Detailed information for compound 1958588

Basic information

Technical information
  • Name: Unnamed compound
  • MW: 523.026 | Formula: C27H31ClN6O3
  • H donors: 1 H acceptors: 4 LogP: 4.82 Rotable bonds: 8
    Rule of 5 violations (Lipinski): 2
  • SMILES: CCOC(c1nc2c(n1C[C@@H]1CC[C@H](CC1)C)c(nc(c2)c1noc(=O)[nH]1)c1cncc(c1)Cl)C1CC1
  • InChi: 1S/C27H31ClN6O3/c1-3-36-24(17-8-9-17)26-31-20-11-21(25-32-27(35)37-33-25)30-22(18-10-19(28)13-29-12-18)23(20)34(26)14-16-6-4-15(2)5-7-16/h10-13,15-17,24H,3-9,14H2,1-2H3,(H,32,33,35)/t15-,16-,24?
  • InChiKey: QYQGHXHJFCZPRE-PGUYCLEYSA-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
Toxoplasma gondii DNA topoisomerase domain-containing protein 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 SWIB/MDM2 domain-containing protein 0.0013 0.5 0.5
Chlamydia trachomatis SWIB complex protein 0.0013 0.5 0.5
Plasmodium falciparum SWIB/MDM2 domain-containing protein 0.0013 0.5 0.5
Brugia malayi brahma associated protein 60 kDa 0.0013 0.5 0.5
Schistosoma mansoni hypothetical protein 0.0013 0.5 0.5
Echinococcus granulosus Upstream activation factor subunit UAF30 0.0013 0.5 0.5
Echinococcus multilocularis Upstream activation factor subunit UAF30 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
Chlamydia trachomatis DNA topoisomerase I 0.0013 0.5 0.5
Brugia malayi SWIB/MDM2 domain containing protein 0.0013 0.5 0.5
Echinococcus granulosus SWI:SNF matrix associated 0.0013 0.5 0.5
Echinococcus multilocularis SWI:SNF matrix associated 0.0013 0.5 0.5
Onchocerca volvulus 0.0013 0.5 0.5
Loa Loa (eye worm) SWIB/MDM2 domain-containing protein 0.0013 0.5 0.5
Schistosoma mansoni hypothetical 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) = 1 nM BindingDB_Patents: FRET Assay. Methods: An HDM2 FRET assay was developed to assess the compounds' inhibitory activity towards binding of p53 protein. A truncated version of HDM2 with residues 17 to 125 (containing p53 binding surface, Science (1994) 265, 346-355), with N-terminal His and Thioredoxin tag was generated in pET32a expression vector and expressed in E. coli strain BL21(DE3)Rosetta. Protein was purified using Ni-affinity chromatography, followed by size exclusion chromatography using Superdex 75 26/60 column. To assess inhibition of p53 binding to HDM2, a FITC labeled 8-mer peptide (SEQ ID NO:1: Ac-Phe-Arg-Dpr-Ac6c-(6-Br)Trp-Glu-Glu-Leu-NH2; Anal Biochem. 2004 Aug. 1; 331(1):138-46) with strong affinity towards the p53 binding pocket of HDM2 was used. The HDM2 assay buffer contained 1x Phosphate Buffered Saline (Invitrogen, Cat#14190), 0.01% BSA (Jackson ImmunoResearch, Cat#001-000-162), 0.01% Tween-20. In the 1x assay buffer recombinant HDM2 protein, peptide and Lumi-4-Tb Cryptate-conjugate mouse. ChEMBL. No reference
IC50 (binding) = 1 nM BindingDB_Patents: FRET Assay. Methods: An HDM2 FRET assay was developed to assess the compounds' inhibitory activity towards binding of p53 protein. A truncated version of HDM2 with residues 17 to 125 (containing p53 binding surface, Science (1994) 265, 346-355), with N-terminal His and Thioredoxin tag was generated in pET32a expression vector and expressed in E. coli strain BL21(DE3)Rosetta. Protein was purified using Ni-affinity chromatography, followed by size exclusion chromatography using Superdex 75 26/60 column. To assess inhibition of p53 binding to HDM2, a FITC labeled 8-mer peptide (SEQ ID NO:1: Ac-Phe-Arg-Dpr-Ac6c-(6-Br)Trp-Glu-Glu-Leu-NH2; Anal Biochem. 2004 Aug. 1; 331(1):138-46) with strong affinity towards the p53 binding pocket of HDM2 was used. The HDM2 assay buffer contained 1x Phosphate Buffered Saline (Invitrogen, Cat#14190), 0.01% BSA (Jackson ImmunoResearch, Cat#001-000-162), 0.01% Tween-20. ChEMBL. No reference
IC50 (binding) = 2 nM BindingDB_Patents: FRET Assay. Methods: An HDM2 FRET assay was developed to assess the compounds' inhibitory activity towards binding of p53 protein. A truncated version of HDM2 with residues 17 to 125 (containing p53 binding surface, Science (1994) 265, 346-355), with N-terminal His and Thioredoxin tag was generated in pET32a expression vector and expressed in E. coli strain BL21(DE3)Rosetta. Protein was purified using Ni-affinity chromatography, followed by size exclusion chromatography using Superdex 75 26/60 column. To assess inhibition of p53 binding to HDM2, a FITC labeled 8-mer peptide (SEQ ID NO:1: Ac-Phe-Arg-Dpr-Ac6c-(6-Br)Trp-Glu-Glu-Leu-NH2; Anal Biochem. 2004 Aug. 1; 331(1):138-46) with strong affinity towards the p53 binding pocket of HDM2 was used. The HDM2 assay buffer contained 1x Phosphate Buffered Saline (Invitrogen, Cat#14190), 0.01% BSA (Jackson ImmunoResearch, Cat#001-000-162), 0.01% Tween-20. In the 1x assay buffer recombinant HDM2 protein, peptide and Lumi-4-Tb Cryptate-conjugate mouse. ChEMBL. No reference
IC50 (binding) = 2 nM BindingDB_Patents: FRET Assay. Methods: An HDM2 FRET assay was developed to assess the compounds' inhibitory activity towards binding of p53 protein. A truncated version of HDM2 with residues 17 to 125 (containing p53 binding surface, Science (1994) 265, 346-355), with N-terminal His and Thioredoxin tag was generated in pET32a expression vector and expressed in E. coli strain BL21(DE3)Rosetta. Protein was purified using Ni-affinity chromatography, followed by size exclusion chromatography using Superdex 75 26/60 column. To assess inhibition of p53 binding to HDM2, a FITC labeled 8-mer peptide (SEQ ID NO:1: Ac-Phe-Arg-Dpr-Ac6c-(6-Br)Trp-Glu-Glu-Leu-NH2; Anal Biochem. 2004 Aug. 1; 331(1):138-46) with strong affinity towards the p53 binding pocket of HDM2 was used. The HDM2 assay buffer contained 1x Phosphate Buffered Saline (Invitrogen, Cat#14190), 0.01% BSA (Jackson ImmunoResearch, Cat#001-000-162), 0.01% Tween-20. ChEMBL. No reference
IC50 (binding) = 4 nM BindingDB_Patents: FRET Assay. Methods: An HDM2 FRET assay was developed to assess the compounds' inhibitory activity towards binding of p53 protein. A truncated version of HDM2 with residues 17 to 125 (containing p53 binding surface, Science (1994) 265, 346-355), with N-terminal His and Thioredoxin tag was generated in pET32a expression vector and expressed in E. coli strain BL21(DE3)Rosetta. Protein was purified using Ni-affinity chromatography, followed by size exclusion chromatography using Superdex 75 26/60 column. To assess inhibition of p53 binding to HDM2, a FITC labeled 8-mer peptide (SEQ ID NO:1: Ac-Phe-Arg-Dpr-Ac6c-(6-Br)Trp-Glu-Glu-Leu-NH2; Anal Biochem. 2004 Aug. 1; 331(1):138-46) with strong affinity towards the p53 binding pocket of HDM2 was used. The HDM2 assay buffer contained 1x Phosphate Buffered Saline (Invitrogen, Cat#14190), 0.01% BSA (Jackson ImmunoResearch, Cat#001-000-162), 0.01% Tween-20. In the 1x assay buffer recombinant HDM2 protein, peptide and Lumi-4-Tb Cryptate-conjugate mouse. ChEMBL. No reference
IC50 (binding) = 4 nM BindingDB_Patents: FRET Assay. Methods: An HDM2 FRET assay was developed to assess the compounds' inhibitory activity towards binding of p53 protein. A truncated version of HDM2 with residues 17 to 125 (containing p53 binding surface, Science (1994) 265, 346-355), with N-terminal His and Thioredoxin tag was generated in pET32a expression vector and expressed in E. coli strain BL21(DE3)Rosetta. Protein was purified using Ni-affinity chromatography, followed by size exclusion chromatography using Superdex 75 26/60 column. To assess inhibition of p53 binding to HDM2, a FITC labeled 8-mer peptide (SEQ ID NO:1: Ac-Phe-Arg-Dpr-Ac6c-(6-Br)Trp-Glu-Glu-Leu-NH2; Anal Biochem. 2004 Aug. 1; 331(1):138-46) with strong affinity towards the p53 binding pocket of HDM2 was used. The HDM2 assay buffer contained 1x Phosphate Buffered Saline (Invitrogen, Cat#14190), 0.01% BSA (Jackson ImmunoResearch, Cat#001-000-162), 0.01% Tween-20. 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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