GSK3484862 | GSK3484862 : inhibitor of DNMT1
RATINGS:
Cellular Use: (2 reviews)

In Model Organisms: (1 reviews)
Control Compounds
Vendors

Probe Summary

Targets Biochemical/Biophysical Potency Cellular Potency
DNMT1
  • IC50:230 nM
  • Activity:below 1 µM
degrader/inhibitor
80 nM for incubation times >12h
up to 1 µM

Selectivity

In Vitro Selectivity Assessment
Potency Assay Off-Target:
no inhibition of the family members DNMT3A/3L and DNMT3B/3L, or the assay coupling enzyme Gla1 when ...

Potency
Cellular
In Vitro

DNMT1

Mode of Action: degrader/inhibitor

Structure-Activity-Relationship data available? Yes

DOI Reference: 10.1093/narcan/zcad022

In Vivo Validations

Mouse
Dose: 2mg/Kg
Route of delivery: Intravenous
Plasma half life: 1.8 h
Systemic clearance: 13 mL/min/kg
Cmax: 5103 ng/mL
Area Under the Curve:: 2418 h*ng/mL (0-8h)
Volume of Distribution at Steady-State: 1.3 L/kg

DOI Reference: 10.1038/s43018-021-00249-x

Dose: 2 mg/Kg
Route of delivery: Subcutaneous
Plasma half life: 2.8 h
Cmax: 252 ng/mL
Area Under the Curve:: 921 h*ng/mL (0-8 h)

DOI Reference: 10.1038/s43018-021-00249-x

Dose: 30 mg/Kg
Route of delivery: Subcutaneous
Cmax: 5473 ng/mL
Area Under the Curve:: 15400 h*ng/mL (0-8 h)

DOI Reference: 10.1038/s43018-021-00249-x

Chemical Information

Molecular Formula C19H19N5OS
SMILEs CCc1c(C#N)c(SC(C(N)=O)c2ccccc2)nc(N(C)C)c1C#N
InChI InChI=1S/C19H19N5OS/c1-4-13-14(10-20)18(24(2)3)23-19(15(13)11-21)26-16(17(22)25)12-8-6-5-7-9-12/h5-9,16H,4H2,1-3H3,(H2,22,25)
Molecular weight 365.13 Da
AlogP 0.0
HBond acceptors 6
HBond donors 2
Atoms 45

References

Cross References

canSARBindingDB

Expert Reviews


(on 11 Mar 2024 )
Cellular Use Rating
GSK3685032 is a potent selective DNMT1 inhibitor that is competitive with the active-site loop of DNMT1 recognition of hemi-methylated DNA. Well characterized for cellular and in vivo activity.
(on 5 Apr 2024 )
Cellular Use Rating
In Model Organisms
GSK3484862 is a selective inhibitor of DNMT1 which displays potent enzymatic and cellular potency. Unlike other DNA hypomethylating agents, GSK348862 is a noncovalent inhibitor which offers the potential...
Note: The Chemical Probes Portal only endorses compounds as chemical probes for use as specific and selective modulators of the proposed target if they receive three or more (3-4) stars. Read more about our evaluation criteria