Detailed information for compound 1955531

Basic information

Technical information
  • Name: Unnamed compound
  • MW: 564.039 | Formula: C29H33ClF3N3O3
  • H donors: 4 H acceptors: 3 LogP: 4.83 Rotable bonds: 6
    Rule of 5 violations (Lipinski): 2
  • SMILES: O[C@@H]1CCC(CC1)NC(=O)[C@@H]1N[C@H]([C@]2([C@H]1c1cccc(c1F)Cl)C(=O)Nc1c2cc(F)c(c1)F)CC(C)(C)C
  • InChi: 1S/C29H33ClF3N3O3/c1-28(2,3)13-22-29(17-11-19(31)20(32)12-21(17)35-27(29)39)23(16-5-4-6-18(30)24(16)33)25(36-22)26(38)34-14-7-9-15(37)10-8-14/h4-6,11-12,14-15,22-23,25,36-37H,7-10,13H2,1-3H3,(H,34,38)(H,35,39)/t14?,15-,22-,23-,25+,29+/m0/s1
  • InChiKey: CPVLFAPAIXRGNV-OBLDKQPYSA-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 No 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
No druggable targets predicted by sequence similarity
Obtained from network model

Ranking Plot

Putative Targets List

Species Potential target Raw Global Species
Echinococcus multilocularis SWI:SNF matrix associated 0.0013 0.5 0.5
Plasmodium falciparum SWIB/MDM2 domain-containing protein 0.0013 0.5 0.5
Loa Loa (eye worm) brahma associated protein 0.0013 0.5 0.5
Plasmodium vivax SWIB/MDM2 domain-containing protein, putative 0.0013 0.5 0.5
Toxoplasma gondii DNA topoisomerase domain-containing protein 0.0013 0.5 0.5
Toxoplasma gondii SWIB/MDM2 domain-containing protein 0.0013 0.5 0.5
Echinococcus multilocularis Upstream activation factor subunit UAF30 0.0013 0.5 0.5
Schistosoma mansoni hypothetical protein 0.0013 0.5 0.5
Brugia malayi brahma associated protein 60 kDa 0.0013 0.5 0.5
Chlamydia trachomatis SWIB complex protein 0.0013 0.5 0.5
Echinococcus granulosus Upstream activation factor subunit UAF30 0.0013 0.5 0.5
Plasmodium falciparum SWIB/MDM2 domain-containing protein 0.0013 0.5 0.5
Schistosoma mansoni brg-1 associated factor 0.0013 0.5 0.5
Trichomonas vaginalis conserved hypothetical protein 0.0013 0.5 0.5
Brugia malayi SWIB/MDM2 domain containing protein 0.0013 0.5 0.5
Chlamydia trachomatis DNA topoisomerase I 0.0013 0.5 0.5
Echinococcus granulosus SWI:SNF matrix associated 0.0013 0.5 0.5
Onchocerca volvulus 0.0013 0.5 0.5
Echinococcus multilocularis SWI:SNF matrix associated 0.0013 0.5 0.5
Schistosoma mansoni hypothetical protein 0.0013 0.5 0.5
Loa Loa (eye worm) SWIB/MDM2 domain-containing protein 0.0013 0.5 0.5
Plasmodium vivax hypothetical protein, conserved 0.0013 0.5 0.5
Schistosoma mansoni hypothetical protein 0.0013 0.5 0.5
Echinococcus multilocularis SWI:SNF matrix associated 0.0013 0.5 0.5

Activities

Activity type Activity value Assay description Source Reference
IC50 (binding) = 70.2 nM BindingDB_Patents: Fluorescence-polarization Binding Assay. The binding affinity of the MDM2 inhibitors was determined using an optimized, sensitive and quantitative fluorescence polarization-based (FP-based) binding assay using a recombinant human His-tagged MDM2 protein (residues 1-118) and a fluorescently tagged p53-based peptide. The design of the fluorescence probe was based upon a previously reported high-affinity p53-based peptidomimetic compound (5-FAM-ßAla-ßAla-Phe-Met-Aib-pTyr-(6-Cl-LTrp)-Glu-Ac3c-Leu-Asn-NH2 (SEQ ID NO: 1)) (García-Echeverría et al., J. Med. Chem. 43: 3205-3208 (2000)). This tagged peptide is called PMDM6-F. MDM2 protein was serially double diluted in a Dynex 96-well, black, round-bottom plate, and the PMDM6-F peptide was added at 1 nM concentration. The assay was performed in the buffer: 100 mM potassium phosphate, pH 7.5; 100 µg/mL bovine gamma globulin; 0.02% sodium azide, 0.01% Triton X-100) and the polarization values were measured after 3 h of incubation using an ULTRA READER (Tecan U.S. Inc). ChEMBL. No reference
IC50 (binding) = 137.94 nM BindingDB_Patents: Fluorescence-polarization Binding Assay. The binding affinity of the MDM2 inhibitors was optionally determined using a fluorescence polarization-based (FP-based) binding assay using a recombinant human MDM2 protein (residues 5-109) and PMDM6-F as follows: MDM2 protein was serially diluted with a step of 1.8 in a Costar 96-well, black, non binding surface reference 3686 plate, and the PMDM6-F peptide was added at 5 nM concentration. The assay was performed in the buffer: 100 mM potassium phosphate, pH 7.5; 100 µg/mL bovine gamma globulin, 0.01% Triton X-100) and the anisotropy values were measured at equilibrium using a Fusion reader (Packard). ChEMBL. No reference
IC50 (binding) = 157.86 nM BindingDB_Patents: Fluorescence-polarization Binding Assay. The binding affinity of the MDM2 inhibitors was optionally determined using a fluorescence polarization-based (FP-based) binding assay using a recombinant human MDM2 protein (residues 5-109) and PMDM6-F as follows: MDM2 protein was serially diluted with a step of 1.8 in a Costar 96-well, black, non binding surface reference 3686 plate, and the PMDM6-F peptide was added at 5 nM concentration. The assay was performed in the buffer: 100 mM potassium phosphate, pH 7.5; 100 µg/mL bovine gamma globulin, 0.01% Triton X-100) and the anisotropy values were measured at equilibrium using a Fusion reader (Packard). ChEMBL. No reference
IC50 (binding) < 500 nM BindingDB_Patents: Fluorescence-Polarization Binding Assay. The binding affinity of the MDM2 inhibitors was determined using an optimized, sensitive and quantitative fluorescence polarization-based (FP-based) binding assay using a recombinant human His-tagged MDM2 protein (residues 1-118) and a fluorescently tagged p53-based peptide.The design of the fluorescence probe was based upon a previously reported high-affinity p53-based peptidomimetic compound (5-FAM-beta Ala-beta Ala-Phe-Met-Aib-pTyr-(6-Cl-LTrp)-Glu-Ac3c-Leu-Asn-NH2 (SEQ ID NO: 1)) Garcia-Echeverria et al., J. Med. Chem. 43: 3205-3208 (2000)). This tagged peptide is called PMDM6-F. The Kd value of PMDM6-F with the recombinant MDM2 protein was determined from the saturation curve. MDM2 protein was serially double diluted in a Dynex 96-well, black, round-bottom plate, and the PMDM6-F peptide was added at 1 nM concentration. The assay was performed in the buffer: 100 mM potassium phosphate, pH 7.5; 100 ug/mL bovine gamma globulin; 0.02% sodium azide, 0.01% Triton X-100). 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.
 
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External resources for this compound

No external resources registered for this compound

Bibliographic References

No literature references available for this target.

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