.0818
Loa Loa (eye worm) endoprotease bli-4 0.0408 0.6428 0.6372
Echinococcus multilocularis gamma secretase subunit aph 1 0.0592 1 1
Echinococcus multilocularis presenilin 0.0248 0.3299 0.3063
Loa Loa (eye worm) hypothetical protein 0.016 0.1584 0.1453
Loa Loa (eye worm) gamma-secretase subunit aph-1 0.0592 1 1
Trichomonas vaginalis Clan SB, family S8, subtilisin-like serine peptidase 0.0248 0.3302 1
Echinococcus granulosus furin 0.0408 0.6428 0.6302

Activities

Activity type Activity value Assay description Source Reference
Activity (binding) Inhibition of gamma-secretase in human SHSY5Y cells expressing human recombinant APP assessed as decrease in Abeta42 level after 24 hrs by DELFIA ChEMBL. 20056541
Activity (binding) Displacement of [3H](S)-5-chloro-N-(3-ethyl-1-hydroxypentan-2-yl)thiophene-2-sulfonamide from gamma secretase in human SH-SY5Y cells after 1 hr ChEMBL. 19443228
Activity (binding) Inhibition of gamma-secretase in human SHSY5Y cells expressing human recombinant APP assessed as increase in Abeta38 level after 24 hrs by DELFIA ChEMBL. 20056541
Activity (functional) = 47 % Reduction in amyloid beta (x to 40) in FVB mouse cortex at 30 mg/kg, po administered as single dose measured at 3 hrs ChEMBL. 23713656
EC50 (binding) = 6.9 Inhibition of gamma-secretase in human SHSY5Y cells expressing human recombinant APP assessed as increase in Abeta38 level after 24 hrs by DELFIA ChEMBL. 20056541
IC50 (ADMET) > 4 Cytotoxicity against human SH-SY5Y cells after 24 hrs by WST1 assay ChEMBL. 20056541
IC50 (binding) = 6.7 Inhibition of gamma-secretase in human SHSY5Y cells expressing human recombinant APP assessed as effect on Abeta40 level after 24 hrs by DELFIA ChEMBL. 20056541
IC50 (binding) = 6.9 Inhibition of gamma-secretase in human SHSY5Y cells expressing human recombinant APP assessed as decrease in Abeta42 level after 24 hrs by DELFIA ChEMBL. 20056541
IC50 (binding) = 7 Inhibition of gamma-secretase in human SHSY5Y cells expressing human recombinant APP assessed as decrease in total Abeta level after 24 hrs by DELFIA ChEMBL. 20056541
IC50 (binding) = 7.4 Inhibition of gamma-secretase in human SHSY5Y cells expressing human recombinant APP assessed as amyloid beta40 formation by ELISA ChEMBL. 20056541
IC50 (binding) = 7.4 Inhibition of gamma-secretase in human SHSY5Y cells expressing human recombinant APP assessed as amyloid beta42 formation by ELISA ChEMBL. 20056541
IC50 (binding) = 3.2 nM Inhibition of partially purified human gamma-secretase-mediated cleavage of notch fusion protein measured after overnight incubation by ELISA ChEMBL. 23713656
IC50 (binding) = 7.9 nM Inhibition of partially purified human gamma-secretase-mediated cleavage of MBP-APPc125Sw fusion protein measured after overnight incubation by ELISA ChEMBL. 23713656
IC50 (binding) = 38 nM Inhibition of gamma secretase-mediated amyloid beta (1 to 40) production in human SH-SY5Y cells ChEMBL. 19694467
IC50 (binding) = 38 nM Displacement of [3H]5-chloro-N-((2S,3R)-5,5,5-trifluoro-1-hydroxy-3-methylpentan-2-yl)thiophene-2-sulfonamide from gamma secretase in human SH-SY5Y cells by competitive binding assay ChEMBL. 19694467
Inhibition (functional) = 38 % Inhibition of gamma secretase-mediated amyloid beta (1 to 40) production in plasma of patient with Alzheimer's disease at 40 mg/kg QD for 6 weeks ChEMBL. 19694467
Inhibition (functional) = 40 % Inhibition of gamma secretase-mediated total amyloid beta production in healthy human plasma at 5 to 50 mg/kg ChEMBL. 19694467
Inhibition (functional) = 52 % Inhibition of gamma secretase-mediated total amyloid beta production in human CSF at 140 mg/kg measured at 12 hrs post-dose ChEMBL. 19694467
Inhibition (functional) = 65 % Inhibition of gamma secretase-mediated total amyloid beta production in plasma of patient with Alzheimer's disease at 140 mg/kg/day, po for 14 weeks ChEMBL. 19694467
Inhibition (functional) = 73 % Inhibition of gamma secretase-mediated total amyloid beta production in human plasma at 140 mg/kg measured at 6 hrs post-dose ChEMBL. 19694467
Ratio IC50 (binding) = 0.41 Selctivity ratio of IC50 for partially purified human gamma-secretase-mediated cleavage of notch fusion protein to IC50 for partially purified human gamma-secretase-mediated cleavage of MBP-APPc125Sw fusion protein ChEMBL. 23713656
T1/2 (ADMET) = 2.5 hr Half life in healthy human at 5 to 50 mg/kg ChEMBL. 19694467

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

4 literature references were collected for this gene.

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