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ICENTICAFTOR | ICENTICAFTOR : Potentiator of CFTR
RATINGS:
Cellular Use: (2 reviews)

In Model Organisms: (2 reviews)
Probe Summary
Selectivity
Potency
In Vivo
Control Compounds
Chemical Information
References
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Probe Summary

Targets Biochemical/Biophysical Potency Cellular Potency
CFTR (Mutant:F508del, G551D, WT)
    • EC50:79 nM
    • EC50:47 nM
    • EC50:39 nM
    Potentiator
    up to 1 uM

    Selectivity

    Potency
    Cellular
    In Vitro

    CFTR (Mutant:F508del, G551D, WT)

    Mode of Action: Potentiator

    Structure-Activity-Relationship data available? Yes

    DOI Reference: 10.1021/acs.jmedchem.1c00343

    In Vivo Validations

    Rat
    Dose: 1 mg/Kg IV, 3 mg/Kg PO
    Route of delivery: Intravenous, Oral
    Plasma half life: 10.2 h MRT
    Systemic clearance: 5 mL/min/kg
    Cmax: 1364 nM
    Area Under the Curve:: 20635 nM/h/L
    Fb : 90.3%
    Bioavailability: 90% PO
    Volume of Distribution at Steady-State: 3.0 L/Kg

    DOI Reference: 10.1021/acs.jmedchem.1c00343

    Dog
    Dose: 0.46 mg/kg IV, 3 mg/kg PO
    Route of delivery: Intravenous, Oral
    Plasma half life: 4.4 h MRT
    Systemic clearance: 29 mL/min/Kg
    Cmax: 1952 nM PO
    Area Under the Curve:: 8670 nmol/h/L
    Fb : 94.8%
    Bioavailability: 146% PO
    Volume of Distribution at Steady-State: 7.5 L/Kh

    DOI Reference: 10.1021/acs.jmedchem.1c00343

    Monkey (Cynomolgus)
    Dose: 0.1 mg/Kg IV, 10 mg/Kg PO
    Route of delivery: Intravenous, Oral
    Plasma half life: 3.3 h MRT
    Systemic clearance: 18 mL/min/kg
    Cmax: 2303 nM PO
    Area Under the Curve:: 6780 nmol/h/L
    Fb : 88.0%
    Bioavailability: 26% PO
    Volume of Distribution at Steady-State: 3.5 L/Kg

    DOI Reference: 10.1021/acs.jmedchem.1c00343

    Chemical Information

    Molecular Formula C12H13F6N3O3
    SMILEs COc1nc(C(=O)NC[C@](C)(O)C(F)(F)F)c(N)cc1C(F)(F)F
    InChI InChI=1S/C12H13F6N3O3/c1-10(23,12(16,17)18)4-20-8(22)7-6(19)3-5(11(13,14)15)9(21-7)24-2/h3,23H,4,19H2,1-2H3,(H,20,22)/t10-/m0/s1
    Molecular weight 361.09 Da
    AlogP 1.7343
    HBond acceptors 6
    HBond donors 4
    Atoms 37

    References

    Publications

    Cross References

    canSARChEMBLBindingDB

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    Expert Reviews

    by SERP
    (on 21 Nov 2022 )
    Cellular Use Rating
    In Model Organisms
    Icenticaftor is a probe of excellent quality for both in vitro and in vivo work. As described in its original publication, it was documented to be selective for the potentiation of CFTR against a broad...
    by SERP
    (on 28 Dec 2022 )
    Cellular Use Rating
    In Model Organisms
    Icenticaftor is a high quality potentiator of both wild-type and delF508 CFTR activity. Based on profiling experiments, it appears to have high selectivity for CFTR over different GPCRs, transporters,...
    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