TDR Targets

Basic information

Technical information

TDR Targets ID: 155275
Name: (2S)-2-[(5S)-1-[(2,6-dichlorophenyl)methyl]-2 -oxo-5-(3-phenylphenyl)-3,4-dihydro-1,4-benzo diazepin-5-yl]-2-(4,6-dimethylpyrimidin-2-yl) oxyacetic acid
MW: 653.554 | Formula: C36H30Cl2N4O4
H donors: 2 H acceptors: 5 LogP: 4.78 Rotable bonds: 8
Rule of 5 violations (Lipinski): 2
SMILES: Cc1nc(nc(c1)C)O[C@@H]([C@]1(NCC(=O)N(c2c1cccc2)Cc1c(Cl)cccc1Cl)c1cccc(c1)c1ccccc1)C(=O)O
InChi: 1S/C36H30Cl2N4O4/c1-22-18-23(2)41-35(40-22)46-33(34(44)45)36(26-13-8-12-25(19-26)24-10-4-3-5-11-24)28-14-6-7-17-31(28)42(32(43)20-39-36)21-27-29(37)15-9-16-30(27)38/h3-19,33,39H,20-21H2,1-2H3,(H,44,45)/t33-,36+/m1/s1
InChiKey: FHRCXZSDINFQMI-ILFWFZRHSA-N

Network

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Target Layer

Model Organisms

Species	Viewmode
Arabidopsis thaliana
Caenorhabditis elegans
Dictyostelium discoideum
Drosophila melanogaster
Escherichia coli
Homo sapiens
Mus musculus
Oryza sativa
Saccharomyces cerevisiae
Schmidtea mediterranea
Other organisms

TDR Pathogens:

Species	Viewmode
Brugia malayi
Chlamydia trachomatis
Echinococcus granulosus
Entamoeba histolytica
Echinococcus multilocularis
Giardia lamblia
Leishmania major
Loa Loa (eye worm)
Mycobacterium leprae
Mycobacterium tuberculosis
Mycobacterium ulcerans
Onchocerca volvulus
Plasmodium falciparum
Plasmodium vivax
Schistosoma mansoni
Trypanosoma brucei
Trypanosoma cruzi
Toxoplasma gondii
Treponema pallidum
Trichomonas vaginalis
Wolbachia endosymbiont of Brugia malayi

Other Pathogens:

Species	Viewmode
Babesia bovis
Candida albicans
Cryptosporidium hominis
Cryptosporidium parvum
Leishmania braziliensis
Leishmania donovani
Leishmania infantum
Leishmania mexicana
Neospora caninum
Plasmodium berghei
Plasmodium knowlesi
Plasmodium yoelii
Schistosoma japonicum
Trypanosoma brucei gambiense
Trypanosoma congolense
Theileria parva

Compound Layer

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Clustering layers

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Synonyms

(2S)-2-[(5S)-1-[(2,6-dichlorophenyl)methyl]-2-oxo-5-(3-phenylphenyl)-3,4-dihydro-1,4-benzodiazepin-5-yl]-2-(4,6-dimethylpyrimidin-2-yl)oxy-acetic acid
(2S)-2-[(5S)-1-[(2,6-dichlorophenyl)methyl]-2-oxo-5-(3-phenylphenyl)-3,4-dihydro-1,4-benzodiazepin-5-yl]-2-[(4,6-dimethyl-2-pyrimidinyl)oxy]acetic acid
(2S)-2-[(5S)-1-[(2,6-dichlorophenyl)methyl]-2-oxo-5-(3-phenylphenyl)-3,4-dihydro-1,4-benzodiazepin-5-yl]-2-(4,6-dimethylpyrimidin-2-yl)oxy-ethanoic acid
(2S)-2-[(5S)-1-(2,6-dichlorobenzyl)-2-keto-5-(3-phenylphenyl)-3,4-dihydro-1,4-benzodiazepin-5-yl]-2-(4,6-dimethylpyrimidin-2-yl)oxy-acetic acid

Targets

Known targets for this compound

Species	Target name	Source	Bibliographic reference
Rattus norvegicus	Endothelin receptor	Starlite/ChEMBL	References
Homo sapiens	endothelin receptor type B	Starlite/ChEMBL	References

Predicted pathogen targets for this compound

By orthology

No druggable targets predicted by orthology data

By sequence similarity to non orthologous known druggable targets

Species	Potential target	Known druggable target	Length	Alignment span	Identity
Echinococcus granulosus	pyroglutamylated rfamide peptide receptor	Endothelin receptor	426 aa	412 aa	20.1 %
Echinococcus multilocularis	pyroglutamylated rfamide peptide receptor	Endothelin receptor	426 aa	412 aa	21.1 %

Ranking Plot

Putative Targets List

Species	Potential target	Raw	Global	Species
Brugia malayi	Smad1	0.0092	0.0199	0.0199
Onchocerca volvulus		0.0604	0.2698	0.5
Leishmania major	isocitrate dehydrogenase [NADP], mitochondrial precursor, putative	0.013	0.0386	1
Echinococcus granulosus	tar DNA binding protein	0.1639	0.7748	1
Schistosoma mansoni	tar DNA-binding protein	0.1639	0.7748	1
Brugia malayi	MH2 domain containing protein	0.1344	0.6308	0.6308
Brugia malayi	hypothetical protein	0.0604	0.2698	0.2698
Trypanosoma brucei	isocitrate dehydrogenase [NADP], mitochondrial precursor, putative	0.013	0.0386	1
Toxoplasma gondii	isocitrate dehydrogenase	0.013	0.0386	1
Brugia malayi	Calcitonin receptor-like protein seb-1	0.2101	1	1
Echinococcus multilocularis	tar DNA binding protein	0.1639	0.7748	1
Loa Loa (eye worm)	pigment dispersing factor receptor c	0.2101	1	1
Toxoplasma gondii	isocitrate dehydrogenase	0.013	0.0386	1
Echinococcus multilocularis	isocitrate dehydrogenase 2 (NADP+)	0.013	0.0386	0.0247
Loa Loa (eye worm)	transcription factor SMAD2	0.1344	0.6308	0.6308
Brugia malayi	TAR-binding protein	0.1639	0.7748	0.7748
Schistosoma mansoni	NADP-specific isocitrate dehydrogenase	0.013	0.0386	0.0247
Loa Loa (eye worm)	MH1 domain-containing protein	0.0092	0.0199	0.0199
Loa Loa (eye worm)	hypothetical protein	0.2101	1	1
Echinococcus granulosus	cadherin EGF LAG seven pass G type receptor	0.0665	0.2995	0.3703
Schistosoma mansoni	hypothetical protein	0.0665	0.2995	0.3703
Loa Loa (eye worm)	Smad1	0.0092	0.0199	0.0199
Loa Loa (eye worm)	MH2 domain-containing protein	0.1344	0.6308	0.6308
Echinococcus multilocularis	GPCR, family 2	0.0665	0.2995	0.3703
Brugia malayi	isocitrate dehydrogenase	0.013	0.0386	0.0386
Schistosoma mansoni	hypothetical protein	0.1436	0.6758	0.8688
Echinococcus granulosus	NADP dependent isocitrate dehydrogenase	0.013	0.0386	0.0247
Loa Loa (eye worm)	latrophilin receptor protein 2	0.0665	0.2995	0.2995
Echinococcus multilocularis	cadherin EGF LAG seven pass G type receptor	0.0665	0.2995	0.3703
Schistosoma mansoni	hypothetical protein	0.0665	0.2995	0.3703
Brugia malayi	RNA binding protein	0.1639	0.7748	0.7748
Trypanosoma cruzi	isocitrate dehydrogenase, putative	0.013	0.0386	1
Schistosoma mansoni	tar DNA-binding protein	0.1639	0.7748	1
Plasmodium vivax	isocitrate dehydrogenase [NADP], mitochondrial, putative	0.013	0.0386	1
Loa Loa (eye worm)	MH2 domain-containing protein	0.0092	0.0199	0.0199
Brugia malayi	MH1 domain containing protein	0.0092	0.0199	0.0199
Mycobacterium tuberculosis	Probable isocitrate dehydrogenase [NADP] Icd1 (oxalosuccinate decarboxylase) (IDH) (NADP+-specific ICDH) (IDP)	0.013	0.0386	0.5
Brugia malayi	Latrophilin receptor protein 2	0.0665	0.2995	0.2995
Schistosoma mansoni	tar DNA-binding protein	0.1639	0.7748	1
Schistosoma mansoni	hypothetical protein	0.0665	0.2995	0.3703
Trypanosoma brucei	isocitrate dehydrogenase, putative	0.013	0.0386	1
Brugia malayi	latrophilin 2 splice variant baaae	0.1436	0.6758	0.6758
Echinococcus multilocularis	NADP dependent isocitrate dehydrogenase	0.013	0.0386	0.0247
Schistosoma mansoni	tar DNA-binding protein	0.1639	0.7748	1
Loa Loa (eye worm)	TAR-binding protein	0.1639	0.7748	0.7748
Brugia malayi	Isocitrate dehydrogenase	0.013	0.0386	0.0386
Loa Loa (eye worm)	hypothetical protein	0.1436	0.6758	0.6758
Schistosoma mansoni	tar DNA-binding protein	0.1639	0.7748	1
Echinococcus multilocularis	diuretic hormone 44 receptor GPRdih2	0.0665	0.2995	0.3703
Echinococcus granulosus	diuretic hormone 44 receptor GPRdih2	0.0665	0.2995	0.3703
Loa Loa (eye worm)	hypothetical protein	0.0604	0.2698	0.2698
Brugia malayi	calcium-independent alpha-latrotoxin receptor 2, putative	0.0665	0.2995	0.2995
Brugia malayi	MH2 domain containing protein	0.0092	0.0199	0.0199
Echinococcus multilocularis	isocitrate dehydrogenase	0.013	0.0386	0.0247
Echinococcus granulosus	GPCR family 2	0.0665	0.2995	0.3703
Loa Loa (eye worm)	RNA binding protein	0.1639	0.7748	0.7748
Loa Loa (eye worm)	hypothetical protein	0.0665	0.2995	0.2995
Brugia malayi	MH2 domain containing protein	0.0092	0.0199	0.0199
Loa Loa (eye worm)	RNA recognition domain-containing protein domain-containing protein	0.1639	0.7748	0.7748
Plasmodium falciparum	isocitrate dehydrogenase [NADP], mitochondrial	0.013	0.0386	1
Loa Loa (eye worm)	isocitrate dehydrogenase	0.013	0.0386	0.0386
Brugia malayi	MH1 domain containing protein	0.0092	0.0199	0.0199
Echinococcus multilocularis	NADP dependent isocitrate dehydrogenase	0.013	0.0386	0.0247
Echinococcus multilocularis	NADP dependent isocitrate dehydrogenase	0.013	0.0386	0.0247
Schistosoma mansoni	hypothetical protein	0.0665	0.2995	0.3703
Brugia malayi	RNA recognition motif domain containing protein	0.1639	0.7748	0.7748
Trypanosoma cruzi	isocitrate dehydrogenase [NADP], mitochondrial precursor, putative	0.013	0.0386	1

Activities

Activity type	Activity value	Assay description	Source	Reference
ABC (functional)	= 200 mmHg hr-1	In vivo area between curve (ABC) as calculated from the blood pressure recordings before and after administration of 30 mg/kg of the compound to hypertensiveDahl salt sensitive rats; number of rats=12	ChEMBL.	15139756
Duration of action (functional)	= 18 hr	Duration of action of compound for reducing the blood pressure of rats was determined	ChEMBL.	15139756
IC50 (functional)	= 16.9 nM	Antagonist activity towards human recombinant Endothelin A receptor expressed in chinese hamster ovary (CHO) cells determined using [125I]-ET-1 as radioligand	ChEMBL.	15139756
IC50 (functional)	= 16.9 nM	Antagonist activity towards human recombinant Endothelin A receptor expressed in chinese hamster ovary (CHO) cells determined using [125I]-ET-1 as radioligand	ChEMBL.	15139756
IC50 (functional)	= 25 nM	Antagonist activity towards human recombinant Endothelin B receptor expressed in chinese hamster ovary (CHO) cells determined using [125I]-ET-1 as radioligand	ChEMBL.	15139756
IC50 (functional)	= 25 nM	Antagonist activity towards human recombinant Endothelin B receptor expressed in chinese hamster ovary (CHO) cells determined using [125I]-ET-1 as radioligand	ChEMBL.	15139756
Kd (functional)	= 7.37	Inhibitory potency at native endothelin A and B receptors by inhibiting sarafotoxin Sf6 contractions of rat tracheal rings	ChEMBL.	15139756
Kd (functional)	= 8.98	Inhibitory potency of the compound at native endothelin A and endothelin B receptors by inhibiting endothelin-1 contractions of rat aortic rings	ChEMBL.	15139756
Max effect (functional)	= -15 mmHg	Maximum effect of the compound on reduciton of mean arterial blood pressure was determined in rats	ChEMBL.	15139756
pA2 (functional)	= 7.37	Inhibitory potency at native endothelin A and B receptors by inhibiting sarafotoxin Sf6 contractions of rat tracheal rings	ChEMBL.	15139756
pA2 (functional)	= 8.98	Inhibitory potency of the compound at native endothelin A and endothelin B receptors by inhibiting endothelin-1 contractions of rat aortic rings	ChEMBL.	15139756

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

ChEMBL: CHEMBL318086
PubChem: 11331242

Bibliographic References

1 literature reference was collected for this gene.

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Detailed information for compound 155275