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RO4938581 | RO4938581 : Negative Allosteric Modulator of GABRA5
RATINGS:
Cellular Use: (1 reviews)

In Model Organisms: (1 reviews)
Probe Summary
Selectivity
Potency
In Vivo
Control Compounds
Chemical Information
References
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Probe Summary

Targets Biochemical/Biophysical Potency Cellular Potency
GABRA5
  • Ki:4.65 ± 0.79 nM
  • IC50:7.4 nM
Negative Allosteric
up to 1 uM

Selectivity

In Vitro Selectivity Assessment
Selectivity Assessment Description:
Selectivity within family: Radioligand competition displacement assay: GABRA1 (α1β3γ2): rat (Ki = 17 ...
In Vitro Selectivity Assessment
Selectivity Assessment Description:
Roche CEREP panel (82 targets) at 10 µM: clean; Kinase panel (468 kinases) at 10 µM: clean with clos ...

Potency
Cellular
In Vitro

GABRA5

Mode of Action: Negative Allosteric

Structure-Activity-Relationship data available? Yes

DOI Reference: 10.1016/j.bmcl.2009.08.053

In Vivo Validations

Rat
Dose: 0.3 to 3 mg/kg
Route of delivery: Intravenous, Oral
Plasma half life: 4.9 h
Systemic clearance: 2.9 mL/min/Kg
Bioavailability: 89%
Volume of Distribution at Steady-State: 1.2 L/Kg
Target engagement assay: Brain/plasma ratio 0.4

DOI Reference: 10.1016/j.bmcl.2009.08.053

Dose: 0.1 mg/Kg
Route of delivery: Intravenous
Plasma half life: 2.3 ± 0.12 h
Systemic clearance: 0.070 ± 0.004 L/h/Kg
Cmax: 618 ± 27 ng/mL
Area Under the Curve:: 1555 ± 87 ng/ml × h
Volume of Distribution at Steady-State: 0.22 ± 0.01 L/Kg

DOI Reference: 10.1016/j.bcp.2013.02.004

Dose: 0.1 mg/Kg
Route of delivery: Oral
Plasma half life: 2.9 ± 0.24 h
Systemic clearance: 0.066 ± 0.004 L/h/Kg
Cmax: 290 ± 39 ng/mL
Tmax: 1.1 ± 0.23 h
Area Under the Curve:: 1535 ± 93 ng/ml × h

DOI Reference: 10.1016/j.bcp.2013.02.004

Negative Control Compounds

RO4991571
Notes: RO4991571: Radioligand competition displacement assay (recombinant rat GABAA subtypes expressed in HEK293 cells): GABRA5 (α5β3γ2), GABRA1 (α1β3γ2): both Ki > 3.16 µM
SMILES: Cc1c2Cn3c(c4ccc(cc4n2cn1)[Br])ncn3

Chemical Information

Molecular Formula C13H8BrF2N5
SMILEs FC(F)c1ncn2c1Cn1ncnc1-c1cc(Br)ccc1-2
InChI InChI=1S/C13H8BrF2N5/c14-7-1-2-9-8(3-7)13-17-5-19-21(13)4-10-11(12(15)16)18-6-20(9)10/h1-3,5-6,12H,4H2
Molecular weight 350.99 Da
AlogP 3.1926000000000014
HBond acceptors 5
HBond donors --
Atoms 29

Expert Reviews

by SERP
(on 27 Nov 2025 )
Cellular Use Rating
In Model Organisms
RO4938581 is a highly potent and reasonably selective GABAA alpha5 inverse agonist with a full molecular profiling dataset. The SAR is described, and negative controls can be selected from the described...
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