Detailed information for compound 1501626

Basic information

Technical information
  • TDR Targets ID: 1501626
  • Name: 1-[4-[6-amino-5-[(E)-methoxyiminomethyl]pyrim idin-4-yl]oxy-2-chlorophenyl]-3-ethylurea
  • MW: 364.787 | Formula: C15H17ClN6O3
  • H donors: 3 H acceptors: 3 LogP: 1.76 Rotable bonds: 8
    Rule of 5 violations (Lipinski): 1
  • SMILES: CCNC(=O)Nc1ccc(cc1Cl)Oc1ncnc(c1/C=N/OC)N
  • InChi: 1S/C15H17ClN6O3/c1-3-18-15(23)22-12-5-4-9(6-11(12)16)25-14-10(7-21-24-2)13(17)19-8-20-14/h4-8H,3H2,1-2H3,(H2,17,19,20)(H2,18,22,23)/b21-7+
  • InChiKey: BJHCYTJNPVGSBZ-QPSGOUHRSA-N  


Substructure search Similarity search

Network

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Synonyms

  • 1-[4-[6-amino-5-[(E)-methoxyiminomethyl]pyrimidin-4-yl]oxy-2-chloro-phenyl]-3-ethyl-urea
  • 1-[4-[[6-amino-5-[(E)-methoxyiminomethyl]-4-pyrimidinyl]oxy]-2-chlorophenyl]-3-ethylurea

Targets

Known targets for this compound

Species Target name Source Bibliographic reference
Homo sapiens fms-related tyrosine kinase 4 Starlite/ChEMBL References
Homo sapiens fms-related tyrosine kinase 1 Starlite/ChEMBL References
Homo sapiens colony stimulating factor 1 receptor Starlite/ChEMBL References
Homo sapiens platelet-derived growth factor receptor, alpha polypeptide Starlite/ChEMBL References
Homo sapiens v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog Starlite/ChEMBL References
Homo sapiens fms-related tyrosine kinase 3 Starlite/ChEMBL References
Homo sapiens ret proto-oncogene Starlite/ChEMBL References
Homo sapiens kinase insert domain receptor Starlite/ChEMBL References

Predicted pathogen targets for this compound

By orthology
Species Potential target Known druggable target/s Ortholog Group
Loa Loa (eye worm) TK/KIN16 protein kinase Get druggable targets OG5_130320 All targets in OG5_130320
Echinococcus granulosus macrophage colony stimulating factor 1 receptor Get druggable targets OG5_132967 All targets in OG5_132967
Onchocerca volvulus Get druggable targets OG5_130320 All targets in OG5_130320
Onchocerca volvulus Tyrosine kinase homolog Get druggable targets OG5_130320 All targets in OG5_130320
Brugia malayi Immunoglobulin I-set domain containing protein Get druggable targets OG5_130320 All targets in OG5_130320
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
Trichomonas vaginalis 3-oxo-5-alpha-steroid 4-dehydrogenase, putative 0.0365 0.2517 0.5
Loa Loa (eye worm) hypothetical protein 0.0109 0.016 0.025
Plasmodium falciparum cytochrome b 0.0401 0.2851 0.5
Trypanosoma cruzi 3-oxo-5-alpha-steroid 4-dehydrogenase, putative 0.0365 0.2517 0.5
Trypanosoma brucei 3-oxo-5-alpha-steroid 4-dehydrogenase-like, putative 0.0365 0.2517 0.5
Toxoplasma gondii apocytochrome b, putative 0.0401 0.2851 1
Loa Loa (eye worm) hypothetical protein 0.0109 0.016 0.025
Brugia malayi cytochrome b 0.0401 0.2851 0.1122
Trichomonas vaginalis 3-oxo-5-alpha-steroid 4-dehydrogenase, putative 0.0365 0.2517 0.5
Echinococcus granulosus roundabout 2 0.0109 0.016 0.016
Leishmania major 3-oxo-5-alpha-steroid 4-dehydrogenase-like protein 0.0365 0.2517 0.5
Entamoeba histolytica steroid 5-alpha reductase, putative 0.0365 0.2517 0.5
Echinococcus multilocularis roundabout 2 0.0109 0.016 1
Onchocerca volvulus Tyrosine kinase homolog 0.0609 0.4762 1
Wolbachia endosymbiont of Brugia malayi cytochrome b subunit of the bc complex 0.0401 0.2851 0.5
Loa Loa (eye worm) TK/KIN16 protein kinase 0.0688 0.5493 1
Schistosoma mansoni cytochrome b 0.0401 0.2851 1
Loa Loa (eye worm) cytochrome b 0.0401 0.2851 0.5169
Brugia malayi Immunoglobulin I-set domain containing protein 0.0688 0.5493 1
Trypanosoma cruzi 3-oxo-5-alpha-steroid 4-dehydrogenase, putative 0.0365 0.2517 0.5
Toxoplasma gondii cytochrome b 0.0401 0.2851 1
Echinococcus granulosus neurotracting:lsamp:neurotrimin:obcam 0.0094 0.0024 0.0024
Loa Loa (eye worm) hypothetical protein 0.0365 0.2517 0.4559
Trichomonas vaginalis 3-oxo-5-alpha-steroid 4-dehydrogenase, putative 0.0365 0.2517 0.5
Echinococcus granulosus cytochrome B 0.0401 0.2851 0.2851
Mycobacterium ulcerans hypothetical protein 0.0365 0.2517 0.5
Schistosoma mansoni cytochrome b 0.0401 0.2851 1
Plasmodium vivax cytochrome b 0.0401 0.2851 0.5
Schistosoma mansoni cell adhesion molecule 0.0094 0.0024 0.0083

Activities

Activity type Activity value Assay description Source Reference
AUC (ADMET) = 6114 ng.hr/ml AUC in BALB/c mouse at 2 mg/kg, iv ChEMBL. 21316232
AUC (ADMET) = 12305 ng.hr/ml AUC in BALB/c mouse at 10 mg/kg, po ChEMBL. 21316232
CL (ADMET) = 5.6 ml/min.kg Clearance in BALB/c mouse at 2 mg/kg, iv ChEMBL. 21316232
Cmax (ADMET) = 2786 ng/ml Cmax in BALB/c mouse at 10 mg/kg, po ChEMBL. 21316232
Cmax (ADMET) = 2987 ng/ml Cmax in BALB/c mouse at 2 mg/kg, iv ChEMBL. 21316232
F (ADMET) = 16 % Oral bioavailability in BALB/c mouse at 10 mg/kg ChEMBL. 21316232
IC50 (binding) = 11 nM Inhibition of VEGFR2 ChEMBL. 21316232
IC50 (binding) = 183 nM Inhibition of RET ChEMBL. 21316232
IC50 (binding) = 513 nM Inhibition of KIT ChEMBL. 21316232
IC50 (binding) = 622 nM Inhibition of CSF1R ChEMBL. 21316232
IC50 (binding) = 1100 nM Inhibition of FLT4 ChEMBL. 21316232
IC50 (binding) = 1110 nM Inhibition of PDGFRalpha ChEMBL. 21316232
IC50 (binding) = 4420 nM Inhibition of FLT1 ChEMBL. 21316232
IC50 (binding) = 4800 nM Inhibition of FLT3 ChEMBL. 21316232
Inhibition (functional) = 90 % Antitumor activity against human A431 cells xenografted mouse model measured at 100 to 200 mg/kg, po after 10 to 14 days ChEMBL. 21316232
Inhibition (functional) = 90 % Antitumor activity against human HCT116 cells xenografted mouse model measured at 100 to 200 mg/kg, po after 10 to 14 days ChEMBL. 21316232
Inhibition (functional) = 90 % Antitumor activity against human A375 cells xenografted mouse model assessed as growth inhibition at 100 mg/kg, po ChEMBL. 21316232
T1/2 (ADMET) = 2.1 hr Half life in BALB/c mouse at 10 mg/kg, po ChEMBL. 21316232
T1/2 (ADMET) = 2.8 hr Half life in BALB/c mouse at 2 mg/kg, iv ChEMBL. 21316232
Vdss (ADMET) = 0.7 L/Kg Volume of distribution at steady state in BALB/c mouse at 2 mg/kg, iv ChEMBL. 21316232

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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