MK-4256 | MK-4256 : Antagonist of SSTR3
RATINGS:
Cellular Use: (0 reviews)

In Model Organisms: (0 reviews)
Control Compounds

Probe Summary

Targets Biochemical/Biophysical Potency Cellular Potency
SSTR3
    • IC50:0.66 nM
    • IC50:0.95 nM
    • % in:83%
    Antagonist
    100 nM

    Selectivity

    In Vitro Selectivity Assessment
    Selectivity Assessment Description:
    SSTR Subtype Selectivity of MK-4256 shows only SSTR3 as a target in both in vitro and functional ass ...

    Potency
    Cellular
    In Vitro

    SSTR3

    Mode of Action: Antagonist

    Structure-Activity-Relationship data available? Yes

    DOI Reference: 10.1021/ml300063m

    In Vivo Validations

    Mouse
    Dose: 4 mg/Kg IV, 10 mg/Kg PO
    Route of delivery: Intravenous, Oral
    Plasma half life: 1.52 h IV
    Systemic clearance: 10.1 mL/min kg IV
    Area Under the Curve:: 19.3 μM*h PO
    Bioavailability: 58% PO
    Volume of Distribution at Steady-State: 1.66 L/Kg IV
    Target engagement assay: In a mouse oGTT assay MK-4256 reduces the glucose excursion from 0.003 to 10 mg/kg in a dose-dependent manner. At 0.01, 0.1, and 1 mg/kg oral dose, MK-4256 achieved Cmax of 7, 88, and 493 nM, respectivley

    DOI Reference: 10.1021/ml300063m

    Rat
    Dose: 1 mg/Kg IV, 2 mg/Kg PO
    Route of delivery: Intravenous, Oral
    Plasma half life: 1.73 h IV
    Systemic clearance: 34.0 mL/min*kg IV
    Area Under the Curve:: 0.81 μM*h PO
    Bioavailability: 42% PO
    Volume of Distribution at Steady-State: 5.1 L/kg IV

    DOI Reference: 10.1021/ml300063m

    Dog
    Dose: 1 mg/Kg IV, 2 mg/Kg PO
    Route of delivery: Intravenous, Oral
    Plasma half life: 7.0 h IV
    Systemic clearance: 2.34 mL/min*kg IV
    Area Under the Curve:: 15.6 μM*h PO
    Bioavailability: 53% PO
    Volume of Distribution at Steady-State: 1.52 L/kg IV

    DOI Reference: 10.1021/ml300063m

    Monkey (Rheus)
    Dose: 1 mg/Kg IV, 2 mg/Kg PO
    Route of delivery: Intravenous, Oral
    Plasma half life: 7.21 h IV
    Systemic clearance: 3.09 mL/min*kg IV
    Area Under the Curve:: 14.4 μM*h PO
    Bioavailability: 65% PO
    Volume of Distribution at Steady-State: 1.74 L/kg IV

    DOI Reference: 10.1021/ml300063m

    Chemical Information

    Molecular Formula C27H23FN8O
    SMILEs Cc1nc([C@]2(c3cnn(C)c3)N[C@@H](c3nc(-c4ccc(F)cc4)c[nH]3)Cc3c2[nH]c2ccccc32)no1
    InChI InChI=1S/C27H23FN8O/c1-15-31-26(35-37-15)27(17-12-30-36(2)14-17)24-20(19-5-3-4-6-21(19)32-24)11-22(34-27)25-29-13-23(33-25)16-7-9-18(28)10-8-16/h3-10,12-14,22,32,34H,11H2,1-2H3,(H,29,33)/t22-,27-/m1/s1
    Molecular weight 494.20 Da
    AlogP 4.30092
    HBond acceptors 9
    HBond donors 3
    Atoms 60

    References

    Publications

    Cross References

    canSARChEMBLBindingDB

    Vendors

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    Expert Reviews


    No SERP comments found for MK-4256

    Probe MK-4256 is in the process of SERP review.

    Please continue to check back for new reviews and commentary.