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MD-265 | MD-265 : Degrader (PROTAC) of MDM2
RATINGS:
Cellular Use: (2 reviews)

In Model Organisms: (2 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
    • IC50:2 nM
    • Dmax:100 %
    Degrader (PROTAC)
    up to 30 nM
    up to 100 nM

    Selectivity

    In Cell Selectivity Assessment
    Potency Assay Off-Target:
    MD-265 was evaluated in a panel of acute leukemia cell lines. In each of these acute leukemia cell l ...

    Potency
    Cellular
    In Vitro

    MDM2

    Mode of Action: Degrader (PROTAC)

    Structure-Activity-Relationship data available? No

    DOI Reference: 10.1021/acs.jmedchem.4c01818

    In Vivo Validations

    Mouse
    Dose: 10 mf/Kg
    Route of delivery: Intravenous
    Plasma half life: 6.1 h
    Systemic clearance: 1.1 mL/min/Kg
    Area Under the Curve:: 156 μg·h/mL
    Volume of Distribution at Steady-State: 0.54 L/Kg

    DOI Reference: 10.1021/acs.jmedchem.4c01818

    Rat
    Dose: 5 mg/kg
    Route of delivery: Intravenous
    Plasma half life: 5.6 h
    Systemic clearance: 3.2 mL/min/Kg
    Area Under the Curve:: 13 μg·h/mL
    Volume of Distribution at Steady-State: 0.15 L/Kg

    DOI Reference: 10.1021/acs.jmedchem.4c01818

    Dog
    Dose: 2.5 mg/Kg
    Route of delivery: Intravenous
    Plasma half life: 6.3 h
    Systemic clearance: 7.4 mL/min/Kg
    Area Under the Curve:: 5.5 μg·h/mL
    Volume of Distribution at Steady-State: 0.93 L/Kg

    DOI Reference: 10.1021/acs.jmedchem.4c01818

    Negative Control Compounds

    canSAR7437537
    Notes: In 30a, the MDM2 inhibitor portion in MD-265 was replaced with its enantiomer.
    canSAR7437563
    Notes: In 30b, a N-methyl group was inserted onto the piperidine-2,6-dione moiety of the cereblon ligand to block its binding to cereblon.

    Chemical Information

    Molecular Formula C50H51Cl2FN6O6
    SMILEs O=C1CCC(N2Cc3c(C#CC4CCN(C(=O)[C@H]5CC[C@H](NC(=O)[C@@H]6NC7(CCCCC7)[C@@]7(C(=O)Nc8cc(Cl)ccc87)[C@H]6c6cccc(Cl)c6F)CC5)CC4)cccc3C2=O)C(=O)N1
    InChI InChI=1S/C50H51Cl2FN6O6/c51-31-14-17-36-38(26-31)55-48(65)50(36)41(34-8-5-9-37(52)42(34)53)43(57-49(50)22-2-1-3-23-49)45(62)54-32-15-12-30(13-16-32)46(63)58-24-20-28(21-25-58)10-11-29-6-4-7-33-35(29)27-59(47(33)64)39-18-19-40(60)56-44(39)61/h4-9,14,17,26,28,30,32,39,41,43,57H,1-3,12-13,15-16,18-25,27H2,(H,54,62)(H,55,65)(H,56,60,61)/t30-,32-,39?,41-,43+,50+/m0/s1
    Molecular weight 920.32 Da
    AlogP 6.507200000000005
    HBond acceptors 12
    HBond donors 4
    Atoms 116

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    Expert Reviews

    by SERP
    (on 28 Nov 2024 )
    Cellular Use Rating
    In Model Organisms
    This probe is a very promising probe for MDM2 degradation with appropriate negative controls and would highly recommend using MD-265 between 10-50 nM for cellular in vitro assays and use in vivo via the...
    by SERP
    (on 3 Dec 2024 )
    Cellular Use Rating
    In Model Organisms
    This is a high quality chemical probe for investigating MDM2 function in cells and in vivo. One point of caution is a lack of proteome wide specificity evaluation and so off-targets and their contribution...
    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