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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 public 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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