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Compound Detail

CHEMBL2441082

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COc1cc2c(NC3CCN(C(C)C)CC3)nc(N3CCC(F)(F)CC3)nc2cc1OCCCN1CCCC1

Basic Information

ChEMBL ID CHEMBL2441082
Phase Preclinical
Structure Type MOL
InChI Key RNAMYOYQYRYFQY-UHFFFAOYSA-N
23
Targets
55
Activities
4
Assay Types
7
PK Parameters
20
Publications
0
Known Names

Molecular Properties

546.7
MW (Da)
5.02
ALogP
8
HBA
1
HBD
66.0
PSA (Ų)
0.42
QED
2
Ro5 Violations
10
Rot. Bonds

Drug Information

Molecule Type Small molecule
Availability Unknown
Chirality Unknown

Flags

First in Class Prodrug Chemical Probe

Extended Properties

Molecular Formula C29H44F2N6O2
MW 546.71
Aromatic Rings 2
Heavy Atoms 39
NP-Likeness -1.24

Activity Summary

IC50 43 meas. best 9.29
Ki 6 meas. best 8.43
EC50 4 meas. best 5.46
Kd 2 meas. best 7.21

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Histone-lysine N-methyltransferase EHMT2
CHEMBL6032
IC50 9.29 7.3725 0.5 8
Histone-lysine N-methyltransferase EHMT1
CHEMBL6031
IC50 8.55 7.4233 2.8 3
Histone-lysine N-methyltransferase EHMT2
CHEMBL6032
Ki 8.43 8.43 3.7 1
Histamine H3 receptor
CHEMBL264
Ki 7.35 7.35 45.0 2
Histone-lysine N-methyltransferase EHMT1
CHEMBL6031
Kd 7.21 7.21 62.0 1
Histone-lysine N-methyltransferase EHMT2
CHEMBL6032
Kd 6.64 6.64 230.0 1
Unchecked
CHEMBL612545
Ki 6.05 6.05 900.0 1
K562
CHEMBL385
IC50 6.04 6.04 920.0 1
MDA-MB-231
CHEMBL400
IC50 6.0 5.7425 990.0 4
HT-29
CHEMBL384
IC50 5.87 5.87 1350.0 1
FLC clone 745
CHEMBL6066809
IC50 5.8 5.8 1600.0 1
HeLa
CHEMBL399
IC50 5.76 5.76 1740.0 1
HepG2
CHEMBL395
IC50 5.57 5.57 2690.0 1
A-375
CHEMBL613859
IC50 5.51 5.51 3062.0 1
L02
CHEMBL4296457
IC50 5.49 5.325 3230.0 2
A-431
CHEMBL614069
IC50 5.47 5.47 3380.0 1
PANC-1
CHEMBL614139
EC50 5.46 5.46 3500.0 1
Alpha-1D adrenergic receptor
CHEMBL223
Ki 5.35 5.35 4500.0 2
HCT-116
CHEMBL394
IC50 5.3 5.3 5010.0 1
Histone-lysine N-methyltransferase EZH2
CHEMBL2189110
IC50 5.3 5.3 5000.0 1
PANC-1
CHEMBL614139
IC50 5.24 5.24 5740.0 1
JJN-3
CHEMBL4296444
IC50 5.23 4.9675 5850.0 4
U2OS
CHEMBL615023
EC50 5.22 5.22 6000.0 1
Unchecked
CHEMBL612545
IC50 5.16 4.77 6910.0 4
PC-3
CHEMBL390
EC50 5.05 5.05 8900.0 1
KMS-12-BM
CHEMBL4296455
IC50 4.97 4.6275 10800.0 4
SARS-CoV-2
CHEMBL4303835
IC50 4.78 4.78 16730.0 2
MDA-MB-231
CHEMBL400
EC50 4.78 4.78 16700.0 1
RPMI-8226
CHEMBL614882
IC50 4.66 4.615 22000.0 2

Pharmacokinetic Data

Parameter Value Units Species
AUC 412.0 ng.hr.mL-1 Mus musculus
AUC 1265.0 ng.hr.mL-1 Mus musculus
AUC 1265.09 ng.hr.mL-1 Mus musculus
CL 0.5 mL.min-1.g-1 Mus musculus
Cmax 124.38 nM Mus musculus
Cmax 1732.18 nM Mus musculus
T1/2 1.5 hr Mus musculus

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Histone-lysine N-methyltransferase EHMT2 IC50 = 0.51 nM 9.29 Inhibition of G9a (unknown origin) by AlphaLISA assay 37268593
Histone-lysine N-methyltransferase EHMT1 IC50 = 2.8 nM 8.55 Inhibition of GLP (unknown origin) 34847495
Histone-lysine N-methyltransferase EHMT2 Ki = 3.7 nM 8.43 Non-competitive inhibition of lysine methyltransferase G9a (unknown origin) usin... 24102134
Histone-lysine N-methyltransferase EHMT2 IC50 = 11.97 nM 7.92 Inhibition of human recombinant G9a (785 to 1210 residues) using Histone H3 and ... 37974951
Histone-lysine N-methyltransferase EHMT2 IC50 = 40.0 nM 7.4 Inhibition of lysine methyltransferase G9a in human PANC1 cells assessed as redu... 24102134
Histamine H3 receptor Ki = 45.0 nM 7.35 Selectivity interaction (Enzyme panel (GPCRS, ion channels, and transporters)) E... -
Histamine H3 receptor Ki = 45.0 nM 7.35 Binding affinity to histamine H3 receptor (unknown origin) by radioligand bindin... 24102134
Histone-lysine N-methyltransferase EHMT1 Kd = 62.0 nM 7.21 Binding affinity to human GLP (982 to 1266 residues) assessed as dissociation co... 35763668
Histone-lysine N-methyltransferase EHMT1 IC50 = 106.0 nM 6.97 Affinity Phenotypic Cellular interaction (Immunofluorescence in-cell Western (re... -
Histone-lysine N-methyltransferase EHMT2 IC50 = 106.0 nM 6.97 Affinity Phenotypic Cellular interaction (Immunofluorescence in-cell Western (re... -
Histone-lysine N-methyltransferase EHMT2 IC50 = 110.0 nM 6.96 Inhibition of lysine methyltransferase G9a in human MDA-MB-231 cells assessed as... 24102134
Histone-lysine N-methyltransferase EHMT2 IC50 = 130.0 nM 6.89 Inhibition of lysine methyltransferase G9a in human PC3 cells assessed as reduct... 24102134
Histone-lysine N-methyltransferase EHMT2 IC50 = 130.0 nM 6.89 Inhibition of lysine methyltransferase G9a in human U2OS cells assessed as reduc... 24102134
Histone-lysine N-methyltransferase EHMT1 IC50 = 180.0 nM 6.75 Inhibition of human GLP (982 to 1266 residues) using H3 peptide as substrate mea... 35763668
Histone-lysine N-methyltransferase EHMT2 IC50 = 220.0 nM 6.66 Inhibition of human G9a (913 to 1193 residues) using H3 peptide as substrate mea... 35763668
Histone-lysine N-methyltransferase EHMT2 Kd = 230.0 nM 6.64 Binding affinity to human G9a (913 to 1193 residues) assessed as dissociation co... 35763668
Unchecked Ki = 900.0 nM 6.05 Binding affinity to sigma 2 receptor (unknown origin) by radioligand binding ass... 24102134
K562 IC50 = 920.0 nM 6.04 Antiproliferative activity against human K562 cells measured after 72 hrs by MTT... 34847495
MDA-MB-231 IC50 = 990.0 nM 6.0 Antiproliferative activity against human MDA-MB-231 cells incubated for 3 to 5 d... 37788550
MDA-MB-231 IC50 = 1003.0 nM 6.0 Antiproliferative activity against human MDA-MB-231 cells after 5 days by MTT as... 37788550

Literature References

PubMed DOI Target Context # Activities
- 10.6019/CHEMBL4689842 HEK-293T 345
- 10.6019/CHEMBL4689842 U2OS 344
- 10.6019/CHEMBL4689842 Fibroblast 344
31804189 10.18632/aging.102558 Mus musculus 30
32552834 10.1186/s13148-020-00879-5 Unchecked 28
32015216 10.18632/aging.102750 A-375 22
32015216 10.18632/aging.102750 M14 18
- 10.6019/CHEMBL5674860 Colon cancer organoid 12
- 10.6019/CHEMBL5724558 Colon cancer organoid 12
32015216 10.18632/aging.102750 Histone-lysine N-methyltransferase EHMT2 10
31775874 10.1186/s13148-019-0758-2 Olaparib-resistant PEO1 8
37788550 10.1016/j.ejmech.2023.115841 MDA-MB-231 8
32477831 10.1186/s40164-020-00164-4 Histone-lysine N-methyltransferase EHMT2 7
32477831 10.1186/s40164-020-00164-4 JJN-3 6
- 10.6019/CHEMBL4495565 SARS-CoV-2 6
32477831 10.1186/s40164-020-00164-4 KMS-12-BM 6
24102134 10.1021/jm401480r Histone-lysine N-methyltransferase EHMT2 6
- 10.6019/CHEMBL5608141 Colon cancer organoid 6
- 10.1158/2159-8290.CD-23-0050 Colon cancer organoid 5
24102134 10.1021/jm401480r Unchecked 5

Data from ChEMBL 36 via Core Engine