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Compound Detail

CHEMBL4542380

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O=C(NC[C@H](O)CN1CCc2ccccc2C1)c1ccnc(NC2CCC2)c1

Basic Information

ChEMBL ID CHEMBL4542380
Phase Preclinical
Structure Type MOL
InChI Key TWKYXZSXXXKKJU-FQEVSTJZSA-N
5
Targets
60
Activities
3
Assay Types
0
PK Parameters
20
Publications
0
Known Names

Molecular Properties

380.5
MW (Da)
2.19
ALogP
5
HBA
3
HBD
77.5
PSA (Ų)
0.69
QED
0
Ro5 Violations
7
Rot. Bonds

Drug Information

Molecule Type Unknown
Availability Unknown
Chirality Unknown

Flags

First in Class Prodrug Chemical Probe

Extended Properties

Molecular Formula C22H28N4O2
MW 380.49
Aromatic Rings 2
Heavy Atoms 28
NP-Likeness -1.26

Activity Summary

IC50 44 meas. best 8.52
EC50 11 meas. best 8.68
Ki 5 meas. best 8.62

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Protein arginine N-methyltransferase 5
CHEMBL1795116
EC50 8.68 7.965 2.1 2
PRMT5/MEP50 complex
CHEMBL3137261
Ki 8.62 8.204 2.4 5
Protein arginine N-methyltransferase 5
CHEMBL1795116
IC50 8.52 8.1386 3.0 7
PRMT5/MEP50 complex
CHEMBL3137261
IC50 8.4 8.0383 4.0 6
Unchecked
CHEMBL612545
EC50 8.15 6.705 7.0 8
Unchecked
CHEMBL612545
IC50 7.3 5.9004 50.0 26
Z-138
CHEMBL4483276
IC50 7.21 7.21 62.0 1
G411
CHEMBL6066763
EC50 7.0 7.0 100.0 1

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Protein arginine N-methyltransferase 5 EC50 = 2.1 nM 8.68 Inhibition of PRMT5 in human Z138 cells assessed as effect on SDMA level incubat... 29946150
PRMT5/MEP50 complex Ki = 2.4 nM 8.62 Inhibition of Flag-tagged human PRMT5/his-tagged MEP50 (unknown origin) expresse... 29946150
PRMT5/MEP50 complex Ki = 2.8 nM 8.55 Inhibition of Flag-tagged human PRMT5/his-tagged MEP50 (unknown origin) expresse... 29946150
Protein arginine N-methyltransferase 5 IC50 = 3.0 nM 8.52 Inhibition of PRMT5 in human Z138 cells assessed as reduction in symmetrical dim... 26985292
Protein arginine N-methyltransferase 5 IC50 = 3.0 nM 8.52 Affinity On-target Cellular interaction (In-Cell Western (ICW) format assay (inh... -
PRMT5/MEP50 complex Ki = 3.1 nM 8.51 Inhibition of Flag-tagged human PRMT5/his-tagged MEP50 (unknown origin) expresse... 29946150
Protein arginine N-methyltransferase 5 IC50 = 4.0 nM 8.4 Affinity Biochemical interaction: (inhibition of methyl group transfer to biotin... -
PRMT5/MEP50 complex IC50 = 4.0 nM 8.4 Inhibition of human full length FLAG-tagged PRMT5/human His6-tagged MEP50 expres... 26985292
Protein arginine N-methyltransferase 5 IC50 = 4.0 nM 8.4 Affinity Biochemical interaction (HTRF assay (monomethylation of H4R3 on a histo... -
PRMT5/MEP50 complex IC50 = 4.8 nM 8.32 Inhibition of Flag-tagged human PRMT5/his-tagged MEP50 (unknown origin) expresse... 29946150
PRMT5/MEP50 complex IC50 = 5.5 nM 8.26 Inhibition of Flag-tagged human PRMT5/his-tagged MEP50 (unknown origin) expresse... 29946150
PRMT5/MEP50 complex IC50 = 6.1 nM 8.21 Inhibition of Flag-tagged human PRMT5/his-tagged MEP50 (unknown origin) expresse... 29946150
Unchecked EC50 = 7.0 nM 8.15 Antiproliferative activity against human HF5205 cells incubated for 9 to 12 days... 33579912
PRMT5/MEP50 complex Ki = 9.8 nM 8.01 Inhibition of Flag-tagged human PRMT5/his-tagged MEP50 (unknown origin) expresse... 29946150
Protein arginine N-methyltransferase 5 IC50 = 11.0 nM 7.96 Inhibition of PRMT5 (unknown origin) assessed as inhibition of PRMT5/MEP50 compl... 29065155
Protein arginine N-methyltransferase 5 IC50 = 11.0 nM 7.96 Affinity Biochemical interaction: (enzymatic radioactive assay) EUB0000198b PRMT... -
PRMT5/MEP50 complex IC50 = 19.6 nM 7.71 Inhibition of Flag-tagged human PRMT5/his-tagged MEP50 (unknown origin) expresse... 29946150
PRMT5/MEP50 complex Ki = 46.3 nM 7.33 Inhibition of Flag-tagged human PRMT5/his-tagged MEP50 (unknown origin) expresse... 29946150
PRMT5/MEP50 complex IC50 = 46.3 nM 7.33 Inhibition of Flag-tagged human PRMT5/his-tagged MEP50 (unknown origin) expresse... 29946150
Unchecked EC50 = 50.0 nM 7.3 Antiproliferative activity against human G752 cells incubated for 9 to 12 days b... 33579912

Literature References

PubMed DOI Target Context # Activities
33579912 10.1038/s41467-021-21204-5 Unchecked 49
29946150 10.1038/s41598-018-28002-y Protein arginine N-methyltransferase 5 24
29946150 10.1038/s41598-018-28002-y Unchecked 24
30026560 10.1038/s41467-018-04863-9 Protein arginine N-methyltransferase 5 13
27270440 10.1038/onc.2016.205 Protein arginine N-methyltransferase 5 13
- 10.6019/CHEMBL5674860 Colon cancer organoid 12
- 10.6019/CHEMBL5724558 Colon cancer organoid 12
29946150 10.1038/s41598-018-28002-y PRMT5/MEP50 complex 10
- 10.6019/CHEMBL4689842 U2OS 10
- 10.6019/CHEMBL4689842 Fibroblast 8
33579912 10.1038/s41467-021-21204-5 Protein arginine N-methyltransferase 5 7
31665911 10.1177/0963689719885083 A549 7
29065155 10.1371/journal.pone.0186982 Protein arginine N-methyltransferase 5 6
29441724 10.1002/cam4.1360 Protein arginine N-methyltransferase 5 6
- 10.6019/CHEMBL5608141 Colon cancer organoid 6
33579912 10.1038/s41467-021-21204-5 G411 6
29441724 10.1002/cam4.1360 Unchecked 6
- 10.1158/2159-8290.CD-23-0050 Colon cancer organoid 5
27270440 10.1038/onc.2016.205 A549 5
33691794 10.1186/s13148-021-01037-1 A549 4

Data from ChEMBL 36 via Core Engine