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Compound Detail

CHEMBL2204995

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CCCc1cc(C)[nH]c(=O)c1CNC(=O)c1cc(-c2ccnc(N3CCN(C)CC3)c2)cc2c1cnn2C(C)C

Basic Information

ChEMBL ID CHEMBL2204995
Phase Preclinical
Structure Type MOL
InChI Key ULNXAWLQFZMIHX-UHFFFAOYSA-N
9
Targets
19
Activities
2
Assay Types
0
PK Parameters
20
Publications
0
Known Names

Molecular Properties

541.7
MW (Da)
4.31
ALogP
7
HBA
2
HBD
99.2
PSA (Ų)
0.34
QED
1
Ro5 Violations
8
Rot. Bonds

Drug Information

Molecule Type Small molecule
Availability Unknown
Chirality Unknown

Flags

First in Class Prodrug Chemical Probe

Extended Properties

Molecular Formula C31H39N7O2
MW 541.70
Aromatic Rings 4
Heavy Atoms 40
NP-Likeness -1.43

Activity Summary

IC50 18 meas. best 8.92
Ki 1 meas. best 8.92

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Histone-lysine N-methyltransferase EZH2
CHEMBL2189110
IC50 8.92 5.965 1.2 8
EZH2/SUZ12/EED/RBBP7/RBBP4
CHEMBL3301388
Ki 8.92 8.92 1.2 1
EZH2/SUZ12/EED/RBBP7/RBBP4
CHEMBL3301388
IC50 8.4 8.4 4.0 1
Histone-lysine N-methyltransferase EZH1
CHEMBL2189116
IC50 6.62 6.62 240.0 1
EZH1/SUZ12/EED/AEBP2/RBBP4 complex
CHEMBL3137287
IC50 6.62 6.62 240.0 1
FLC clone 745
CHEMBL6066809
IC50 5.66 5.66 2200.0 1
Unchecked
CHEMBL612545
IC50 5.05 5.05 9000.0 1
Alpha-1B adrenergic receptor
CHEMBL232
IC50 5.0 5.0 10000.0 1
Histone-lysine N-methyltransferase SETD7
CHEMBL5523
IC50 4.2 4.2 63000.0 1
Protein arginine N-methyltransferase 3
CHEMBL5891
IC50 4.13 4.13 74000.0 1

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Histone-lysine N-methyltransferase EZH2 IC50 = 1.2 nM 8.92 Inhibition of EZH2 (unknown origin) 35014841
EZH2/SUZ12/EED/RBBP7/RBBP4 Ki = 1.2 nM 8.92 Inhibition of PRC2 complex of FLAG-EZH2, EED, SUZ12, AEBP2 and RbAp48 using hist... 24900432
EZH2/SUZ12/EED/RBBP7/RBBP4 IC50 = 4.0 nM 8.4 Inhibition of PRC2 complex of FLAG-EZH2, EED, SUZ12, AEBP2 and RbAp48 using hist... 24900432
Histone-lysine N-methyltransferase EZH2 IC50 = 174.0 nM 6.76 Affinity On-target Cellular interaction (Immunofluorescence (inhibition of H3K27... -
Histone-lysine N-methyltransferase EZH2 IC50 = 174.0 nM 6.76 Inhibition of EZH2-mediated nuclear H3K27 methylation in human HCC1806 cells aft... 24900432
EZH1/SUZ12/EED/AEBP2/RBBP4 complex IC50 = 240.0 nM 6.62 Inhibition of PRC2 complex of EZH1, EED, SUZ12, AEBP2 and RbAp48 using histone H... 24900432
Histone-lysine N-methyltransferase EZH1 IC50 = 240.0 nM 6.62 Selectivity interaction (Methyltransferase panel (HotSpot screen, Reaction Biolo... -
FLC clone 745 IC50 = 2200.0 nM 5.66 Cytotoxicity against mouse FLC clone 745 cells assessed as reduction in cell via... 33407944
Histone-lysine N-methyltransferase EZH2 IC50 = 2900.0 nM 5.54 Inhibition of EZH2-mediated proliferation of human LNCaP cells after 6 days by c... 24900432
Histone-lysine N-methyltransferase EZH2 IC50 = 2900.0 nM 5.54 Affinity Phenotypic Cellular interaction (CellTiter-Glo assay (Promega, cell pro... -
Unchecked IC50 = 9000.0 nM 5.05 Cytotoxicity against human fetal NSC assessed as reduction in cell vaibility inc... 30559935
Alpha-1B adrenergic receptor IC50 = 10000.0 nM 5.0 Selectivity interaction (Receptors and enzyme panel (internal screening at GSK))... -
Histone-lysine N-methyltransferase EZH2 IC50 = 16000.0 nM 4.8 Inhibition of EZH2 in human BXD-1425EPN cells assessed as reduction in cell viab... 30559935
Histone-lysine N-methyltransferase EZH2 IC50 = 20000.0 nM 4.7 Inhibition of EZH2 in human DKFZ-EP1 cells assessed as reduction in cell viabili... 30559935
Histone-lysine N-methyltransferase EZH2 IC50 = 20000.0 nM 4.7 Inhibition of EZH2 in human EPN8 cells assessed as reduction in cell viability i... 30559935
Histone-lysine N-methyltransferase SETD7 IC50 = 63000.0 nM 4.2 Inhibition of SET7 using histone H3 as substrate preincubated for 10 mins follow... 24900432
Protein arginine N-methyltransferase 3 IC50 = 74000.0 nM 4.13 Inhibition of PRMT3 using histone H3 as substrate preincubated for 10 mins follo... 24900432

Literature References

PubMed DOI Target Context # Activities
30423977 10.3390/cells7110205 Histone-lysine N-methyltransferase EZH2 683
30365505 10.1371/journal.pntd.0006873 Schistosoma mansoni 66
30809307 10.7150/thno.29520 MDA-MB-231 32
30487153 10.1128/msphere.00478-18 Histone-lysine N-methyltransferase EZH2 29
30809307 10.7150/thno.29520 Unchecked 28
26030458 10.1371/journal.pone.0126466 Histone-lysine N-methyltransferase EZH2 28
30809307 10.7150/thno.29520 MDA-MB-436 28
29033304 10.1016/j.stemcr.2017.09.009 HUVEC 25
29033304 10.1016/j.stemcr.2017.09.009 Unchecked 19
24900432 10.1021/ml3003346 Unchecked 18
30559935 10.18632/oncotarget.26370 Histone-lysine N-methyltransferase EZH2 16
25203626 10.1097/cad.0000000000000166 MDA-MB-231 15
30809307 10.7150/thno.29520 MCF7 12
- 10.6019/CHEMBL5674860 Colon cancer organoid 12
- 10.6019/CHEMBL5724558 Colon cancer organoid 12
27191993 10.18632/oncotarget.9371 Histone-lysine N-methyltransferase EZH2 11
24900432 10.1021/ml3003346 Histone-lysine N-methyltransferase EZH2 10
- 10.6019/CHEMBL4689842 Fibroblast 9
30809307 10.7150/thno.29520 BT-474 9
- 10.6019/CHEMBL4689842 HEK-293T 9

Data from ChEMBL 36 via Core Engine