Detailed information for compound 460254

Basic information

Technical information
  • TDR Targets ID: 460254
  • Name: N-[(2S)-1-(3,5-difluorophenyl)-3-hydroxypropa n-2-yl]-2-[[(1S,2S)-2-methylcyclopropyl]methy lamino]-6-[methyl(methylsulfonyl)amino]pyridi ne-4-carboxamide
  • MW: 482.544 | Formula: C22H28F2N4O4S
  • H donors: 3 H acceptors: 5 LogP: 2.65 Rotable bonds: 11
    Rule of 5 violations (Lipinski): 1
  • SMILES: OC[C@@H](NC(=O)c1cc(NC[C@H]2C[C@@H]2C)nc(c1)N(S(=O)(=O)C)C)Cc1cc(F)cc(c1)F
  • InChi: 1S/C22H28F2N4O4S/c1-13-4-16(13)11-25-20-8-15(9-21(27-20)28(2)33(3,31)32)22(30)26-19(12-29)7-14-5-17(23)10-18(24)6-14/h5-6,8-10,13,16,19,29H,4,7,11-12H2,1-3H3,(H,25,27)(H,26,30)/t13-,16+,19-/m0/s1
  • InChiKey: WOZUPVNRNGMNND-CRFBAAHOSA-N  


Substructure search Similarity search

Network

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Synonyms

  • N-[(1S)-1-[(3,5-difluorophenyl)methyl]-2-hydroxy-ethyl]-2-[[(1S,2S)-2-methylcyclopropyl]methylamino]-6-[methyl(methylsulfonyl)amino]pyridine-4-carboxamide
  • N-[(1S)-1-[(3,5-difluorophenyl)methyl]-2-hydroxyethyl]-2-[[(1S,2S)-2-methylcyclopropyl]methylamino]-6-[methyl(methylsulfonyl)amino]-4-pyridinecarboxamide
  • N-[(2S)-1-(3,5-difluorophenyl)-3-hydroxy-propan-2-yl]-2-[[(1S,2S)-2-methylcyclopropyl]methylamino]-6-[methyl(methylsulfonyl)amino]pyridine-4-carboxamide
  • N-[(1S)-1-(3,5-difluorobenzyl)-2-hydroxy-ethyl]-2-[mesyl(methyl)amino]-6-[[(1S,2S)-2-methylcyclopropyl]methylamino]isonicotinamide
  • N-[(2S)-1-(3,5-difluorophenyl)-3-hydroxypropan-2-yl]-2-[[(1S,2S)-2-methylcyclopropyl]methylamino]-6-(methyl-methylsulfonylamino)pyridine-4-carboxamide
  • N-[(1S)-1-[(3,5-difluorophenyl)methyl]-2-hydroxy-ethyl]-2-[[(1S,2S)-2-methylcyclopropyl]methylamino]-6-(methyl-methylsulfonyl-amino)pyridine-4-carboxamide
  • N-[(1S)-1-[(3,5-difluorophenyl)methyl]-2-hydroxyethyl]-2-[[(1S,2S)-2-methylcyclopropyl]methylamino]-6-(methyl-methylsulfonylamino)-4-pyridinecarboxamide
  • N-[(1S)-1-(3,5-difluorobenzyl)-2-hydroxy-ethyl]-2-(mesyl-methyl-amino)-6-[[(1S,2S)-2-methylcyclopropyl]methylamino]isonicotinamide
  • N-[(2S)-1-(3,5-difluorophenyl)-3-hydroxy-propan-2-yl]-2-[[(1S,2S)-2-methylcyclopropyl]methylamino]-6-(methyl-methylsulfonyl-amino)pyridine-4-carboxamide

Targets

Known targets for this compound

Species Target name Source Bibliographic reference
Homo sapiens beta-site APP-cleaving enzyme 1 Starlite/ChEMBL 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
Mycobacterium ulcerans thioesterase 0.0099 0.1519 0.506
Plasmodium vivax 3-oxoacyl-[acyl-carrier-protein] synthase i/ii, putative 0.003 0.0126 1
Loa Loa (eye worm) hypothetical protein 0.0189 0.3322 0.5675
Echinococcus granulosus Basic leucine zipper bZIP transcription 0.0036 0.0255 0.0256
Mycobacterium tuberculosis Polyketide synthetase MbtD (polyketide synthase) 0.0037 0.0261 0.0545
Loa Loa (eye worm) AMP-binding enzyme family protein 0.0111 0.176 0.2915
Plasmodium falciparum 3-oxoacyl-acyl-carrier protein synthase I/II 0.003 0.0126 1
Loa Loa (eye worm) hypothetical protein 0.0056 0.0644 0.0942
Loa Loa (eye worm) latrophilin receptor protein 2 0.0048 0.0494 0.0678
Mycobacterium ulcerans polyketide synthase Pks9 0.0068 0.0885 0.2759
Echinococcus multilocularis Basic leucine zipper (bZIP) transcription 0.0036 0.0255 0.0256
Brugia malayi hypothetical protein 0.0036 0.0255 0.0389
Mycobacterium tuberculosis Probable polyketide synthase Pks5 0.0115 0.1844 0.6264
Loa Loa (eye worm) acyl carrier protein 0.0055 0.0626 0.091
Mycobacterium tuberculosis Phenolpthiocerol synthesis type-I polyketide synthase PpsD 0.0108 0.1695 0.5727
Brugia malayi Latrophilin receptor protein 2 0.0048 0.0494 0.1029
Echinococcus granulosus guanine nucleotide binding protein Gs subunit 0.0046 0.0454 0.0606
Leishmania major hypothetical protein, conserved 0.0036 0.0246 1
Echinococcus multilocularis guanine nucleotide binding protein G(s) subunit 0.0046 0.0454 0.0606
Loa Loa (eye worm) hypothetical protein 0.0104 0.1618 0.2664
Mycobacterium tuberculosis Probable polyketide synthase Pks15 0.0048 0.0493 0.1383
Schistosoma mansoni hypothetical protein 0.0048 0.0494 0.0388
Schistosoma mansoni hypothetical protein 0.031 0.5769 0.5722
Schistosoma mansoni hypothetical protein 0.0104 0.1618 0.1524
Mycobacterium tuberculosis Probable membrane bound polyketide synthase Pks6 0.0167 0.2878 1
Schistosoma mansoni Guanine nucleotide-binding protein G(s) subunit alpha (Adenylate cyclase-stimulating G alpha protein) 0.0046 0.0454 0.0347
Mycobacterium leprae PHENOLPTHIOCEROL SYNTHESIS TYPE-I POLYKETIDE SYNTHASE PPSD 0.0108 0.1695 0.5453
Chlamydia trachomatis 3-oxoacyl-ACP synthase 0.003 0.0126 0.5
Schistosoma mansoni methyltransferase-related 0.0036 0.0246 0.0137
Mycobacterium ulcerans phenolpthiocerol synthesis type-I polyketide synthase PpsD 0.0108 0.1695 0.5702
Mycobacterium tuberculosis Polyketide synthetase MbtC (polyketide synthase) 0.003 0.0126 0.0058
Mycobacterium tuberculosis Probable thioesterase TesA 0.0099 0.1519 0.5088
Mycobacterium ulcerans Type I modular polyketide synthase 0.0108 0.1695 0.5702
Entamoeba histolytica hypothetical protein 0.0036 0.0255 1
Schistosoma mansoni hypothetical protein 0.0048 0.0494 0.0388
Trypanosoma cruzi beta-ketoacyl synthase family protein, putative 0.003 0.0126 1
Mycobacterium ulcerans polyketide synthase 0.0115 0.1844 0.6242
Mycobacterium tuberculosis Probable polyketide synthase Pks1 0.0085 0.1244 0.4095
Mycobacterium leprae PHENOLPTHIOCEROL SYNTHESIS TYPE-I POLYKETIDE SYNTHASE PPSA 0.0108 0.1695 0.5453
Brugia malayi RNA, U transporter 1 0.0083 0.1189 0.2894
Leishmania major beta-ketoacyl synthase family protein, putative,3-oxoacyl-acyl carrier protein synthase ii, putative 0.003 0.0126 0.5119
Echinococcus multilocularis snurportin 1 0.031 0.5769 1
Echinococcus granulosus 3 oxoacyl acyl carrier protein synthase 0.003 0.0126 0.0027
Brugia malayi GTP-binding regulatory protein Gs alpha-S chain, putative 0.0046 0.0454 0.092
Trichomonas vaginalis conserved hypothetical protein 0.0036 0.0246 1
Schistosoma mansoni transcription factor LCR-F1 0.0036 0.0255 0.0146
Mycobacterium ulcerans phenolpthiocerol synthesis type-I polyketide synthase PpsC 0.0115 0.1844 0.6242
Echinococcus granulosus GPCR family 2 0.0048 0.0494 0.0678
Entamoeba histolytica hypothetical protein 0.0036 0.0255 1
Trypanosoma cruzi beta-ketoacyl synthase family protein, putative 0.003 0.0126 1
Echinococcus multilocularis 3 oxoacyl (acyl carrier protein) synthase 0.003 0.0126 0.0027
Giardia lamblia Methyltransferase like 2 0.0036 0.0246 0.5
Mycobacterium tuberculosis Phenolpthiocerol synthesis type-I polyketide synthase PpsC 0.0108 0.1695 0.5727
Mycobacterium tuberculosis Phenyloxazoline synthase MbtB (phenyloxazoline synthetase) 0.0111 0.176 0.5961
Toxoplasma gondii AMP-binding enzyme domain-containing protein 0.006 0.0734 0.3599
Echinococcus granulosus guanine nucleotide binding protein Gs subunit 0.0046 0.0454 0.0606
Loa Loa (eye worm) beta-ketoacyl synthase domain-containing protein 0.003 0.0126 0.0027
Loa Loa (eye worm) pigment dispersing factor receptor c 0.0152 0.2586 0.4375
Mycobacterium tuberculosis Conserved protein 0.0036 0.0246 0.0492
Mycobacterium tuberculosis Probable fatty acid synthase Fas (fatty acid synthetase) 0.0037 0.0277 0.0603
Toxoplasma gondii 3-oxoacyl-acyl-carrier protein synthase I/II, putative 0.003 0.0126 0.0089
Brugia malayi calcium-independent alpha-latrotoxin receptor 2, putative 0.0048 0.0494 0.1029
Brugia malayi Methyltransferase-like protein 4 0.0036 0.0246 0.0364
Mycobacterium leprae PROBABLE THIOESTERASE TESA 0.0099 0.1519 0.4773
Mycobacterium ulcerans polyketide synthase MbtD 0.0037 0.0261 0.0491
Echinococcus granulosus diuretic hormone 44 receptor GPRdih2 0.0048 0.0494 0.0678
Brugia malayi AMP-binding enzyme family protein 0.0111 0.176 0.4427
Loa Loa (eye worm) fatty acid synthase 0.0117 0.1886 0.3137
Onchocerca volvulus 0.0207 0.3688 0.9285
Loa Loa (eye worm) hypothetical protein 0.0048 0.0494 0.0678
Entamoeba histolytica hypothetical protein 0.0036 0.0255 1
Mycobacterium leprae Probable multifunctional mycocerosic acid synthase membrane associated enzyme Mas 0.0115 0.1844 0.6024
Mycobacterium ulcerans polyketide synthase Pks13 0.0167 0.2878 1
Mycobacterium tuberculosis Polyketide synthase Pks12 0.0115 0.1844 0.6264
Toxoplasma gondii type I fatty acid synthase, putative 0.0115 0.1844 1
Toxoplasma gondii type I fatty acid synthase, putative 0.0085 0.1228 0.6447
Mycobacterium tuberculosis Probable multifunctional mycocerosic acid synthase membrane-associated Mas 0.0115 0.1844 0.6264
Echinococcus multilocularis cadherin EGF LAG seven pass G type receptor 0.0048 0.0494 0.0678
Mycobacterium ulcerans fatty acid synthase Fas 0.0037 0.0277 0.0548
Mycobacterium ulcerans thioesterase TesA 0.0099 0.1519 0.506
Onchocerca volvulus Fatty acid synthase homolog 0.0214 0.3837 1
Schistosoma mansoni Guanine nucleotide-binding protein G(s) subunit alpha (Adenylate cyclase-stimulating G alpha protein) 0.0046 0.0454 0.0347
Mycobacterium leprae PHENOLPTHIOCEROL SYNTHESIS TYPE-I POLYKETIDE SYNTHASE PPSB 0.0085 0.1228 0.3657
Mycobacterium tuberculosis Probable polyketide synthase Pks8 0.0086 0.126 0.4153
Toxoplasma gondii beta-ketoacyl synthase, N-terminal domain-containing protein 0.0077 0.1077 0.5576
Loa Loa (eye worm) nucleolar RNA-associated protein alpha 0.031 0.5769 1
Loa Loa (eye worm) hypothetical protein 0.0152 0.2586 0.4375
Brugia malayi Calcitonin receptor-like protein seb-1 0.0152 0.2586 0.6644
Brugia malayi Corticotropin releasing factor receptor 2 precursor, putative 0.0152 0.2586 0.6644
Schistosoma mansoni Guanine nucleotide-binding protein G(s) subunit alpha (Adenylate cyclase-stimulating G alpha protein) 0.0046 0.0454 0.0347
Trypanosoma brucei beta-ketoacyl-ACP synthase 0.003 0.0126 1
Mycobacterium leprae Probable polyketide synthase Pks1 0.0115 0.1844 0.6024
Entamoeba histolytica hypothetical protein 0.0036 0.0255 1
Brugia malayi Beta-ketoacyl synthase, N-terminal domain containing protein 0.0108 0.1695 0.4253
Schistosoma mansoni hypothetical protein 0.0048 0.0494 0.0388
Echinococcus granulosus snurportin 1 0.031 0.5769 1
Mycobacterium leprae Polyketide synthase Pks13 0.0167 0.2878 1
Echinococcus granulosus cadherin EGF LAG seven pass G type receptor 0.0048 0.0494 0.0678
Schistosoma mansoni hypothetical protein 0.0048 0.0494 0.0388
Mycobacterium ulcerans phenolpthiocerol synthesis type-I polyketide synthase PpsE 0.0068 0.0885 0.2759
Mycobacterium ulcerans polyketide synthase 0.0108 0.1695 0.5702
Mycobacterium ulcerans phenolpthiocerol synthesis type-I polyketide synthase PpsA 0.0085 0.1228 0.4004
Brugia malayi AMP-binding enzyme family protein 0.0037 0.0261 0.0404
Mycobacterium tuberculosis Hypothetical protein 0.0036 0.0246 0.0492
Echinococcus multilocularis GPCR, family 2 0.0048 0.0494 0.0678
Echinococcus multilocularis diuretic hormone 44 receptor GPRdih2 0.0048 0.0494 0.0678
Mycobacterium tuberculosis Polyketide synthase Pks2 0.0115 0.1844 0.6264
Mycobacterium leprae PHENOLPTHIOCEROL SYNTHESIS TYPE-I POLYKETIDE SYNTHASE PPSC 0.0115 0.1844 0.6024
Mycobacterium tuberculosis Polyketide synthase Pks13 0.0167 0.2878 1
Mycobacterium tuberculosis Phenolpthiocerol synthesis type-I polyketide synthase PpsA 0.0108 0.1695 0.5727
Wolbachia endosymbiont of Brugia malayi 3-oxoacyl-ACP synthase 0.003 0.0126 0.5
Mycobacterium ulcerans Type I modular polyketide synthase 0.0108 0.1695 0.5702
Brugia malayi oxidoreductase, zinc-binding dehydrogenase family protein 0.0214 0.3837 1
Mycobacterium ulcerans Type I modular polyketide synthase 0.0108 0.1695 0.5702
Mycobacterium ulcerans multifunctional mycocerosic acid synthase membrane-associated Mas 0.0115 0.1844 0.6242
Schistosoma mansoni hypothetical protein 0.0036 0.0255 0.0146
Mycobacterium tuberculosis Probable polyketide synthase Pks7 0.0115 0.1844 0.6264
Schistosoma mansoni 3-oxoacyl-[ACP] synthase 0.003 0.0126 0.0016
Brugia malayi latrophilin 2 splice variant baaae 0.0104 0.1618 0.4045
Brugia malayi Beta-ketoacyl synthase, N-terminal domain containing protein 0.003 0.0126 0.0041
Mycobacterium ulcerans phenolpthiocerol synthesis type-I polyketide synthase PpsB 0.0085 0.1228 0.4004
Mycobacterium tuberculosis Probable polyketide synthase Pks9 0.0068 0.0885 0.2801
Loa Loa (eye worm) GTP-binding regulatory protein Gs alpha-S chain 0.0046 0.0454 0.0606
Echinococcus multilocularis guanine nucleotide binding protein G(s) subunit 0.0046 0.0454 0.0606
Mycobacterium leprae PHENOLPTHIOCEROL SYNTHESIS TYPE-I POLYKETIDE SYNTHASE PPSE 0.0068 0.0885 0.2339

Activities

Activity type Activity value Assay description Source Reference
IC50 (binding) = 74 nM Inhibition of human BACE1 by ECL based assay ChEMBL. 17257835
IC50 (binding) = 74 nM Inhibition of human BACE1 by ECL based assay ChEMBL. 17257835
IC50 (binding) > 20000 nM Inhibition of human BACE1 assessed as sAPPNF accumulation ChEMBL. 17257835
IC50 (binding) > 20000 nM Inhibition of human BACE1 assessed as sAPPNF accumulation ChEMBL. 17257835

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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