Detailed information for compound 155832

Basic information

Technical information
  • TDR Targets ID: 155832
  • Name: (2S)-2-(4,6-dimethylpyrimidin-2-yl)oxy-2-[(5S )-2-oxo-5-(3-phenylphenyl)-1-[(2,4,6-trifluor ophenyl)methyl]-3,4-dihydro-1,4-benzodiazepin -5-yl]acetic acid
  • MW: 638.635 | Formula: C36H29F3N4O4
  • H donors: 2 H acceptors: 5 LogP: 3.82 Rotable bonds: 8
    Rule of 5 violations (Lipinski): 2
  • SMILES: OC(=O)[C@H]([C@]1(NCC(=O)N(c2c1cccc2)Cc1c(F)cc(cc1F)F)c1cccc(c1)c1ccccc1)Oc1nc(C)cc(n1)C
  • InChi: 1S/C36H29F3N4O4/c1-21-15-22(2)42-35(41-21)47-33(34(45)46)36(25-12-8-11-24(16-25)23-9-4-3-5-10-23)28-13-6-7-14-31(28)43(32(44)19-40-36)20-27-29(38)17-26(37)18-30(27)39/h3-18,33,40H,19-20H2,1-2H3,(H,45,46)/t33-,36+/m1/s1
  • InChiKey: VEMZPXZQLOLLKQ-ILFWFZRHSA-N  


Substructure search Similarity search

Network

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Synonyms

  • (2S)-2-[(4,6-dimethyl-2-pyrimidinyl)oxy]-2-[(5S)-2-oxo-5-(3-phenylphenyl)-1-[(2,4,6-trifluorophenyl)methyl]-3,4-dihydro-1,4-benzodiazepin-5-yl]acetic acid
  • (2S)-2-(4,6-dimethylpyrimidin-2-yl)oxy-2-[(5S)-2-oxo-5-(3-phenylphenyl)-1-[(2,4,6-trifluorophenyl)methyl]-3,4-dihydro-1,4-benzodiazepin-5-yl]ethanoic acid
  • (2S)-2-(4,6-dimethylpyrimidin-2-yl)oxy-2-[(5S)-2-keto-5-(3-phenylphenyl)-1-(2,4,6-trifluorobenzyl)-3,4-dihydro-1,4-benzodiazepin-5-yl]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
Homo sapiens cytochrome P450, family 3, subfamily A, polypeptide 4 Starlite/ChEMBL References

Predicted pathogen targets for this compound

By orthology
Species Potential target Known druggable target/s Ortholog Group
Loa Loa (eye worm) hypothetical protein Get druggable targets OG5_126554 All targets in OG5_126554
Leishmania donovani cytochrome p450-like protein Get druggable targets OG5_126554 All targets in OG5_126554
Brugia malayi Cytochrome P450 family protein Get druggable targets OG5_126554 All targets in OG5_126554
Leishmania major cytochrome p450-like protein Get druggable targets OG5_126554 All targets in OG5_126554
Trypanosoma cruzi cytochrome P450, putative Get druggable targets OG5_126554 All targets in OG5_126554
Candida albicans closely related to C.maltosa N-alkane-inducible cytochrome P-450, alkane hydroxylating monooxygenase CYP52A3-b aka P450Alk1A (BA Get druggable targets OG5_126554 All targets in OG5_126554
Leishmania infantum cytochrome p450-like protein Get druggable targets OG5_126554 All targets in OG5_126554
Loa Loa (eye worm) cytochrome P450 family protein Get druggable targets OG5_126554 All targets in OG5_126554
Trypanosoma cruzi cytochrome P450, putative Get druggable targets OG5_126554 All targets in OG5_126554
Trypanosoma congolense cytochrome P450, putative Get druggable targets OG5_126554 All targets in OG5_126554
Mycobacterium ulcerans cytochrome P450 185A4 Cyp185A4 Get druggable targets OG5_126554 All targets in OG5_126554
Trypanosoma brucei gambiense cytochrome P450, putative Get druggable targets OG5_126554 All targets in OG5_126554
Trypanosoma brucei cytochrome P450, putative Get druggable targets OG5_126554 All targets in OG5_126554
Candida albicans cytochrome P450 556 Get druggable targets OG5_126554 All targets in OG5_126554
Candida albicans cytochrome P450 56 Get druggable targets OG5_126554 All targets in OG5_126554
Candida albicans similar to C.maltosa N-alkane inducible cytochrome P-450, ALK8 CYP52A11 Get druggable targets OG5_126554 All targets in OG5_126554
Leishmania braziliensis cytochrome p450-like protein Get druggable targets OG5_126554 All targets in OG5_126554
Brugia malayi Cytochrome P450 family protein Get druggable targets OG5_126554 All targets in OG5_126554
Leishmania mexicana cytochrome p450-like protein Get druggable targets OG5_126554 All targets in OG5_126554
Loa Loa (eye worm) CYP4Cod1 Get druggable targets OG5_126554 All targets in OG5_126554
Loa Loa (eye worm) cytochrome P450 family protein Get druggable targets OG5_126554 All targets in OG5_126554
Candida albicans similar to C.maltosa N-alkane inducible cytochrome P-450, ALK8 CYP52A11 Get druggable targets OG5_126554 All targets in OG5_126554
By sequence similarity to non orthologous known druggable targets
Species Potential target Known druggable target Length Alignment span Identity
Echinococcus multilocularis pyroglutamylated rfamide peptide receptor Endothelin receptor   426 aa 412 aa 21.1 %
Brugia malayi cytochrome P450 cytochrome P450, family 3, subfamily A, polypeptide 4 502 aa 492 aa 24.2 %
Echinococcus granulosus pyroglutamylated rfamide peptide receptor Endothelin receptor   426 aa 412 aa 20.1 %
Obtained from network model

Ranking Plot

Putative Targets List

Species Potential target Raw Global Species
Mycobacterium ulcerans cytochrome P450 185A4 Cyp185A4 0.0015 0.0768 0.5
Brugia malayi RNA recognition motif domain containing protein 0.0066 1 1
Loa Loa (eye worm) RNA recognition domain-containing protein domain-containing protein 0.0066 1 1
Loa Loa (eye worm) cytochrome P450 family protein 0.0015 0.0768 0.0768
Schistosoma mansoni tar DNA-binding protein 0.0066 1 0.5
Echinococcus granulosus tar DNA binding protein 0.0066 1 0.5
Loa Loa (eye worm) cytochrome P450 family protein 0.0015 0.0768 0.0768
Loa Loa (eye worm) TAR-binding protein 0.0066 1 1
Trypanosoma cruzi cytochrome P450, putative 0.0015 0.0768 0.5
Echinococcus multilocularis tar DNA binding protein 0.0066 1 0.5
Schistosoma mansoni tar DNA-binding protein 0.0066 1 0.5
Loa Loa (eye worm) CYP4Cod1 0.0015 0.0768 0.0768
Schistosoma mansoni tar DNA-binding protein 0.0066 1 0.5
Trypanosoma cruzi cytochrome P450, putative 0.0015 0.0768 0.5
Trypanosoma brucei cytochrome P450, putative 0.0015 0.0768 0.5
Brugia malayi TAR-binding protein 0.0066 1 1
Loa Loa (eye worm) RNA binding protein 0.0066 1 1
Schistosoma mansoni tar DNA-binding protein 0.0066 1 0.5
Leishmania major cytochrome p450-like protein 0.0015 0.0768 0.5
Schistosoma mansoni tar DNA-binding protein 0.0066 1 0.5

Activities

Activity type Activity value Assay description Source Reference
ABC (functional) = 250 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=15 ChEMBL. 15139756
Duration of action (functional) = 24 hr Duration of action of compound for reducing the blood pressure of rats was determined ChEMBL. 15139756
IC50 (functional) = 7.9 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) = 7.9 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) = 89.8 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) = 89.8 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 (ADMET) = 7 uM Inhibition of human cytochrome P450 3A4 ChEMBL. 15139756
IC50 (ADMET) = 7 uM Inhibition of human cytochrome P450 3A4 ChEMBL. 15139756
IC50 (ADMET) = 28 uM Inhibition of human cytochrome P450 2C9 ChEMBL. 15139756
IC50 (ADMET) = 28 uM Inhibition of human cytochrome P450 2C9 ChEMBL. 15139756
IC50 (ADMET) > 50 uM Inhibition of human cytochrome P450 2D6 ChEMBL. 15139756
IC50 (ADMET) > 50 uM Inhibition of human cytochrome P450 2D6 ChEMBL. 15139756
Kd (functional) = 7.07 Inhibitory potency at native endothelin A and B receptors by inhibiting sarafotoxin Sf6 contractions of rat tracheal rings ChEMBL. 15139756
Kd (functional) = 9.03 Inhibitory potency of the compound at native endothelin A and endothelin B receptors by inhibiting endothelin-1 contractions of rat aortic rings ChEMBL. 15139756
Log D7.4 = 1.8 Log D value of the compound was evaluated ChEMBL. 15139756
Max effect (functional) = -12 mmHg Maximum effect of the compound on reduciton of mean arterial blood pressure was determined in rats ChEMBL. 15139756
pA2 (functional) = 7.07 Inhibitory potency at native endothelin A and B receptors by inhibiting sarafotoxin Sf6 contractions of rat tracheal rings ChEMBL. 15139756
pA2 (functional) = 9.03 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

Bibliographic References

1 literature reference was collected for this gene.

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