Detailed information for compound 1682177
Basic information
Technical information
- Name: Unnamed compound
- MW: 539.67 | Formula: C28H41N7O4
-
H donors: 5
H acceptors: 5
LogP: 2.36
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)n1ccc2c1ncnc2N
- InChi: 1S/C28H41N7O4/c1-17(2)34(13-6-12-30-27(38)33-19-9-7-18(8-10-19)28(3,4)5)15-21-22(36)23(37)26(39-21)35-14-11-20-24(29)31-16-32-25(20)35/h7-11,14,16-17,21-23,26,36-37H,6,12-13,15H2,1-5H3,(H2,29,31,32)(H2,30,33,38)/t21-,22-,23-,26-/m1/s1
- InChiKey: WXRGFPHDRFQODR-ICLZECGLSA-N
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 |
| Homo sapiens | protein arginine methyltransferase 7 | Starlite/ChEMBL | References |
Predicted pathogen targets for this compound
By orthology
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 |
|---|---|---|---|---|
| Trypanosoma brucei | protein arginine n-methyltransferase 7 | 0.0153 | 0 | 0.5 |
| Echinococcus multilocularis | histone h3 methyltransferase | 0.0155 | 1 | 1 |
| Loa Loa (eye worm) | hypothetical protein | 0.0155 | 1 | 1 |
| Trypanosoma cruzi | protein arginine n-methyltransferase 7 | 0.0153 | 0 | 0.5 |
| Trypanosoma cruzi | arginine N-methyltransferase, type III | 0.0153 | 0 | 0.5 |
| Leishmania major | arginine N-methyltransferase, type III, putative;with=GeneDB:Tb927.7.5490 | 0.0153 | 0 | 0.5 |
| Echinococcus granulosus | histone h3 methyltransferase | 0.0155 | 1 | 1 |
| Schistosoma mansoni | histone J3 methyltransferase | 0.0155 | 1 | 1 |
Activities
| Activity type | Activity value | Assay description | Source | Reference |
|---|---|---|---|---|
| Activity (functional) | = 20 % | Induction of apoptosis in human MOLM13 cells at 4 times EC50 by annexin-V staining | ChEMBL. | 23879463 |
| 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 MV4-11 cells containing MLL-AF4 | ChEMBL. | 23879463 |
| IC50 (binding) | = 0.4 nM | Inhibition of human recombinant DOT1L using [3H]-SAM as substrate after 30 mins | ChEMBL. | 22975593 |
| IC50 (binding) | = 0.4 nM | Competitive inhibition of human recombinant DOT1L (1 to 416 amino acid residues) using [3H]-SAM assessed as inhibition of nucleosome methylation incubated for 30 mins prior to substrate addition measured after 120 mins | ChEMBL. | 23433670 |
| IC50 (binding) | = 84 nM | Inhibition of DOT1L in human MCF10A cells assessed as reduction of H3K79 level | ChEMBL. | 25406853 |
| IC50 (binding) | = 700 nM | Inhibition of DOT1L in human MV4-11 cells assessed as downregulation of HOXA9/MEIS1 mRNA expression after 6 days by real-time PCR analysis | ChEMBL. | No reference |
| IC50 (binding) | = 700 nM | Inhibition of DOT1L in human MOLM13 cells assessed as downregulation of HOXA9/MEIS1 mRNA expression after 6 days by real-time PCR analysis | ChEMBL. | No reference |
| IC50 (binding) | = 400 pM | Inhibition of recombinant human DOT1L using chicken erythrocyte oligonucleosomes/[3H]-SAM as substrate assessed as incorporation of radioactivity into oligonucleosome preincubated for 30 mins followed by substrate addition measured after 120 mins | ChEMBL. | No reference |
| IC50 (binding) | = 400 pM | Inhibition of recombinant human DOT1L (1 to 416) using [3H]-SAM, SAM and nucleosome as substrate assessed as incorporation of radioactivity into nucleosome preincubated for 30 mins followed by substrate addition measured after 120 mins by flash plate assay | ChEMBL. | 25406853 |
| IC50 (binding) | = 7.5 uM | Inhibition of human full length PRMT7 expressed in Sf9 cells | ChEMBL. | 25893041 |
| IC50 (functional) | > 10 uM | Cytotoxicity against human Jurkat cells assessed as cell viability measured every 3 to 4 days up to 18 days by Guava Viacount assay | ChEMBL. | 25406853 |
| IC50 (binding) | > 20 uM | Inhibition of human full length PRMT5-MEP50 complex expressed in Sf9 cells | ChEMBL. | 25893041 |
| Inhibition (binding) | = 80 % | Inhibition of human full length PRMT5-MEP50 complex expressed in Sf9 cells assessed as inhibition of methylation of peptide substrate at 750 uM | ChEMBL. | 25893041 |
| Kd (binding) | = 0.25 nM | Binding affinity to DOT1L (unknown origin) by surface plasmon resonance analysis | ChEMBL. | 25406853 |
| Ki (binding) | = 0.3 nM | Competitive inhibition of recombinant human DOT1L using adenosine/deazaadenosine as substrate and SAM cofactor | ChEMBL. | 23879463 |
| Ki (binding) | = 0.3 nM | Inhibition of human recombinant DOT1L (catalytic domain 1 to 472) using [3H]-SAM by scintillation containing | ChEMBL. | 23795283 |
| Ki (binding) | = 0.3 nM | Inhibition of human DOT1L using oligo-nucleosome/[3H]-SAM as substrate preincubated for 30 mins followed by substrate addition measured after 120 mins by Morrison plot analysis | ChEMBL. | 25406853 |
| Ki (binding) | = 300 pM | Binding affinity to human DOT1L after 120 mins | ChEMBL. | 25406853 |
| Ki (binding) | = 0.3 uM | Inhibition of human recombinant DOT1L using [3H]-SAM as substrate after 30 mins | ChEMBL. | 22975593 |
Phenotypes
Whole-cell/tissue/organism interactions
| Species name | Source | Reference | Is orphan |
|---|---|---|---|
| Homo sapiens | ChEMBL23 | 23879463 |
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.
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
- ChEMBL: CHEMBL2169919
Bibliographic References
6 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.