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BI-8668 | BI-8668 : Inhibitor of SCNN1A, SCNN1B, SCNN1G
RATINGS:
Cellular Use: (3 reviews)

In Model Organisms: (3 reviews)
Probe Summary
Selectivity
Potency
In Vivo
Control Compounds
Chemical Information
References
Vendors
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Probe Summary

Targets Biochemical/Biophysical Potency Cellular Potency
SCNN1A
    • % in:81%
    • IC50:6.2 nM
    • IC50:16.8 nM
    SCNN1B
        SCNN1G
            Inhibitor
            up to 1 uM

            Selectivity

            In Vitro Selectivity Assessment
            Potency Assay Off-Target:
            BI-8668 was tested on 50 targets in a selectivity panel and showed ≥1,000-fold selectivity for 47/50 ...

            Potency
            Cellular
            In Vitro

            SCNN1A

            Mode of Action: Inhibitor

            Structure-Activity-Relationship data available? Yes

            DOI Reference: 10.1016/j.ejmech.2023.116038

            SCNN1B

            Mode of Action: Inhibitor

            Structure-Activity-Relationship data available? Yes

            DOI Reference: 10.1016/j.ejmech.2023.116038

            SCNN1G

            Mode of Action: Inhibitor

            Structure-Activity-Relationship data available? Yes

            DOI Reference: 10.1016/j.ejmech.2023.116038

            In Vivo Validations

            Mouse
            Dose: 0.5 umol/kg
            Plasma half life: 0.39 h (MRT)
            Systemic clearance: 46 mL/min*Kg
            Volume of Distribution at Steady-State: 1.10 L/Kg

            DOI Reference: 10.1016/j.ejmech.2023.116038

            Rat
            Dose: 0.5 umol/Kg
            Plasma half life: 0.17 h (MRT)
            Systemic clearance: 59 mL/min*kg
            Cmax: 34 nM
            Tmax: 0.1 h
            Volume of Distribution at Steady-State: 0.58 L/Kg

            DOI Reference: 10.1016/j.ejmech.2023.116038

            Negative Control Compounds

            BI-0337
            Notes: IC50 > 10 µM (Ussing chamber)
            SMILES: CCn1c2cc(ccc2[n+](CC)c1CNC(c1c(N)nc(C)cn1)=O)C(N(C)CN(C)C)=O.[Cl-]

            Chemical Information

            Molecular Formula C23H32Cl2N8O2
            SMILEs CCn1c(CNC(=O)c2nc(Cl)cnc2N)[n+](CC)c2ccc(C(=O)N(C)CCN(C)C)cc21.[Cl-]
            InChI InChI=1S/C23H31ClN8O2.ClH/c1-6-31-16-9-8-15(23(34)30(5)11-10-29(3)4)12-17(16)32(7-2)19(31)14-27-22(33)20-21(25)26-13-18(24)28-20;/h8-9,12-13H,6-7,10-11,14H2,1-5H3,(H2-,25,26,27,33);1H
            Molecular weight 522.20 Da
            AlogP 0.0
            HBond acceptors 10
            HBond donors 3
            Atoms 67

            Expert Reviews

            by SERP
            (on 30 Jan 2024 )
            Cellular Use Rating
            In Model Organisms
            BI-8668 represents a good chemical probe for the endothelial sodium channel (ENaC). In Na+ transport cell-based assays it showed a low nanomolar IC50 value while the negative control compound BI-0337 showed...
            by SERP
            (on 15 Feb 2024 )
            Cellular Use Rating
            In Model Organisms
            BI-8668 is a potent (IC50 = 17 nM) and in vivo grade ENaC inhibitor with a structurally distinct scaffold from amiloride and idrevloride. At doses > 1 uM, off-target inhibition of M1/M2/M3 muscarinic receptors,...
            by SERP
            (on 22 Feb 2024 )
            Cellular Use Rating
            In Model Organisms
            Selective and cell active probe with clear in Vigo activity. Nice SAR and good inactive probe. Overall, this probe should be used to interrogate this target across assay types
            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