Detailed information for compound 1684187

Basic information

Technical information
  • Name: Unnamed compound
  • MW: 540.658 | Formula: C27H40N8O4
  • H donors: 5 H acceptors: 6 LogP: 1.79 Rotable bonds: 12
    Rule of 5 violations (Lipinski): 2
  • SMILES: O=C(Nc1ccc(cc1)C(C)(C)C)NCCCN(C(C)C)C[C@H]1O[C@H]([C@@H]([C@@H]1O)O)n1cnc2c1ncnc2N
  • InChi: 1S/C27H40N8O4/c1-16(2)34(12-6-11-29-26(38)33-18-9-7-17(8-10-18)27(3,4)5)13-19-21(36)22(37)25(39-19)35-15-32-20-23(28)30-14-31-24(20)35/h7-10,14-16,19,21-22,25,36-37H,6,11-13H2,1-5H3,(H2,28,30,31)(H2,29,33,38)/t19-,21-,22-,25-/m1/s1
  • InChiKey: MTLMDZJUGDUTCP-PTGPVQHPSA-N  


Substructure search Similarity search

Network

Hover on a compound node to display the structore

Synonyms

No synonyms found for this compound

Targets

Known targets for this compound

Species Target name Source Bibliographic reference
Homo sapiens DOT1-like histone H3K79 methyltransferase Starlite/ChEMBL References

Predicted pathogen targets for this compound

By orthology
Species Potential target Known druggable target/s Ortholog Group
Echinococcus granulosus histone h3 methyltransferase Get druggable targets OG5_130680 All targets in OG5_130680
Schistosoma japonicum ko:K05302 histone-lysine N-methyltransferase [EC2.1.1.43], putative Get druggable targets OG5_130680 All targets in OG5_130680
Schistosoma mansoni histone J3 methyltransferase Get druggable targets OG5_130680 All targets in OG5_130680
Brugia malayi Histone-lysine N-methyltransferase, H3 lysine-79 specific Get druggable targets OG5_130680 All targets in OG5_130680
Loa Loa (eye worm) hypothetical protein Get druggable targets OG5_130680 All targets in OG5_130680
Echinococcus multilocularis histone h3 methyltransferase Get druggable targets OG5_130680 All targets in OG5_130680
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
Wolbachia endosymbiont of Brugia malayi IMP dehydrogenase 0.0505 1 0.5
Trypanosoma cruzi inosine-5'-monophosphate dehydrogenase, putative 0.0505 1 0.5
Mycobacterium leprae Probable inosine-5'-monophosphate dehydrogenase GuaB2 (IMP dehydrogenase) (IMPDH) (IMPD) 0.0505 1 1
Brugia malayi inosine-5'-monophosphate dehydrogenase 0.021 0.1572 0.1572
Mycobacterium ulcerans inosine 5-monophosphate dehydrogenase 0.0475 0.9144 0.8869
Onchocerca volvulus Putative GMP reductase 0.021 0.1572 0.5
Mycobacterium leprae Probable inosine-5'-monophosphate dehydrogenase GuaB3 (IMP dehydrogenase 2) (inosinic acid dehydrogenase) (inosinate dehydrogena 0.0265 0.315 0.0954
Mycobacterium tuberculosis Probable inosine-5'-monophosphate dehydrogenase GuaB2 (imp dehydrogenase) (inosinic acid dehydrogenase) (inosinate dehydrogenase 0.0505 1 1
Echinococcus multilocularis inosine 5' monophosphate dehydrogenase 2 0.0505 1 1
Brugia malayi GMP reductase 0.021 0.1572 0.1572
Loa Loa (eye worm) IMP dehydrogenase 1 0.0505 1 1
Leishmania major inosine-5-monophosphate dehydrogenase 0.0505 1 0.5
Trypanosoma cruzi inosine-5'-monophosphate dehydrogenase, putative 0.0505 1 0.5
Loa Loa (eye worm) GMP reductase 0.021 0.1572 0.1572
Brugia malayi inosine-5'-monophosphate dehydrogenase 0.021 0.1572 0.1572
Plasmodium vivax inosine-5'-monophosphate dehydrogenase, putative 0.0475 0.9144 0.5
Leishmania major guanosine monophosphate reductase 0.0505 1 0.5
Trypanosoma cruzi GMP reductase 0.0505 1 0.5
Trypanosoma brucei GMP reductase 0.0505 1 0.5
Trypanosoma cruzi GMP reductase 0.0505 1 0.5
Schistosoma mansoni inosine-5-monophosphate dehydrogenase 0.0505 1 1
Trypanosoma brucei inosine-5'-monophosphate dehydrogenase 0.0505 1 0.5
Trypanosoma cruzi inosine-5'-monophosphate dehydrogenase, putative 0.0505 1 0.5
Toxoplasma gondii IMP dehydrogenas 0.0505 1 0.5
Plasmodium falciparum inosine-5'-monophosphate dehydrogenase 0.0475 0.9144 0.5
Mycobacterium ulcerans inosine 5'-monophosphate dehydrogenase 0.0505 1 1
Echinococcus granulosus inosine 5' monophosphate dehydrogenase 2 0.0505 1 1

Activities

Activity type Activity value Assay description Source Reference
CLH (ADMET) = 24 uL/min Intrinsic clearance in human liver microsomes assessed per mg of protein ChEMBL. 23879463
CLH (ADMET) = 24 uL/min Intrinsic clearance in human liver microsomes measured per gram of protein at 200 uM measured after 1 by LC/MS/MS method ChEMBL. 23795283
EC50 (binding) = 9 nM Inhibition of DOT1L (unknown origin)-mediated H3K79 methylation by cell based assay ChEMBL. 23879463
EC50 (functional) = 0.004 uM Antiproliferative activity against human THP1 cells containing MLL-AF9 ChEMBL. 23879463
EC50 (functional) = 8.1 uM Cytotoxicity against human THP1 cells harboring MLL-AF9 oncogene after 20 days by XTT assay ChEMBL. 22924785
EC50 (functional) = 101 uM Cytotoxicity against human NB4 cells harboring wild type MLL oncogene after 20 days by XTT assay ChEMBL. 22924785
GI (functional) = 91.7 % Cytotoxicity against human MV4-11 cells harboring MLL-AF4 oncogene assessed as growth inhibition at 10 uM measured on day 20 by XTT assay ChEMBL. 22924785
IC50 (functional) = 0.2 uM Induction of histone methylation in human MV4-11 cells assessed as H3K79 methylation after 4 days by Western blot analysis ChEMBL. 23795283
Kd (binding) = 0.066 uM Binding affinity at human recombinant DOT1L catalytic domain amino acid (1 to 472)-nucleosome complex by isothermal titration calorimetric assay ChEMBL. 22924785
Kd (binding) = 0.073 uM Competitive inhibition of human recombinant DOT1L catalytic domain amino acid (1 to 472)-nucleosome complex by isothermal titration calorimetric assay in presence of 1 uM of SAH ChEMBL. 22924785
Kd (binding) = 0.13 uM Competitive inhibition of human recombinant DOT1L catalytic domain amino acid (1 to 472)-nucleosome complex by isothermal titration calorimetric assay in presence of 2.5 uM of SAH ChEMBL. 22924785
Kd (binding) = 0.17 uM Binding affinity at human recombinant DOT1L catalytic domain amino acid (1 to 472) by isothermal titration calorimetric assay ChEMBL. 22924785
Kd (binding) = 0.2 uM Competitive inhibition of human recombinant DOT1L catalytic domain amino acid (1 to 472)-nucleosome complex by isothermal titration calorimetric assay in presence of 5 uM of SAH ChEMBL. 22924785
Kd (binding) = 0.24 uM Competitive inhibition of human recombinant DOT1L catalytic domain amino acid (1 to 472)-nucleosome complex by isothermal titration calorimetric assay in presence of 10 uM of SAH ChEMBL. 22924785
Kd (binding) = 0.55 uM Competitive inhibition of human recombinant DOT1L catalytic domain amino acid (1 to 472)-nucleosome complex by isothermal titration calorimetric assay in presence of 20 uM of SAH ChEMBL. 22924785
Ki (binding) = 0.5 nM Competitive inhibition of recombinant human DOT1L using adenosine/deazaadenosine as substrate and SAM cofactor ChEMBL. 23879463
Ki (binding) = 0.00046 uM Inhibition of human recombinant DOT1L catalytic domain amino acid (1 to 472) using [3H]-SAM after 30 mins by scintillation counter ChEMBL. 22924785
Ki (binding) = 0.00072 uM Inhibition of human recombinant DOT1L (catalytic domain 1 to 472) using [3H]-SAM by scintillation containing ChEMBL. 23795283
Ki (binding) > 50 uM Inhibition of SUV39H1 (unknown origin) ChEMBL. 23795283
Ki (binding) > 50 uM Inhibition of CARM1 (unknown origin) ChEMBL. 23795283
Ki (binding) > 50 uM Inhibition of PRMT1 (unknown origin) ChEMBL. 23795283
Ki (binding) > 100 uM Inhibition of SUV39H1 ChEMBL. 22924785
Ki (binding) > 100 uM Inhibition of CARM1 ChEMBL. 22924785
Ki (binding) > 100 uM Inhibition of PRMT1 ChEMBL. 22924785

Phenotypes

Whole-cell/tissue/organism interactions

Species name Source Reference Is orphan
Homo sapiens ChEMBL23 22924785

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

3 literature references were collected for this gene.

If you have references for this compound, please enter them in a user comment (below) or Contact us.