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MD-4251 | MD-4251 : Degrader (PROTAC) of MDM2
RATINGS:
Cellular Use: (3 reviews)

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

Targets Biochemical/Biophysical Potency Cellular Potency
MDM2
    • DC50:0.2 nM
    • Dmax:96%
    • IC50:1 nM
    Degrader (PROTAC)
    up to 30 nM

    Selectivity

    In Cell Selectivity Assessment
    Potency Assay Off-Target:
    MD-4251 was evaluated for GSPT1, IKZF1/3, and CK1α, a number of known neo-substrates for cereblon li ...
    In Cell Selectivity Assessment
    Potency Assay Off-Target:
    Cellular degradation selectivity of MD-4251 was evaluated via an unbiased proteomics analysis. MD-42 ...

    Potency
    Cellular
    In Vitro

    MDM2

    Mode of Action: Degrader (PROTAC)

    Structure-Activity-Relationship data available? Yes

    DOI Reference: 10.1021/acs.jmedchem.5c00809

    In Vivo Validations

    Mouse
    Dose: 1 mg/Kg
    Route of delivery: Intravenous
    Plasma half life: 17.6 h
    Systemic clearance: 0.576 mL/min/kg
    Area Under the Curve:: 28977 h*ng/min
    Volume of Distribution at Steady-State: 0.858 L/Kg

    DOI Reference: 10.1021/acs.jmedchem.5c00809

    Dose: 3 mg/Kg
    Route of delivery: Oral
    Plasma half life: >24 h
    Cmax: 1157 ng/mL
    Tmax: 6.67 h
    Area Under the Curve:: 20658 h·ng/mL
    Bioavailability: 38.8%

    DOI Reference: 10.1021/acs.jmedchem.5c00809

    Chemical Information

    Molecular Formula C47H53Cl2FN8O4
    SMILEs Cn1nc(C2CCC(=O)NC2=O)c2ccc(N3CCN(C[C@H]4CC[C@H](NC(=O)[C@@H]5NC6(CCCCC6)[C@@]6(C(=O)Nc7cc(Cl)ccc76)[C@H]5c5cccc(Cl)c5F)CC4)CC3)cc21
    InChI InChI=1S/C47H53Cl2FN8O4/c1-56-37-25-30(13-14-31(37)41(55-56)33-15-17-38(59)53-43(33)60)58-22-20-57(21-23-58)26-27-8-11-29(12-9-27)51-44(61)42-39(32-6-5-7-35(49)40(32)50)47(46(54-42)18-3-2-4-19-46)34-16-10-28(48)24-36(34)52-45(47)62/h5-7,10,13-14,16,24-25,27,29,33,39,42,54H,2-4,8-9,11-12,15,17-23,26H2,1H3,(H,51,61)(H,52,62)(H,53,59,60)/t27-,29-,33?,39-,42+,47+/m0/s1
    Molecular weight 882.36 Da
    AlogP 6.685000000000008
    HBond acceptors 12
    HBond donors 4
    Atoms 115

    Expert Reviews

    by SERP
    (on 8 Dec 2025 )
    Cellular Use Rating
    In Model Organisms
    The authors primarily used the RS4;11 cell line in most studies, and only cell growth inhibitory activities were evaluated in MV4-11 and MOLM-13. Therefore, attention would be required when utilizing other...
    by SERP
    (on 17 Dec 2025 )
    Cellular Use Rating
    In Model Organisms
    ( The reviewer did not leave any comments )
    by SERP
    (on 26 Jan 2026 )
    Cellular Use Rating
    In Model Organisms
    At 30 nM, MD-4251 appears to have little effect on common off-targets (GSPT1, IKZF1/3, CK1a) at a 2 hr timepoint in RS4;11 cells. A caveat is that degradation proteomics was performed only at 3 nM @2 hrs,...
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