Detailed information for compound 1950587

Basic information

Technical information
  • Name: Unnamed compound
  • MW: 434.408 | Formula: C22H21F3N2O4
  • H donors: 1 H acceptors: 0 LogP: 3.66 Rotable bonds: 3
    Rule of 5 violations (Lipinski): 1
  • SMILES: NC1=NC2(CO1)c1cc(ccc1OC(C12COC1)(C)C)c1ccccc1OC(F)(F)F
  • InChi: 1S/C22H21F3N2O4/c1-19(2)20(10-28-11-20)21(12-29-18(26)27-21)15-9-13(7-8-17(15)30-19)14-5-3-4-6-16(14)31-22(23,24)25/h3-9H,10-12H2,1-2H3,(H2,26,27)
  • InChiKey: DXUBDEWFIYBFBX-UHFFFAOYSA-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

Predicted pathogen targets for this compound

By orthology
Species Potential target Known druggable target/s Ortholog Group
Schistosoma mansoni memapsin-2 (A01 family) Get druggable targets OG5_135830 All targets in OG5_135830
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
By sequence similarity to non orthologous known druggable targets
Species Potential target Known druggable target Length Alignment span Identity
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 protein farnesyltransferase subunit beta 0.0626 0.7363 0.5
Trichomonas vaginalis geranylgeranyl transferase type I beta subunit, putative 0.0626 0.7363 0.5
Brugia malayi Prenyltransferase and squalene oxidase repeat family protein 0.0626 0.7363 0.5
Toxoplasma gondii prenyltransferase and squalene oxidase repeat-containing protein 0.0626 0.7363 0.5
Trypanosoma brucei lanosterol synthase 0.0687 1 1
Plasmodium vivax farnesyltransferase beta subunit, putative 0.0626 0.7363 1
Schistosoma mansoni protein farnesyltransferase subunit beta 0.0626 0.7363 1
Trypanosoma cruzi lanosterol synthase, putative 0.0687 1 1
Leishmania major farnesyltransferase beta subunit 0.0626 0.7363 1
Trichomonas vaginalis geranylgeranyl transferase type II beta subunit, putative 0.0626 0.7363 0.5
Trichomonas vaginalis geranylgeranyl transferase type II beta subunit, putative 0.0626 0.7363 0.5
Entamoeba histolytica protein farnesyltransferase beta subunit, putative 0.0626 0.7363 0.5
Trypanosoma cruzi lanosterol synthase, putative 0.0687 1 1
Plasmodium falciparum protein farnesyltransferase subunit beta 0.0626 0.7363 0.5
Trichomonas vaginalis geranylgeranyl transferase type beta subunit, putative 0.0626 0.7363 0.5
Trichomonas vaginalis type I geranylgeranyltransferase beta subunit, putative 0.0626 0.7363 0.5
Giardia lamblia Prenyltransferase 0.0626 0.7363 0.5
Loa Loa (eye worm) prenyltransferase and squalene oxidase repeat family protein 0.0626 0.7363 0.5
Trichomonas vaginalis geranylgeranyl transferase type II beta subunit, putative 0.0626 0.7363 0.5
Echinococcus multilocularis protein farnesyltransferase subunit beta 0.0626 0.7363 0.5

Activities

Activity type Activity value Assay description Source Reference
IC50 (binding) = 2720 nM BindingDB_Patents: Time Resolved Fluorescence Resonance Energy Transfer (TR-FRET) Assay. Potency of compounds were also measured using another fluorogenic substrate, TruPoint BACE1 Substrate Eu-CEVNLDAEFK-QSY 7 (SEQ ID NO:3) (AD0258, PerkinElmer, Boston Mass.). This substrate also has Swedish variant amino acids at the ß-secretase cleavage site, with a fluorescent europium (Eu) chelate coupled to one end and a quencher of europium fluorescence (QSY7) coupled to the other end via lysine. If the sample contains BACE1 activity, the Eu chelate and the quencher will be separated as the substrate is cleaved. The Eu-signal increases and it can be measured by time-resolved fluorometry, EnVision, 30 minutes after the substrate (final concentration 300 nM) was added. ChEMBL. No reference
IC50 (binding) = 2720 nM Time Resolved Fluorescence Resonance Energy Transfer (TR-FRET) Assay BINDINGDB. No reference
IC50 (binding) = 2720 nM BindingDB_Patents: Time Resolved Fluorescence Resonance Energy Transfer (TR-FRET) Assay. Potency of compounds were also measured using another fluorogenic substrate, TruPoint BACE1 Substrate Eu-CEVNLDAEFK-QSY 7 (SEQ ID NO:3) (AD0258, PerkinElmer, Boston Mass.). This substrate also has Swedish variant amino acids at the ß-secretase cleavage site, with a fluorescent europium (Eu) chelate coupled to one end and a quencher of europium fluorescence (QSY7) coupled to the other end via lysine. If the sample contains BACE1 activity, the Eu chelate and the quencher will be separated as the substrate is cleaved. The Eu-signal increases and it can be measured by time-resolved fluorometry, EnVision, 30 minutes after the substrate (final concentration 300 nM) was added. ChEMBL. No reference
IC50 (binding) = 2820 nM BindingDB_Patents: Fluorescence Resonance Energy Transfer (FRET) Assay. Potency of test compounds were determined by measurement of their inhibition of BACE1 activity toward a fluorescent substrate. Experiments were performed by reference to the procedure as described in Ermolieff, et al. (Biochemistry 39:12450-12456 (2000), the teachings of which are incorporated hereby in their entirety). Briefly, the recombinant protease unit of BACE1 was prepared from E. coli expression as inclusion bodies, refolded, and purified as described in Lin, et al., (Proc. Nat. Acad. Sci. 97:1456-1460 (2000)). Fluorogenic substrate, MCA-SEVNLDAEFK(DNP)-NH2 (SEQ ID NO:1) was purchased. (M-2485, Bachem Americas, Torrance, Calif.). The substrate was derived from 10 amino acids of the human amyloid precursor protein (APP), with the Swedish variant amino acids at the beta-secretase cleavage site. The terminal amino acid was modified from arginine to lysine to facilitate derivatization with a functional group for detection by autofluorescence. ChEMBL. No reference
IC50 (binding) = 2820 nM BindingDB_Patents: Fluorescence Resonance Energy Transfer (FRET) Assay. Potency of test compounds were determined by measurement of their inhibition of BACE1 activity toward a fluorescent substrate. Experiments were performed by reference to the procedure as described in Ermolieff, et al. (Biochemistry 39:12450-12456 (2000), the teachings of which are incorporated hereby in their entirety). Briefly, the recombinant protease unit of BACE1 was prepared from E. coli expression as inclusion bodies, refolded, and purified as described in Lin, et al., (Proc. Nat. Acad. Sci. 97:1456-1460 (2000)). Fluorogenic substrate, MCA-SEVNLDAEFK(DNP)-NH2 (SEQ ID NO:1) was purchased. (M-2485, Bachem Americas, Torrance, Calif.). The substrate was derived from 10 amino acids of the human amyloid precursor protein (APP), with the Swedish variant amino acids at the beta-secretase cleavage site. The terminal amino acid was modified from arginine to lysine to facilitate derivatization with a functional group for detection by autofluorescence. ChEMBL. No reference
IC50 (binding) = 2820 nM Fluorescence Resonance Energy Transfer (FRET) Assay BINDINGDB. 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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