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DNL343 | DNL343 : Activator of EIF2B2
RATINGS:
Cellular Use: (1 reviews)

In Model Organisms: (1 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
EIF2B2
    • IC50:9.8 nM
    • IC50:12.46 nM
    Activator
    10 nM - 3 µM

    Selectivity

    In Vitro Selectivity Assessment
    Potency Assay Off-Target:
    CEREP and kinase panel assays
    Selectivity Assessment Description:
    No significant hits in CEREP and Kinase assay panels

    Potency
    Cellular
    In Vitro

    EIF2B2

    Mode of Action: Activator

    Structure-Activity-Relationship data available? Yes

    DOI Reference: 10.1021/acs.jmedchem.3c02422

    In Vivo Validations

    Rat
    Dose: 1 mg/kg
    Route of delivery: Intravenous
    Plasma half life: 12.5 hr
    Systemic clearance: 0.4 mL/min/kg
    Bioavailability: 65% (3 mg/kg PO dose)
    Volume of Distribution at Steady-State: 0.31 L/kg

    DOI Reference: 10.1021/acs.jmedchem.3c02422

    Dog
    Dose: 0.5 mg/kg
    Route of delivery: Intravenous
    Plasma half life: 7.4 hr
    Systemic clearance: 4.8 mL/min/kg
    Bioavailability: >99% (1 mg/kg PO dose)
    Volume of Distribution at Steady-State: 2.7 L/kg

    DOI Reference: 10.1021/acs.jmedchem.3c02422

    Monkey (Cynomolgus)
    Dose: 0.5 mg/kg
    Route of delivery: Intravenous
    Plasma half life: 7.6 hr
    Systemic clearance: 2.9 mL/min/kg
    Bioavailability: >99% (1 mg/kg PO dose)
    Volume of Distribution at Steady-State: 1.9 L/kg

    DOI Reference: 10.1021/acs.jmedchem.3c02422

    Chemical Information

    Molecular Formula C20H19ClF3N3O4
    SMILEs O=C(COc1ccc(Cl)cc1)NC12CC(c3nnc(C4CC(OC(F)(F)F)C4)o3)(C1)C2
    InChI InChI=1S/C20H19ClF3N3O4/c21-12-1-3-13(4-2-12)29-7-15(28)25-19-8-18(9-19,10-19)17-27-26-16(30-17)11-5-14(6-11)31-20(22,23)24/h1-4,11,14H,5-10H2,(H,25,28)
    Molecular weight 457.10 Da
    AlogP 0.0
    HBond acceptors 7
    HBond donors 1
    Atoms 50

    Vendors

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    Expert Reviews

    by SERP
    (on 31 May 2024)
    Cellular Use Rating
    In Model Organisms
    Upon detection of cellular stress, eIF2a becomes phosphorylated. p-eIF2a inhibits the GEF activity of eIF2B, resulting in activation of the integrated stress response (ISR) and stalled protein translation....
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