Detailed information for compound 141804

Basic information

Technical information
  • TDR Targets ID: 141804
  • Name: 1-(4-chlorophenyl)-2-[3-(5,6-dihydrobenzo[b][ 1]benzazepin-11-yl)propyl-methylamino]ethanon e
  • MW: 418.958 | Formula: C26H27ClN2O
  • H donors: 0 H acceptors: 1 LogP: 6.33 Rotable bonds: 7
    Rule of 5 violations (Lipinski): 1
  • SMILES: CN(CC(=O)c1ccc(cc1)Cl)CCCN1c2ccccc2CCc2c1cccc2
  • InChi: 1S/C26H27ClN2O/c1-28(19-26(30)22-13-15-23(27)16-14-22)17-6-18-29-24-9-4-2-7-20(24)11-12-21-8-3-5-10-25(21)29/h2-5,7-10,13-16H,6,11-12,17-19H2,1H3
  • InChiKey: SAPNXPWPAUFAJU-UHFFFAOYSA-N  


Substructure search Similarity search

Network

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Synonyms

  • 1-(4-chlorophenyl)-2-[3-(5,6-dihydrobenzo[b][1]benzazepin-11-yl)propyl-methyl-amino]ethanone
  • Lofepramine
  • 23047-25-8
  • 4'-chloro-2-((3-(10,11-dihydro-5H-dibenz(b,f)azepin5-yl)propyl)methylamino)acetophenone
  • Ethanone, 1-(4-chlorophenyl)-2-[[3-(10,11-dihydro-5H-dibenz[b,f]azepin-5-yl)propyl]methylamino]-
  • 4'-Chlor-2-((3-(10,11-dihydro-5H-dibenz(b,f)azepin-5-yl)propyl)methylamino)acetophenon
  • Acetophenone, 4'-chloro-2-((3-(10,11-dihydro-5H-dibenz(b,f)azepin5-yl)propyl)methylamino)-
  • 1-(4-chlorophenyl)-2-{[3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl]methylamino}ethanone
  • DB 2182
  • EINECS 245-396-8
  • Ethanone, 1-(4-chlorophenyl)-2-((3-(10,11-dihydro-5H-dibenz(b,f)azepin-5-yl)propyl)methylamino)-
  • HSDB 7184
  • Lofepramina [INN-Spanish]
  • Lofepraminum [INN-Latin]
  • Lopramine
  • 1-(4-chlorophenyl)-2-{[3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl](methyl)amino}ethanone
  • CHEBI:47782

Targets

Known targets for this compound

Species Target name Source Bibliographic reference
Rattus norvegicus Peripheral myelin protein 22 Starlite/ChEMBL No references
Homo sapiens euchromatic histone-lysine N-methyltransferase 2 Starlite/ChEMBL No references
Bacillus subtilis 4'-phosphopantetheinyl transferase ffp Starlite/ChEMBL No references

Predicted pathogen targets for this compound

By orthology
Species Potential target Known druggable target/s Ortholog Group
Schistosoma mansoni aminoadipate-semialdehyde dehydrogenase Get druggable targets OG5_129301 All targets in OG5_129301
Onchocerca volvulus Get druggable targets OG5_131470 All targets in OG5_131470
Schistosoma japonicum ko:K00142 aminoadipate-semialdehyde dehydrogenase [EC1.2.1.31], putative Get druggable targets OG5_129301 All targets in OG5_129301
Onchocerca volvulus Get druggable targets OG5_129301 All targets in OG5_129301
Brugia malayi Pre-SET motif family protein Get druggable targets OG5_131470 All targets in OG5_131470
Cryptosporidium hominis proteinx0005 Get druggable targets OG5_129301 All targets in OG5_129301
Loa Loa (eye worm) hypothetical protein Get druggable targets OG5_129301 All targets in OG5_129301
Echinococcus granulosus L aminoadipate semialdehyde Get druggable targets OG5_129301 All targets in OG5_129301
Brugia malayi aminoadipate-semialdehyde dehydrogenase-phosphopantetheinyl transferase Get druggable targets OG5_129301 All targets in OG5_129301
Loa Loa (eye worm) pre-SET domain-containing protein family protein Get druggable targets OG5_131470 All targets in OG5_131470
Cryptosporidium parvum phosphopantetheinyl transferase Get druggable targets OG5_129301 All targets in OG5_129301
Echinococcus multilocularis L aminoadipate semialdehyde Get druggable targets OG5_129301 All targets in OG5_129301
Trichomonas vaginalis set domain proteins, putative Get druggable targets OG5_131470 All targets in OG5_131470
Schistosoma japonicum expressed protein Get druggable targets OG5_129301 All targets in OG5_129301
By sequence similarity to non orthologous known druggable targets
Species Potential target Known druggable target Length Alignment span Identity
Candida albicans aminoadipate-semialdehyde dehydrogenase small subunit 4'-phosphopantetheinyl transferase ffp   224 aa 183 aa 27.3 %
Trichomonas vaginalis conserved hypothetical protein 4'-phosphopantetheinyl transferase ffp   224 aa 197 aa 22.3 %
Entamoeba histolytica hypothetical protein 4'-phosphopantetheinyl transferase ffp   224 aa 198 aa 28.3 %
Onchocerca volvulus 4'-phosphopantetheinyl transferase ffp   224 aa 186 aa 26.3 %
Brugia malayi hypothetical protein Peripheral myelin protein 22   160 aa 129 aa 25.6 %
Candida albicans aminoadipate-semialdehyde dehydrogenase small subunit 4'-phosphopantetheinyl transferase ffp   224 aa 183 aa 27.3 %
Obtained from network model

Ranking Plot

Putative Targets List

Species Potential target Raw Global Species
Toxoplasma gondii histone lysine methyltransferase SET/SUV39 0.0036 0 0.5
Loa Loa (eye worm) hypothetical protein 0.0251 0.8617 0.8978
Brugia malayi hypothetical protein 0.008 0.1743 0.2025
Echinococcus multilocularis Basic leucine zipper (bZIP) transcription factor 0.0101 0.2614 0.2801
Brugia malayi aminoadipate-semialdehyde dehydrogenase-phosphopantetheinyl transferase 0.01 0.2574 0.2989
Entamoeba histolytica hypothetical protein 0.0043 0.0296 0.5
Trichomonas vaginalis set domain proteins, putative 0.0286 1 0.5
Echinococcus multilocularis n acetylated alpha linked acidic dipeptidase 2 0.0269 0.9336 1
Onchocerca volvulus 0.008 0.1743 0.1743
Plasmodium vivax SET domain protein, putative 0.0036 0 0.5
Schistosoma mansoni jun-related protein 0.0082 0.1855 0.33
Entamoeba histolytica hypothetical protein 0.0043 0.0296 0.5
Schistosoma mansoni hypothetical protein 0.0082 0.1855 0.33
Schistosoma mansoni NAALADASE L peptidase (M28 family) 0.0177 0.5621 1
Loa Loa (eye worm) hypothetical protein 0.0276 0.9598 1
Brugia malayi Pre-SET motif family protein 0.0251 0.8611 1
Loa Loa (eye worm) pre-SET domain-containing protein family protein 0.0251 0.8611 0.8971
Brugia malayi bZIP transcription factor family protein 0.0101 0.2614 0.3036
Echinococcus granulosus L aminoadipate semialdehyde 0.01 0.2574 0.9846
Echinococcus multilocularis jun protein 0.0101 0.2614 0.2801
Echinococcus multilocularis L aminoadipate semialdehyde 0.01 0.2574 0.2757
Schistosoma mansoni hypothetical protein 0.0043 0.0296 0.0526
Entamoeba histolytica hypothetical protein 0.0043 0.0296 0.5
Onchocerca volvulus 0.01 0.2574 0.2574
Schistosoma mansoni hypothetical protein 0.0062 0.1056 0.1879
Loa Loa (eye worm) hypothetical protein 0.0183 0.5883 0.613
Loa Loa (eye worm) hypothetical protein 0.01 0.2574 0.2682
Echinococcus multilocularis Basic leucine zipper (bZIP) transcription 0.0043 0.0296 0.0317
Entamoeba histolytica hypothetical protein 0.0043 0.0296 0.5
Echinococcus granulosus jun protein 0.0101 0.2614 1
Brugia malayi hypothetical protein 0.0043 0.0296 0.0344
Loa Loa (eye worm) hypothetical protein 0.0099 0.2503 0.2608
Echinococcus granulosus Basic leucine zipper bZIP transcription 0.0043 0.0296 0.1132
Echinococcus granulosus Basic leucine zipper bZIP transcription factor 0.0101 0.2614 1
Schistosoma mansoni transcription factor LCR-F1 0.0043 0.0296 0.0526
Schistosoma mansoni aminoadipate-semialdehyde dehydrogenase 0.01 0.2574 0.458

Activities

Activity type Activity value Assay description Source Reference
Activity (binding) = 90.5 % Inhibition of ASM in human H4 cells assessed as residual activity at 10 uM ChEMBL. 18027916
Activity (binding) = 90.5 % Inhibition of ASM in human H4 cells assessed as residual activity at 10 uM ChEMBL. 18027916
delta logD (ADMET) = -0.32 Delta logD (logD6.5 - logD7.4) ChEMBL. 10891117
F (ADMET) <= 20 % Oral bioavailability in human ChEMBL. 10891117
IC50 (functional) Antimicrobial activity against Leishmania major ChEMBL. 20185316
IC50 (functional) Antimicrobial activity against Entamoeba histolytica ChEMBL. 20185316
IC50 (functional) Antimicrobial activity against Leishmania mexicana ChEMBL. 20185316
IC50 (functional) Antimicrobial activity against Leishmania infantum ChEMBL. 20185316
IC50 (functional) Antimicrobial activity against Trypanosoma cruzi ChEMBL. 20185316
IC50 (functional) Antimicrobial activity against Cryptosporidium parvum ChEMBL. 20185316
IC50 (functional) Antimicrobial activity against Trichomonas vaginalis ChEMBL. 20185316
IC50 (functional) Antimicrobial activity against Trypanosoma brucei brucei ChEMBL. 20185316
IC50 (functional) Antimicrobial activity against Toxoplasma gondii ChEMBL. 20185316
IC50 (functional) Antimicrobial activity against Trypanosoma brucei ChEMBL. 20185316
IC50 (functional) Antimicrobial activity against Plasmodium falciparum ChEMBL. 20185316
IC50 (functional) Antimicrobial activity against Trypanosoma brucei rhodesiense ChEMBL. 20185316
IC50 (functional) Antimicrobial activity against Leishmania donovani ChEMBL. 20185316
IC50 (binding) > 20000 nM BindingDB_Patents: Kinase Assay. Approximately 5-20 µg of purified GST-RET proteins were incubated with 1 mM ATP in 20 µL kinase buffer (10 mM Tris-HCl, 5 mM MgCl2, pH 7.4), at 30° C. for 30 minutes. The kinase reactions were terminated by boiling the samples in SDS-PAGE sample buffer. Samples were resolved on 10% acrylamide gels by SDS-PAGE followed by Western blotting. Phosphorylation was detected using a pan-phosphotyrosine pY99 antibody (available from Santa Cruz Biotechnology) or RET phospho-specific antibody (pY905, available from Cell Signaling, Beverly, Mass., USA). ChEMBL. No reference
IC50 (binding) > 20000 nM BindingDB_Patents: Kinase Assay. Approximately 5-20 µg of purified GST-RET proteins were incubated with 1 mM ATP in 20 µL kinase buffer (10 mM Tris-HCl, 5 mM MgCl2, pH 7.4), at 30° C. for 30 minutes. The kinase reactions were terminated by boiling the samples in SDS-PAGE sample buffer. Samples were resolved on 10% acrylamide gels by SDS-PAGE followed by Western blotting. Phosphorylation was detected using a pan-phosphotyrosine pY99 antibody (available from Santa Cruz Biotechnology) or RET phospho-specific antibody (pY905, available from Cell Signaling, Beverly, Mass., USA). ChEMBL. No reference
logD (ADMET) = 4.58 Partition coefficient (logD6.5) ChEMBL. 10891117
pKa = 6.7 Ionization constant (pKa) ChEMBL. 10891117
Potency (functional) 1.2589 uM PUBCHEM_BIOASSAY: qHTS Assay for Inhibitors of Histone Lysine Methyltransferase G9a. (Class of assay: confirmatory) [Related pubchem assays (depositor defined):AID504404] ChEMBL. No reference
Potency (functional) 14.3818 uM PUBCHEM_BIOASSAY: S16 Schwann cell PMP22 intronic element firefly luciferase assay. (Class of assay: confirmatory) ChEMBL. No reference
Potency (functional) 15.1014 uM PUBCHEM_BIOASSAY: Primary qHTS for delayed death inhibitors of the malarial parasite plastid, 96 hour incubation. (Class of assay: confirmatory) [Related pubchem assays (depositor defined):AID488745, AID488752, AID488774, AID504848, AID504850] ChEMBL. No reference
Potency (functional) = 15.8489 um PUBCHEM_BIOASSAY: qHTS Assay for Inhibitors of Bacillus subtilis Sfp phosphopantetheinyl transferase (PPTase). (Class of assay: confirmatory) ChEMBL. No reference
Potency (functional) 33.4983 uM PubChem BioAssay. A quantitative high throughput screen for small molecules that induce DNA re-replication in MCF 10a normal breast cells. (Class of assay: confirmatory) ChEMBL. No reference
Potency (functional) 33.4983 uM PubChem BioAssay. A quantitative high throughput screen for small molecules that induce DNA re-replication in SW480 colon adenocarcinoma cells. (Class of assay: confirmatory) ChEMBL. No reference
Potency (functional) 35.4813 uM PUBCHEM_BIOASSAY: Inhibitors of the vitamin D receptor (VDR): qHTS. (Class of assay: confirmatory) [Related pubchem assays (depositor defined):AID504855] ChEMBL. No reference
Potency (functional) 35.4813 uM PUBCHEM_BIOASSAY: Inhibitors of USP1/UAF1: Pilot qHTS. (Class of assay: confirmatory) [Related pubchem assays (depositor defined):AID504878] ChEMBL. No reference
Potency (functional) = 37.2898 um PUBCHEM_BIOASSAY: Confirmation qHTS Assay for Inhibitors of Bacillus subtilis Sfp phosphopantetheinyl transferase (PPTase). (Class of assay: confirmatory) [Related pubchem assays: 1490 (qHTS Assay for Inhibitors of Bacillus subtilis Sfp phosphopantetheinyl transferase (PPTase)), 1819 (Probe Development Summary of Inhibitors of Bacillus subtilis Sfp phosphopantetheinyl transferase (PPTase))] ChEMBL. No reference
Potency (functional) 39.8107 uM PUBCHEM_BIOASSAY: Inhibitors of the vitamin D receptor (VDR): qHTS. (Class of assay: confirmatory) [Related pubchem assays (depositor defined):AID504855] ChEMBL. No reference
Potency (binding) = 44.6684 um PUBCHEM_BIOASSAY: qHTS Assay for Inhibitors of Tyrosyl-DNA Phosphodiesterase (TDP1). (Class of assay: confirmatory) ChEMBL. No reference
Potency (functional) = 50.1187 um PUBCHEM_BIOASSAY: qHTS Assay for Inhibitors of Bacillus subtilis Sfp phosphopantetheinyl transferase (PPTase). (Class of assay: confirmatory) ChEMBL. No reference

Phenotypes

Whole-cell/tissue/organism interactions

Species name Source Reference Is orphan
Plasmodium falciparum ChEMBL23

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

2 literature references were collected for this gene.

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