Detailed information for compound 1976034

Basic information

Technical information
  • Name: Unnamed compound
  • MW: 461.455 | Formula: C23H23F4N5O
  • H donors: 2 H acceptors: 2 LogP: 2.67 Rotable bonds: 3
    Rule of 5 violations (Lipinski): 1
  • SMILES: N#Cc1cnc2c(c1)CC[C@@H]2Nc1cc(c(cc1F)F)[C@@]1(C)N=C(N)COC(C1(F)F)(C)C
  • InChi: 1S/C23H23F4N5O/c1-21(2)23(26,27)22(3,32-19(29)11-33-21)14-7-18(16(25)8-15(14)24)31-17-5-4-13-6-12(9-28)10-30-20(13)17/h6-8,10,17,31H,4-5,11H2,1-3H3,(H2,29,32)/t17-,22+/m0/s1
  • InChiKey: ZXPMSLQQIPEYLP-HTAPYJJXSA-N  


Substructure search Similarity search

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 beta-site APP-cleaving enzyme 1 Starlite/ChEMBL No references
Homo sapiens beta-site APP-cleaving enzyme 2 Starlite/ChEMBL No references

Predicted pathogen targets for this compound

By orthology
Species Potential target Known druggable target/s Ortholog Group
Schistosoma japonicum ko:K07747 beta-site APP-cleaving enzyme 2 (memapsin 1) [EC3.4.23.45], putative Get druggable targets OG5_135830 All targets in OG5_135830
Schistosoma mansoni memapsin-2 (A01 family) Get druggable targets OG5_135830 All targets in OG5_135830
By sequence similarity to non orthologous known druggable targets
Species Potential target Known druggable target Length Alignment span Identity
Plasmodium falciparum plasmepsin V beta-site APP-cleaving enzyme 2 518 aa 439 aa 21.9 %
Plasmodium falciparum plasmepsin VII beta-site APP-cleaving enzyme 1 401 aa 352 aa 21.3 %
Obtained from network model

Ranking Plot

Putative Targets List

Species Potential target Raw Global Species
Echinococcus granulosus beta tubulin 0.0546 1 0.5
Schistosoma mansoni tubulin subunit beta 0.0546 1 1
Loa Loa (eye worm) BEN-1 protein 0.0546 1 0.5
Echinococcus granulosus Tubulin beta 2C chain 0.0546 1 0.5
Loa Loa (eye worm) beta-tubulin 0.0546 1 0.5
Echinococcus multilocularis Tubulin beta 2C chain 0.0546 1 0.5
Trypanosoma brucei beta tubulin 0.0546 1 0.5
Leishmania major beta tubulin 0.0546 1 0.5
Toxoplasma gondii beta-1 tubulin, putative 0.0546 1 0.5
Echinococcus granulosus tubulin beta 4A class IVa 0.0546 1 0.5
Leishmania major beta tubulin 0.0546 1 0.5
Entamoeba histolytica tubulin family protein 0.0546 1 0.5
Echinococcus multilocularis Tubulin beta 2C chain 0.0546 1 0.5
Leishmania major beta tubulin 0.0546 1 0.5
Plasmodium falciparum tubulin beta chain 0.0546 1 0.5
Echinococcus granulosus tubulin subunit beta 0.0546 1 0.5
Entamoeba histolytica tubulin family protein 0.0546 1 0.5
Leishmania major beta tubulin 0.0546 1 0.5
Toxoplasma gondii beta-tubulin, putative 0.0546 1 0.5
Loa Loa (eye worm) tubulin beta chain 0.0546 1 0.5
Echinococcus granulosus tubulin beta 1 chain 0.0546 1 0.5
Loa Loa (eye worm) tubulin beta-2A chain 0.0546 1 0.5
Trichomonas vaginalis tubulin gamma chain, putative 0.0546 1 0.5
Echinococcus multilocularis Tubulin beta 2C chain 0.0546 1 0.5
Loa Loa (eye worm) tubulin beta-4 chain 0.0546 1 0.5
Leishmania major beta tubulin 0.0546 1 0.5
Echinococcus multilocularis beta tubulin 0.0546 1 0.5
Trypanosoma brucei beta tubulin 0.0546 1 0.5
Leishmania major beta tubulin 0.0546 1 0.5
Leishmania major beta tubulin 0.0546 1 0.5
Leishmania major beta tubulin 0.0546 1 0.5
Schistosoma mansoni tubulin subunit beta 0.0546 1 1
Echinococcus granulosus Tubulin beta 2C chain 0.0546 1 0.5
Trichomonas vaginalis tubulin, putative 0.0546 1 0.5
Leishmania major beta tubulin 0.0546 1 0.5
Schistosoma mansoni tubulin subunit beta 0.0546 1 1
Trichomonas vaginalis tubulin epsilon chain, putative 0.0546 1 0.5
Echinococcus granulosus Tubulin beta 2C chain 0.0546 1 0.5
Loa Loa (eye worm) BEN-1 protein 0.0546 1 0.5
Echinococcus granulosus Tubulin beta 2C chain 0.0546 1 0.5
Trypanosoma brucei beta tubulin 0.0546 1 0.5
Leishmania major beta tubulin 0.0546 1 0.5
Leishmania major beta tubulin 0.0546 1 0.5
Schistosoma mansoni tubulin subunit beta 0.0546 1 1
Plasmodium vivax tubulin beta chain, putative 0.0546 1 0.5
Toxoplasma gondii beta tubulin 0.0546 1 0.5
Trichomonas vaginalis tubulin alpha chain, putative 0.0546 1 0.5
Echinococcus multilocularis Tubulin beta 2C chain 0.0546 1 0.5
Leishmania major beta tubulin 0.0546 1 0.5
Echinococcus multilocularis tubulin beta 1 chain 0.0546 1 0.5
Leishmania major beta tubulin 0.0546 1 0.5
Loa Loa (eye worm) tubulin beta-1 chain 0.0546 1 0.5
Echinococcus multilocularis beta tubulin 0.0546 1 0.5
Leishmania major beta tubulin 0.0546 1 0.5
Leishmania major beta tubulin 0.0546 1 0.5
Brugia malayi beta-tubulin, identical 0.0546 1 0.5
Trypanosoma cruzi beta tubulin, putative 0.0546 1 0.5
Trypanosoma brucei beta tubulin 0.0546 1 0.5
Trichomonas vaginalis tubulin epsilon chain, putative 0.0546 1 0.5
Echinococcus multilocularis tubulin subunit beta 0.0546 1 0.5
Schistosoma mansoni tubulin subunit beta 0.0546 1 1
Echinococcus multilocularis tubulin, beta 4A class IVa 0.0546 1 0.5
Leishmania major beta tubulin 0.0546 1 0.5
Echinococcus multilocularis Tubulin beta 2C chain 0.0546 1 0.5
Leishmania major beta tubulin 0.0546 1 0.5
Giardia lamblia Beta tubulin 0.0546 1 0.5
Schistosoma mansoni tubulin subunit beta 0.0546 1 1
Echinococcus granulosus beta tubulin 0.0546 1 0.5
Giardia lamblia Beta tubulin 0.0546 1 0.5
Leishmania major beta tubulin 0.0546 1 0.5
Trichomonas vaginalis tubulin beta chain, putative 0.0546 1 0.5
Giardia lamblia Beta tubulin 0.0546 1 0.5
Echinococcus granulosus Tubulin beta 2C chain 0.0546 1 0.5

Activities

Activity type Activity value Assay description Source Reference
IC50 (binding) = 170 nM BindingDB_Patents: Immunofluorescence Resonance Energy Transfer (FRET) Assay. The FRET assay was performed essentially as described in Gruninger-Leitch et al., Journal of Biological Chemistry (2002) 277(7) 4687-93 (Substrate and inhibitor profile of BACE (beta-secretase) and comparison with other mammalian aspartic proteases). In summary, a peptide is designed that is cleaved by the protease. The peptide is labelled with dabcyl at the N terminus and Lucifer Yellow at the C-terminus, such that for an intact peptide the Lucifer Yellow fluorescence is quenched by the dabcyl. When the peptide is cut by BACE2, the quenching is removed and a fluorescent signal is generated. The assay was performed as described in Grueninger et al. 2002 at pH 4.5 using a substrate concentration of 5 uM. A FRET peptide based on the TMEM27 sequence was devised. dabcyl-QTLEFLKIPS-LucY (SEQ ID NO: 1). BACE2 had a high activity against this sequence, which is unrelated to the known APP-based substrates. Conversely, BACE1 had insignificant activity against this peptide. ChEMBL. No reference
IC50 (binding) = 1900 nM BindingDB_Patents: Immunofluorescence Resonance Energy Transfer (FRET) Assay. The FRET assay was performed essentially as described in Gruninger-Leitch et al., Journal of Biological Chemistry (2002) 277(7) 4687-93 (Substrate and inhibitor profile of BACE (beta-secretase) and comparison with other mammalian aspartic proteases). In summary, a peptide is designed that is cleaved by the protease. The peptide is labelled with dabcyl at the N terminus and Lucifer Yellow at the C-terminus, such that for an intact peptide the Lucifer Yellow fluorescence is quenched by the dabcyl. When the peptide is cut by BACE2, the quenching is removed and a fluorescent signal is generated. The assay was performed as described in Grueninger et al. 2002 at pH 4.5 using a substrate concentration of 5 µM. A FRET peptide based on the TMEM27 sequence was devised. dabcyl-QTLEFLKIPS-LucY (SEQ ID NO: 1). BACE2 had a high activity against this sequence, which is unrelated to the known APP-based substrates. Conversely, BACE1 had insignificant activity against this peptide. 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:

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

No literature references available for this target.

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