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Compound Detail

CHEMBL3087498

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CC(C)N(CCCNC(=O)Nc1ccc(C(C)(C)C)cc1)C[C@H]1O[C@@H](n2cc(Br)c3c(N)ncnc32)[C@H](O)[C@@H]1O

Basic Information

ChEMBL ID CHEMBL3087498
Phase Preclinical
Structure Type MOL
InChI Key IQCKJUKAQJINMK-HUBRGWSESA-N
4
Targets
16
Activities
3
Assay Types
0
PK Parameters
20
Publications
0
Known Names

Molecular Properties

618.6
MW (Da)
3.61
ALogP
9
HBA
5
HBD
150.8
PSA (Ų)
0.23
QED
1
Ro5 Violations
9
Rot. Bonds

Drug Information

Molecule Type Small molecule
Availability Unknown
Chirality Unknown

Flags

First in Class Prodrug Chemical Probe

Extended Properties

Molecular Formula C28H40BrN7O4
MW 618.58
Aromatic Rings 3
Heavy Atoms 40
NP-Likeness -0.70

Activity Summary

IC50 11 meas. best 9.52
Kd 4 meas. best 10.25
EC50 1 meas. best 8.05

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Histone-lysine N-methyltransferase, H3 lysine-79 specific
CHEMBL1795117
Kd 10.25 10.23 0.1 3
Histone-lysine N-methyltransferase, H3 lysine-79 specific
CHEMBL1795117
IC50 9.52 9.042 0.3 5
DNA (cytosine-5)-methyltransferase 1
CHEMBL1993
IC50 9.52 9.52 0.3 1
Unchecked
CHEMBL612545
IC50 8.58 7.3233 2.6 3
Histone-lysine N-methyltransferase, H3 lysine-79 specific
CHEMBL1795117
EC50 8.05 8.05 9.0 1
Unchecked
CHEMBL612545
Kd 5.2 5.2 6300.0 1
NCI-H460
CHEMBL396
IC50 5.05 4.745 8830.0 2

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Histone-lysine N-methyltransferase, H3 lysine-79 specific Kd = 0.0561 nM 10.25 Binding affinity to recombinant N-terminal DOT1L (1 to 420 residues) (unknown or... 23250418
Histone-lysine N-methyltransferase, H3 lysine-79 specific Kd = 0.06 nM 10.22 Binding affinity to DOT1L (unknown origin) by surface plasmon resonance analysis 25406853
Histone-lysine N-methyltransferase, H3 lysine-79 specific Kd = 0.06 nM 10.22 Binding affinity to recombinant N-terminal DOT1L (1 to 420 residues) (unknown or... 23250418
Histone-lysine N-methyltransferase, H3 lysine-79 specific IC50 = 0.3 nM 9.52 Competitive inhibition of recombinant human DOT1L using adenosine/deazaadenosine... 23879463
DNA (cytosine-5)-methyltransferase 1 IC50 = 0.3 nM 9.52 Inhibition of DNMT1 (unknown origin) 27485386
Histone-lysine N-methyltransferase, H3 lysine-79 specific IC50 = 0.3 nM 9.52 Affinity Biochemical interaction (Radioactive enzyme assay) EUB0000216b DOT1L -
Histone-lysine N-methyltransferase, H3 lysine-79 specific IC50 = 0.3 nM 9.52 Inhibition of recombinant N-terminal DOT1L (1 to 420 residues) (unknown origin) ... 23250418
Histone-lysine N-methyltransferase, H3 lysine-79 specific IC50 = 2.6 nM 8.59 Affinity On-target Cellular interaction (Western Blot (reduction of H3K79 dimeth... -
Unchecked IC50 = 2.65 nM 8.58 Downregulation of H3K79 methylation in human A-431 cells incubated for 3 to 4 da... 23250418
Histone-lysine N-methyltransferase, H3 lysine-79 specific IC50 = 8.8 nM 8.06 Inhibition of DOT1L in human MCF10A cells assessed as reduction of H3K79 level 25406853
Unchecked IC50 = 8.8 nM 8.06 Downregulation of H3K79 methylation in human MCF-10A cells by fluorescence micro... 23250418
Histone-lysine N-methyltransferase, H3 lysine-79 specific EC50 = 9.0 nM 8.05 Inhibition of DOT1L (unknown origin)-mediated H3K79 methylation by cell based as... 23879463
Unchecked IC50 = 4700.0 nM 5.33 Inhibition of Clostridioides difficile-specific DNA adenine methyltransferase PD... 36581322
Unchecked Kd = 6300.0 nM 5.2 Binding affinity to Clostridioides difficile-specific DNA adenine methyltransfer... 36581322
NCI-H460 IC50 = 8830.0 nM 5.05 Antiproliferative activity against human NCI-H460 cells harboring wildtype DOT1L... 39255403
NCI-H460 IC50 = 36010.0 nM 4.44 Antiproliferative activity against human NCI-H460 cells harboring DOT1L R231Q mu... 39255403

Literature References

PubMed DOI Target Context # Activities
30171029 10.3324/haematol.2018.191262 Unchecked 274
30171029 10.3324/haematol.2018.191262 RPMI-8226 26
30171029 10.3324/haematol.2018.191262 MM1.S 24
23250418 10.1038/ncomms2304 Unchecked 17
- 10.6019/CHEMBL5724558 Colon cancer organoid 12
- 10.6019/CHEMBL5674860 Colon cancer organoid 12
- 10.6019/CHEMBL4689842 U2OS 9
30171029 10.3324/haematol.2018.191262 KMS-12-PE 8
- 10.6019/CHEMBL4689842 Fibroblast 7
- 10.6019/CHEMBL4689842 HEK-293T 6
- 10.6019/CHEMBL5608141 Colon cancer organoid 6
30171029 10.3324/haematol.2018.191262 KMS-12-BM 5
- 10.1158/2159-8290.CD-23-0050 Colon cancer organoid 5
23250418 10.1038/ncomms2304 Histone-lysine N-methyltransferase, H3 lysine-79 specific 5
- 10.6019/CHEMBL4495565 SARS-CoV-2 4
33691794 10.1186/s13148-021-01037-1 A549 4
36581322 10.1021/acs.jmedchem.2c01789 Unchecked 3
30171029 10.3324/haematol.2018.191262 U-266 3
- 10.6019/CHEMBL4808148 Histone deacetylase 6 2
25406853 10.1021/jm501234a Histone-lysine N-methyltransferase, H3 lysine-79 specific 2

Data from ChEMBL 36 via Core Engine