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IRAK4-IN-28 | IRAK4-IN-28 : Inhibitor of IRAK4, IRAK1
RATINGS:
Cellular Use: (2 reviews)

In Model Organisms: (2 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
IRAK4
  • IC50:5 nM
  • Kd:0.7 nM
  • IC50:52 nM
  • IC50:~ 1000 nM
IRAK1
  • IC50:23 nM
    Inhibitor
    up to 1 uM

    Selectivity

    In Vitro Selectivity Assessment
    Potency Assay Off-Target:
    Millipore kinome selectivity for AZ1495 (%inhibition @ 0.1 μM) 275 kinase. The profile indicated (I ...

    Potency
    Cellular
    In Vitro

    IRAK4

    Mode of Action: Inhibitor

    Structure-Activity-Relationship data available? Yes

    DOI Reference: 10.1021/acs.jmedchem.7b01290

    IRAK1

    Mode of Action: Inhibitor

    Structure-Activity-Relationship data available? Yes

    DOI Reference: 10.1021/acs.jmedchem.7b01290

    In Vivo Validations

    Rat
    Dose: 2 mg/kg
    Route of delivery: Intravenous
    Plasma half life: 0.8 h
    Systemic clearance: 75 mL/min/kg
    Volume of Distribution at Steady-State: 2.1 L/Kg

    DOI Reference: 10.1021/acs.jmedchem.7b01290

    Dose: 5 mg/kg
    Route of delivery: Oral
    Plasma half life: 2.0 h
    Bioavailability: 28%

    DOI Reference: 10.1021/acs.jmedchem.7b01290

    Dog
    Dose: 1 mg/kg
    Route of delivery: Intravenous
    Plasma half life: 3.3 h
    Systemic clearance: 29 mL/min/kg
    Volume of Distribution at Steady-State: 3.0 L/Kg

    DOI Reference: 10.1021/acs.jmedchem.7b01290

    Negative Control Compounds

    CANSAR137197
    Notes: cpd 32 - trans isomer - IRAK4 Enz IC50 570 nM, IRAK4 cell IC50 3100 nM

    Orthogonal Probes def

    ZIMLOVISERTIB

    Chemical Information

    Molecular Formula C21H31N5O2
    SMILEs c1nc(N[C@H]2CC[C@H](N3CCOCC3)CC2)c2c(C3CCOCC3)c[nH]c2n1
    InChI InChI=1S/C21H31N5O2/c1-3-17(26-7-11-28-12-8-26)4-2-16(1)25-21-19-18(15-5-9-27-10-6-15)13-22-20(19)23-14-24-21/h13-17H,1-12H2,(H2,22,23,24,25)/t16-,17-
    Molecular weight 385.25 Da
    AlogP 2.9072000000000005
    HBond acceptors 7
    HBond donors 2
    Atoms 59

    References

    Publications

    Cross References

    Vendors

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    Expert Reviews

    by SERP+
    (on 22 Mar 2023 )
    Cellular Use Rating
    In Model Organisms
    IRAK4-IN-28 has a short half-life of 2 h in rat when administered orally. There is not sufficient selectivity versus CLK4 (1,6 nM) and Haspin (0,8 nM) and the authors themselves state: "We considered whether...
    by SERP+
    (on 22 Mar 2023 )
    Cellular Use Rating
    In Model Organisms
    IRK4-IN-28 is a potent IRK4 Inhibitor in vitro and an effect on down-stream phosphorylation in cells was clearly shown at the recommended concentration. However, IRK-1 was identified as an off-target which...
    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