Detailed information for compound 2017975

Basic information

Technical information
  • Name: Unnamed compound
  • MW: 747.7 | Formula: C37H41Cl2FN2O7S
  • H donors: 2 H acceptors: 6 LogP: 6.29 Rotable bonds: 13
    Rule of 5 violations (Lipinski): 2
  • SMILES: COc1cc(ccc1C(=O)O)NC(=O)C[C@@]1(C)C[C@H](c2cccc(c2)Cl)[C@H](N(C1=O)[C@@H](C1CC1)CS(=O)(=O)C(C)(C)C)c1ccc(c(c1)F)Cl
  • InChi: 1S/C37H41Cl2FN2O7S/c1-36(2,3)50(47,48)20-30(21-9-10-21)42-33(23-11-14-28(39)29(40)16-23)27(22-7-6-8-24(38)15-22)18-37(4,35(42)46)19-32(43)41-25-12-13-26(34(44)45)31(17-25)49-5/h6-8,11-17,21,27,30,33H,9-10,18-20H2,1-5H3,(H,41,43)(H,44,45)/t27-,30-,33-,37-/m1/s1
  • InChiKey: QGOICCMBEDDFCI-NXQGQTBASA-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
Homo sapiens MDM2 proto-oncogene, E3 ubiquitin protein ligase Starlite/ChEMBL References
Homo sapiens cytochrome P450, family 3, subfamily A, polypeptide 4 Starlite/ChEMBL No references

Predicted pathogen targets for this compound

By orthology
Species Potential target Known druggable target/s Ortholog Group
Candida albicans similar to C.maltosa N-alkane inducible cytochrome P-450, ALK8 CYP52A11 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
Loa Loa (eye worm) 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
Leishmania major cytochrome p450-like protein 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
Loa Loa (eye worm) cytochrome P450 family protein 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
Leishmania infantum cytochrome p450-like protein 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
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
Brugia malayi Cytochrome P450 family protein 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
Trypanosoma brucei cytochrome P450, putative 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
Trypanosoma cruzi cytochrome P450, putative 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) hypothetical protein 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 donovani 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
By sequence similarity to non orthologous known druggable targets
Species Potential target Known druggable target Length Alignment span Identity
Brugia malayi cytochrome P450 cytochrome P450, family 3, subfamily A, polypeptide 4 502 aa 492 aa 24.2 %
Obtained from network model

Ranking Plot

Putative Targets List

Species Potential target Raw Global Species
Chlamydia trachomatis DNA topoisomerase I 0.0013 0.8119 0.5
Brugia malayi SWIB/MDM2 domain containing protein 0.0013 0.8119 0.8119
Trypanosoma brucei cytochrome P450, putative 0.0015 1 1
Echinococcus multilocularis SWI:SNF matrix associated 0.0013 0.8119 1
Trypanosoma cruzi cytochrome P450, putative 0.0015 1 1
Echinococcus granulosus Upstream activation factor subunit UAF30 0.0013 0.8119 1
Toxoplasma gondii DNA topoisomerase domain-containing protein 0.0013 0.8119 1
Brugia malayi brahma associated protein 60 kDa 0.0013 0.8119 0.8119
Plasmodium falciparum SWIB/MDM2 domain-containing protein 0.0013 0.8119 1
Plasmodium vivax hypothetical protein, conserved 0.0013 0.8119 0.5
Loa Loa (eye worm) cytochrome P450 family protein 0.0015 1 1
Trypanosoma cruzi cytochrome P450, putative 0.0015 1 1
Echinococcus multilocularis SWI:SNF matrix associated 0.0013 0.8119 1
Trichomonas vaginalis conserved hypothetical protein 0.0013 0.8119 0.5
Plasmodium falciparum SWIB/MDM2 domain-containing protein 0.0013 0.8119 1
Schistosoma mansoni hypothetical protein 0.0013 0.8119 1
Brugia malayi Cytochrome P450 family protein 0.0015 1 1
Loa Loa (eye worm) CYP4Cod1 0.0015 1 1
Echinococcus granulosus SWI:SNF matrix associated 0.0013 0.8119 1
Echinococcus multilocularis SWI:SNF matrix associated 0.0013 0.8119 1
Brugia malayi brahma associated protein 60 kDa 0.0013 0.8119 0.8119
Chlamydia trachomatis SWIB complex protein 0.0013 0.8119 0.5
Schistosoma mansoni hypothetical protein 0.0013 0.8119 1
Loa Loa (eye worm) brahma associated protein 0.0013 0.8119 0.8119
Toxoplasma gondii SWIB/MDM2 domain-containing protein 0.0013 0.8119 1
Schistosoma mansoni hypothetical protein 0.0013 0.8119 1
Mycobacterium ulcerans cytochrome P450 185A4 Cyp185A4 0.0015 1 0.5
Onchocerca volvulus 0.0013 0.8119 1
Schistosoma mansoni brg-1 associated factor 0.0013 0.8119 1
Loa Loa (eye worm) cytochrome P450 family protein 0.0015 1 1
Loa Loa (eye worm) hypothetical protein 0.0011 0.5833 0.5833
Loa Loa (eye worm) SWIB/MDM2 domain-containing protein 0.0013 0.8119 0.8119
Leishmania major cytochrome p450-like protein 0.0015 1 1
Echinococcus multilocularis Upstream activation factor subunit UAF30 0.0013 0.8119 1
Plasmodium vivax SWIB/MDM2 domain-containing protein, putative 0.0013 0.8119 0.5

Activities

Activity type Activity value Assay description Source Reference
Activity (ADMET) = 0 % Activation of human PXR at 2 uM relative to control ChEMBL. 25384157
Activity (ADMET) <= 5 % Toxicity in human SJSA1 cells xenografted athymic nude mouse assessed as body weight loss at 10 to 50 mg/kg, po qd for 4 days ChEMBL. 25384157
Activity (ADMET) = 63 % Time-dependent inhibition of CYP3A4 (unknown origin) assessed as remaining activity at 10 uM after 30 mins ChEMBL. 25384157
ED50 (functional) = 2.6 mg kg-1 Antitumor activity against human SJSA1 cells xenografted in athymic nude mouse assessed as tumor growth inhibition administered orally qd for 4 days ChEMBL. 25384157
IC50 (binding) = 0.33 nM BindingDB_Patents: Homogenous Time-Resolved Fluorescence Assay (HTRF). The standard assay conditions for the in vitro HTRF assay consisted of a 50 ul total reaction volume in black 384-well Costar polypropylene plates in 1PBS buffer pH 7.4, 1 mM DTT, 0.1% BSA, 2.5 nM GST-hMDM2 (aa 1-188), 5 nM biotinylated-p53 (aa 1-83), 1.8 nM SA-XLent (Cisbio; Bedford, Mass.), 0.6 nM anti-GST cryptate monoclonal antibody (Cisbio; Bedford, Mass.) and 200 mM KF. Amino acid residues 1-188 of human MDM2 were expressed as an amino-terminal glutathione S-transferase (GST) fusion protein (GST-hMDM2) in Escherichia coli. Residues 1-83 of human p53 were expressed as an amino-terminal AviTag-TrxA-6His fusion protein (biotinylated p53) in E. coli. Each protein was purified from cell paste by affinity chromatography.Specifically, 10 uL of GST-hMDM2 was incubated with 10 ul of diluted compound (various concentrations, serially diluted) in 10% DMSO for 20 minutes at room temperature. 20 uL of biotinylated-p53 was added to the GST-hMDM2+compound mixture. ChEMBL. No reference
IC50 (binding) = 0.6 nM Binding affinity to human GST-thrombin-tagged MDM2 ( 1 to 188 aa) assessed as inhibition of interaction with human p53 preincubated with compound for 20 mins by HTRF assay in presence of 15% human serum ChEMBL. 25384157
Inhibition (ADMET) < 10 % Inhibition of CYP3A4 (unknown origin) at 3 uM ChEMBL. 25384157
Kd (binding) = 257 pM Binding affinity to human MDM2 by by isothermal titration calorimetry ChEMBL. 25384157

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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