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MD-224 | 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
  • Ki:0.16 nM
  • IC50:4.4 nM
  • IC50:1.5 nM
Degrader (PROTAC)
In certain cell lines (e.g, MV411), concentrations > 30 nM may be needed to achieve complete degradation of MDM2 after treatment for 2h.
up to 30 nM

Selectivity

In Cell Selectivity Assessment
Potency Assay Off-Target:
Cell Growth Inhibition Activity
Selectivity Assessment Description:
Cell Growth Inhibition Activity of MD-224 in a Panel of Human AML or ALL Cell Lines MOLM-13 7.3 nM, ...

Potency
Cellular
In Vitro

MDM2

Mode of Action: Degrader (PROTAC)

Structure-Activity-Relationship data available? No

DOI Reference: 10.1021/acs.jmedchem.8b00909

In Vivo Validations

Mouse
Dose: 25 mg/Kg IV once weekly, 10 mg/Kg 3 times weekly, 25 mg/Kg 5 days a week for 2 weeks, 50 mg/Kg every other day for 3 weeks
Route of delivery: Intravenous

DOI Reference: 10.1021/acs.jmedchem.8b00909

Orthogonal Probes def

MG-277

Chemical Information

Molecular Formula C48H43Cl2FN6O6
SMILEs O=C1CCC(N2Cc3c(C#CCCCNC(=O)c4ccc(NC(=O)[C@@H]5NC6(CCCCC6)[C@@]6(C(=O)Nc7cc(Cl)ccc76)[C@H]5c5cccc(Cl)c5F)cc4)cccc3C2=O)C(=O)N1
InChI InChI=1S/C48H43Cl2FN6O6/c49-29-16-19-34-36(25-29)54-46(63)48(34)39(32-12-8-13-35(50)40(32)51)41(56-47(48)22-4-2-5-23-47)44(61)53-30-17-14-28(15-18-30)42(59)52-24-6-1-3-9-27-10-7-11-31-33(27)26-57(45(31)62)37-20-21-38(58)55-43(37)60/h7-8,10-19,25,37,39,41,56H,1-2,4-6,20-24,26H2,(H,52,59)(H,53,61)(H,54,63)(H,55,58,60)/t37?,39-,41+,48+/m0/s1
Molecular weight 888.26 Da
AlogP 0.0
HBond acceptors 12
HBond donors 5
Atoms 106

References

Publications

Cross References

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Expert Reviews

by SERP
(on 9 Feb 2021 )
Cellular Use Rating
In Model Organisms
For degrader molecules, selectivity is often assessed through proteomic studies that explore the relative stability of the presumed target (here MDM2) compared to other possible targets. Although that...
by SERP
(on 18 Feb 2021 )
Cellular Use Rating
In Model Organisms
MG-277 has also been described as an optimized MDM2 degrader modified from MD-222. Ref: https://doi.org/10.1016/j.apsb.2020.01.003
by SERP
(on 21 Mar 2022 )
Cellular Use Rating
In Model Organisms
MD-224 displays potent and rapid degradation of MDM2 in cells at low nanomolar concentrations. There is indirect evidence of binding to CRBN through lenalidomide competitive binding assays. Two compounds...
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