Detailed information for compound 2008362

Basic information

Technical information
  • Name: Unnamed compound
  • MW: 763.966 | Formula: C39H49N5O7S2
  • H donors: 2 H acceptors: 7 LogP: 4.99 Rotable bonds: 9
    Rule of 5 violations (Lipinski): 2
  • SMILES: COc1ccc2c(c1C)nc(cc2O[C@@H]1C[C@@H]2[C@@H](C1)C(=O)N(C)CCCC/C=C\[C@H]1[C@](NC2=O)(C1)C(=O)NS(=O)(=O)C1(C)CC1)c1scc(n1)C(C)C
  • InChi: 1S/C39H49N5O7S2/c1-22(2)30-21-52-35(41-30)29-19-32(26-12-13-31(50-6)23(3)33(26)40-29)51-25-17-27-28(18-25)36(46)44(5)16-10-8-7-9-11-24-20-39(24,42-34(27)45)37(47)43-53(48,49)38(4)14-15-38/h9,11-13,19,21-22,24-25,27-28H,7-8,10,14-18,20H2,1-6H3,(H,42,45)(H,43,47)/b11-9-/t24-,25-,27-,28-,39-/m1/s1
  • InChiKey: CVFQOKIBZTWREC-UDWBKMJLSA-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
Hepatitis C virus Hepatitis C virus serine protease, NS3/NS4A Starlite/ChEMBL No references
Hepatitis C virus Hepatitis C virus NS3 protease/helicase Starlite/ChEMBL No references

Predicted pathogen targets for this compound

By orthology
Species Potential target Known druggable target/s Ortholog Group
Brugia malayi eukaryotic initiation factor 4A Get druggable targets OG5_126984 All targets in OG5_126984
Cryptosporidium parvum eukaryotic initiation factor 4A (eIF4A) (eIF-4A) Get druggable targets OG5_126984 All targets in OG5_126984
Onchocerca volvulus Eukaryotic initiation factor 4A homolog Get druggable targets OG5_126984 All targets in OG5_126984
Trichomonas vaginalis DEAD box ATP-dependent RNA helicase, putative Get druggable targets OG5_126984 All targets in OG5_126984
Candida albicans similar to S. cerevisiae TIF1 (YKR059W) and TIF2 (YJL138C) translation initiation factor eIF4A subunit Get druggable targets OG5_126984 All targets in OG5_126984
Leishmania infantum eukaryotic initiation factor 4a, putative Get druggable targets OG5_126984 All targets in OG5_126984
Cryptosporidium hominis eukaryotic initiation factor 4A (eIF4A) (eIF-4A) Get druggable targets OG5_126984 All targets in OG5_126984
Schistosoma japonicum Eukaryotic initiation factor 4A-III, putative Get druggable targets OG5_126984 All targets in OG5_126984
Babesia bovis eukaryotic translation initiation factor 4A, putative Get druggable targets OG5_126984 All targets in OG5_126984
Echinococcus multilocularis eukaryotic initiation factor 4A III Get druggable targets OG5_126984 All targets in OG5_126984
Giardia lamblia Translation initiation factor eIF-4A, putative Get druggable targets OG5_126984 All targets in OG5_126984
Toxoplasma gondii eukaryotic initiation factor-4A, putative Get druggable targets OG5_126984 All targets in OG5_126984
Leishmania donovani Eukaryotic initiation factor 4A-1 Get druggable targets OG5_126984 All targets in OG5_126984
Leishmania braziliensis eukaryotic initiation factor 4a, putative Get druggable targets OG5_126984 All targets in OG5_126984
Mycobacterium tuberculosis Probable cold-shock DeaD-box protein A homolog DeaD (ATP-dependent RNA helicase dead homolog) Get druggable targets OG5_126984 All targets in OG5_126984
Schistosoma mansoni DEAD box ATP-dependent RNA helicase Get druggable targets OG5_126984 All targets in OG5_126984
Candida albicans similar to S. cerevisiae TIF1 (YKR059W) and TIF2 (YJL138C) translation initiation factor eIF4A subunit Get druggable targets OG5_126984 All targets in OG5_126984
Theileria parva RNA helicase-1, putative Get druggable targets OG5_126984 All targets in OG5_126984
Trypanosoma brucei gambiense eukaryotic initiation factor 4a, putative Get druggable targets OG5_126984 All targets in OG5_126984
Plasmodium vivax RNA helicase-1, putative Get druggable targets OG5_126984 All targets in OG5_126984
Echinococcus granulosus eukaryotic initiation factor 4A III Get druggable targets OG5_126984 All targets in OG5_126984
Plasmodium knowlesi eukaryotic initiation factor 4a, putative Get druggable targets OG5_126984 All targets in OG5_126984
Trypanosoma cruzi Eukaryotic initiation factor 4A-1 Get druggable targets OG5_126984 All targets in OG5_126984
Plasmodium berghei eukaryotic initiation factor 4a, putative Get druggable targets OG5_126984 All targets in OG5_126984
Treponema pallidum ATP-dependent RNA helicase Get druggable targets OG5_126984 All targets in OG5_126984
Schistosoma mansoni DEAD box ATP-dependent RNA helicase Get druggable targets OG5_126984 All targets in OG5_126984
Entamoeba histolytica DEAD/DEAH box helicase, putative Get druggable targets OG5_126984 All targets in OG5_126984
Neospora caninum DEAD-box ATP-dependent RNA helicase 34 (EC 3.6.1.-), related Get druggable targets OG5_126984 All targets in OG5_126984
Trypanosoma cruzi Eukaryotic initiation factor 4A-1 Get druggable targets OG5_126984 All targets in OG5_126984
Leishmania infantum eukaryotic initiation factor 4a, putative Get druggable targets OG5_126984 All targets in OG5_126984
Plasmodium falciparum eukaryotic initiation factor 4A Get druggable targets OG5_126984 All targets in OG5_126984
Schistosoma japonicum Eukaryotic initiation factor 4A-II, putative Get druggable targets OG5_126984 All targets in OG5_126984
Leishmania mexicana Get druggable targets OG5_126984 All targets in OG5_126984
Leishmania major eukaryotic initiation factor 4a, putative Get druggable targets OG5_126984 All targets in OG5_126984
Echinococcus multilocularis eukaryotic initiation factor 4A Get druggable targets OG5_126984 All targets in OG5_126984
Leishmania major eukaryotic initiation factor 4a, putative Get druggable targets OG5_126984 All targets in OG5_126984
Loa Loa (eye worm) hypothetical protein Get druggable targets OG5_126984 All targets in OG5_126984
Plasmodium yoelii RNA helicase-1 Get druggable targets OG5_126984 All targets in OG5_126984
Trichomonas vaginalis DEAD box ATP-dependent RNA helicase, putative Get druggable targets OG5_126984 All targets in OG5_126984
Trichomonas vaginalis DEAD box ATP-dependent RNA helicase, putative Get druggable targets OG5_126984 All targets in OG5_126984
Schistosoma japonicum ATP-dependent RNA helicase eIF4A, putative Get druggable targets OG5_126984 All targets in OG5_126984
Trypanosoma congolense eukaryotic initiation factor 4a, putative Get druggable targets OG5_126984 All targets in OG5_126984
Echinococcus granulosus eukaryotic initiation factor 4A Get druggable targets OG5_126984 All targets in OG5_126984
Trypanosoma brucei Eukaryotic initiation factor 4A-1 Get druggable targets OG5_126984 All targets in OG5_126984
By sequence similarity to non orthologous known druggable targets
Species Potential target Known druggable target Length Alignment span Identity
Schistosoma japonicum expressed protein Hepatitis C virus serine protease, NS3/NS4A   54 aa 44 aa 29.5 %
Trypanosoma brucei hypothetical protein, conserved Hepatitis C virus serine protease, NS3/NS4A   54 aa 55 aa 30.9 %
Mycobacterium tuberculosis Membrane-associated phospholipase C 2 PlcB Hepatitis C virus serine protease, NS3/NS4A   54 aa 49 aa 32.7 %
Schistosoma mansoni hypothetical protein Hepatitis C virus serine protease, NS3/NS4A   54 aa 44 aa 29.5 %
Trypanosoma brucei expression site-associated gene 3 (ESAG3)-like protein Hepatitis C virus serine protease, NS3/NS4A   54 aa 49 aa 28.6 %
Leishmania braziliensis hypothetical protein, conserved Hepatitis C virus serine protease, NS3/NS4A   54 aa 46 aa 26.1 %
Toxoplasma gondii hypothetical protein Hepatitis C virus serine protease, NS3/NS4A   54 aa 50 aa 28.0 %
Mycobacterium ulcerans Maf-like protein Hepatitis C virus serine protease, NS3/NS4A   54 aa 44 aa 38.6 %
Echinococcus granulosus 60S ribosomal protein L8 Hepatitis C virus serine protease, NS3/NS4A   54 aa 48 aa 33.3 %
Entamoeba histolytica hypothetical protein Hepatitis C virus serine protease, NS3/NS4A   54 aa 52 aa 23.1 %
Trypanosoma congolense WD40 repeats, putative Hepatitis C virus serine protease, NS3/NS4A   54 aa 46 aa 28.3 %
Trypanosoma brucei gambiense expression site-associated gene 3 (ESAG3)-like protein, putative Hepatitis C virus serine protease, NS3/NS4A   54 aa 49 aa 28.6 %
Obtained from network model

Ranking Plot

Putative Targets List

Species Potential target Raw Global Species
Schistosoma mansoni DEAD box ATP-dependent RNA helicase 0.003 1 1
Trypanosoma cruzi Eukaryotic initiation factor 4A-1 0.003 1 1
Trichomonas vaginalis Clan CA, family C1, cathepsin L-like cysteine peptidase 0.0027 0.7759 0.7759
Trichomonas vaginalis Clan CA, family C1, papain-like cysteine peptidase 0.0027 0.7759 0.7759
Trichomonas vaginalis Clan CA, family C1, cathepsin L-like cysteine peptidase 0.0027 0.7759 0.7759
Trypanosoma cruzi cysteine peptidase, putative 0.0027 0.7759 0.7759
Brugia malayi Cathepsin L-like precursor 0.0027 0.7759 0.7759
Onchocerca volvulus Eukaryotic initiation factor 4A homolog 0.003 1 1
Brugia malayi Cathepsin L-like precursor 0.0027 0.7759 0.7759
Plasmodium falciparum eukaryotic initiation factor 4A 0.003 1 1
Schistosoma mansoni DEAD box ATP-dependent RNA helicase 0.003 1 1
Trichomonas vaginalis Clan CA, family C1, cathepsin L-like cysteine peptidase 0.0027 0.7759 0.7759
Trichomonas vaginalis Clan CA, family C1, papain-like cysteine peptidase 0.0027 0.7759 0.7759
Onchocerca volvulus 0.0027 0.7759 0.7759
Trichomonas vaginalis Clan CA, family C1, papain-like cysteine peptidase 0.0027 0.7759 0.7759
Entamoeba histolytica cysteine proteinase, putative 0.0027 0.7759 0.7759
Trichomonas vaginalis Clan CA, family C1, cathepsin L-like cysteine peptidase 0.0027 0.7759 0.7759
Onchocerca volvulus 0.0027 0.7759 0.7759
Trichomonas vaginalis Clan CA, family C1, cathepsin L-like cysteine peptidase 0.0027 0.7759 0.7759
Onchocerca volvulus 0.0027 0.7759 0.7759
Giardia lamblia Translation initiation factor eIF-4A, putative 0.003 1 0.5
Trichomonas vaginalis Clan CA, family C1, papain-like cysteine peptidase 0.0027 0.7759 0.7759
Trichomonas vaginalis Clan CA, family C1, papain-like cysteine peptidase 0.0027 0.7759 0.7759
Onchocerca volvulus 0.0027 0.7759 0.7759
Trypanosoma cruzi cysteine peptidase, putative 0.0027 0.7759 0.7759
Trypanosoma cruzi cruzipain precursor, putative 0.0027 0.7759 0.7759
Brugia malayi Cathepsin L-like precursor 0.0027 0.7759 0.7759
Loa Loa (eye worm) fibroinase 0.0027 0.7759 0.7759
Trichomonas vaginalis Clan CA, family C1, cathepsin L-like cysteine peptidase 0.0027 0.7759 0.7759
Trichomonas vaginalis Clan CA, family C1, cathepsin L-like cysteine peptidase 0.0027 0.7759 0.7759
Schistosoma mansoni cathepsin F (C01 family) 0.0027 0.7759 0.7759
Leishmania major eukaryotic initiation factor 4a, putative 0.003 1 1
Entamoeba histolytica DEAD/DEAH box helicase, putative 0.003 1 1
Trichomonas vaginalis Clan CA, family C1, cathepsin L-like cysteine peptidase 0.0027 0.7759 0.7759
Trypanosoma cruzi cysteine peptidase, putative 0.0027 0.7759 0.7759
Mycobacterium tuberculosis Probable cold-shock DeaD-box protein A homolog DeaD (ATP-dependent RNA helicase dead homolog) 0.003 1 0.5
Trichomonas vaginalis Clan CA, family C1, cathepsin L or K-like cysteine peptidase 0.0027 0.7759 0.7759
Echinococcus granulosus cathepsin L cysteine proteinase 0.0027 0.7759 0.7759
Onchocerca volvulus Cathepsin L homolog 0.0027 0.7759 0.7759
Loa Loa (eye worm) cysteine protease 0.0027 0.7759 0.7759
Loa Loa (eye worm) hypothetical protein 0.0027 0.7759 0.7759
Plasmodium vivax RNA helicase-1, putative 0.003 1 1
Echinococcus multilocularis eukaryotic initiation factor 4A 0.003 1 1
Entamoeba histolytica cysteine proteinase, putative 0.0027 0.7759 0.7759
Echinococcus granulosus eukaryotic initiation factor 4A 0.003 1 1
Trichomonas vaginalis Clan CA, family C1, cathepsin L-like cysteine peptidase 0.0027 0.7759 0.7759
Trichomonas vaginalis Clan CA, family C1, cathepsin L-like cysteine peptidase 0.0027 0.7759 0.7759
Onchocerca volvulus 0.0027 0.7759 0.7759
Echinococcus multilocularis eukaryotic initiation factor 4A III 0.003 1 1
Loa Loa (eye worm) Papain cysteine protease/cathepsin propeptide inhibitor-containing protein 0.0027 0.7759 0.7759
Trichomonas vaginalis Clan CA, family C1, papain-like cysteine peptidase 0.0027 0.7759 0.7759
Trichomonas vaginalis Clan CA, family C1, cathepsin L or K-like cysteine peptidase 0.0027 0.7759 0.7759
Trichomonas vaginalis DEAD box ATP-dependent RNA helicase, putative 0.003 1 1
Trichomonas vaginalis Clan CA, family C1, papain-like cysteine peptidase 0.0027 0.7759 0.7759
Trichomonas vaginalis Clan CA, family C1, cathepsin L-like cysteine peptidase 0.0027 0.7759 0.7759
Echinococcus granulosus cathepsin l1 0.0027 0.7759 0.7759
Trichomonas vaginalis DEAD box ATP-dependent RNA helicase, putative 0.003 1 1
Loa Loa (eye worm) hypothetical protein 0.003 1 1
Loa Loa (eye worm) papain family cysteine protease containing protein 0.0027 0.7759 0.7759
Brugia malayi Papain family cysteine protease containing protein 0.0027 0.7759 0.7759
Trichomonas vaginalis DEAD box ATP-dependent RNA helicase, putative 0.003 1 1
Trichomonas vaginalis Clan CA, family C1, cathepsin L-like cysteine peptidase 0.0027 0.7759 0.7759
Onchocerca volvulus 0.0027 0.7759 0.7759
Loa Loa (eye worm) ctsf protein 0.0027 0.7759 0.7759
Entamoeba histolytica cysteine protease, putative 0.0027 0.7759 0.7759
Echinococcus granulosus eukaryotic initiation factor 4A III 0.003 1 1
Trypanosoma cruzi cysteine peptidase, putative 0.0027 0.7759 0.7759
Trichomonas vaginalis Clan CA, family C1, papain-like cysteine peptidase 0.0027 0.7759 0.7759
Echinococcus granulosus cathepsin l cysteine peptidase 0.0027 0.7759 0.7759
Onchocerca volvulus Cathepsin F homolog 0.0027 0.7759 0.7759
Trypanosoma cruzi Eukaryotic initiation factor 4A-1 0.003 1 1
Toxoplasma gondii eukaryotic initiation factor-4A, putative 0.003 1 1
Trichomonas vaginalis Clan CA, family C1, papain-like cysteine peptidase 0.0027 0.7759 0.7759
Schistosoma mansoni cathepsin F (C01 family) 0.0027 0.7759 0.7759
Brugia malayi Cathepsin L-like precursor 0.0027 0.7759 0.7759
Brugia malayi Cathepsin L-like precursor 0.0027 0.7759 0.7759
Trypanosoma brucei Eukaryotic initiation factor 4A-1 0.003 1 1
Leishmania major eukaryotic initiation factor 4a, putative 0.003 1 1
Trichomonas vaginalis Clan CA, family C1, cathepsin L-like cysteine peptidase 0.0027 0.7759 0.7759
Onchocerca volvulus 0.0027 0.7759 0.7759
Trichomonas vaginalis Clan CA, family C1, cathepsin L-like cysteine peptidase 0.0027 0.7759 0.7759
Brugia malayi Cathepsin L-like precursor 0.0027 0.7759 0.7759
Onchocerca volvulus Cathepsin L homolog 0.0027 0.7759 0.7759
Treponema pallidum ATP-dependent RNA helicase 0.003 1 0.5

Activities

Activity type Activity value Assay description Source Reference
Ki (binding) = 0.25 nM BindingDB_Patents: Inhibition Assay. The inhibition of full-length hepatitis C NS3 protease enzyme was measured essentially as described in Poliakov, 2002 Prot Expression & Purification 25 363 371. Briefly, the hydrolysis of a depsipeptide substrate, Ac-DED(Edans)EEAbu[COO]ASK(Dabcyl)-NH2 (AnaSpec, San Jose, USA), was measured spectrofluorometrically in the presence of a peptide cofactor, KKGSVVIVGRIVLSGK (Ake Engstrom, Department of Medical Biochemistry and Microbiology, Uppsala University, Sweden). [Landro, 1997 #Biochem 36 9340-9348]. The enzyme (1 nM) was incubated in 50 mM HEPES, pH 7.5, 10 mM DTT, 40% glycerol, 0.1% n-octyl-D-glucoside, with 25 µM NS4A cofactor and inhibitor at 30 C. for 10 min, whereupon the reaction was initiated by addition of 0.5 µM substrate. Inhibitors were dissolved in DMSO, sonicated for 30 sec. and vortexed. ChEMBL. No reference
Ki (binding) = 0.25 nM BindingDB_Patents: Enzymatic Assay. The aim of this in vitro assay was to measure the inhibition of HCV NS3/4A protease complexes by the compounds of the present invention. This assay provides an indication of how effective compounds of the present invention would be in inhibiting HCV NS3/4A proteolytic activity. The inhibition of full-length hepatitis C NS3 protease enzyme was measured essentially as described in Poliakov, 2002 Prot Expression & Purification 25 363 371. Briefly, the hydrolysis of a depsipeptide substrate,  Ac-DED(Edans)EEAbuÏ[COO]ASK(Dabcyl)-NH2 (AnaSpec, San Jose, USA), was measured spectrofluorometrically in the presence of a peptide cofactor, KKGSVVIVGRIVLSGK (â «ke Engstrom, Department of Medical Biochemistry and Microbiology, Uppsala University, Sweden). [Landro, 1997 #Biochem 36 9340-9348]. ChEMBL. No reference
Ki (binding) = 0.25 nM BindingDB_Patents: Enzymatic Assay. The aim of this in vitro assay was to measure the inhibition of HCV NS3/4A protease complexes by the compounds of the present invention. This assay provides an indication of how effective compounds of the present invention would be in inhibiting HCV NS3/4A proteolytic activity. The inhibition of full-length hepatitis C NS3 protease enzyme was measured essentially as described in Poliakov, 2002 Prot Expression & Purification 25 363 371. Briefly, the hydrolysis of a depsipeptide substrate,  Ac-DED(Edans)EEAbuÏ[COO]ASK(Dabcyl)-NH2 (AnaSpec, San Jose, USA), was measured spectrofluorometrically in the presence of a peptide cofactor, KKGSVVIVGRIVLSGK (â «ke Engstrom, Department of Medical Biochemistry and Microbiology, Uppsala University, Sweden). [Landro, 1997 #Biochem 36 9340-9348]. ChEMBL. No reference
Ki (binding) = 0.25 nM BindingDB_Patents: Inhibition Assay. The inhibition of full-length hepatitis C NS3 protease enzyme was measured essentially as described in Poliakov, 2002 Prot Expression & Purification 25 363 371. Briefly, the hydrolysis of a depsipeptide substrate, Ac-DED(Edans)EEAbu[COO]ASK(Dabcyl)-NH2 (AnaSpec, San Jose, USA), was measured spectrofluorometrically in the presence of a peptide cofactor, KKGSVVIVGRIVLSGK (Ake Engstrom, Department of Medical Biochemistry and Microbiology, Uppsala University, Sweden). [Landro, 1997 #Biochem 36 9340-9348]. The enzyme (1 nM) was incubated in 50 mM HEPES, pH 7.5, 10 mM DTT, 40% glycerol, 0.1% n-octyl-D-glucoside, with 25 µM NS4A cofactor and inhibitor at 30 C. for 10 min, whereupon the reaction was initiated by addition of 0.5 µM substrate. Inhibitors were dissolved in DMSO, sonicated for 30 sec. and vortexed. 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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