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MI-77301 | Antagonist of MDM2
RATINGS:
Cellular Use: (4 reviews)

In Model Organisms: (4 reviews)
Probe Summary
Selectivity
Potency
In Vivo
Control Compounds
Chemical Information
References
Vendors
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Probe Summary

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Targets Biochemical/Biophysical Potency Cellular Potency
MDM2
  • Ki:0.88 nM
  • IC50:0.092 uM
Antagonist
1-10 uM

Selectivity

In Vitro Selectivity Assessment
Potency Assay Off-Target:
At 10 uM, MI-77301 did not bind MDMx as assessed by biolayer interferometry.
Selectivity Assessment Description:
At 10 uM, MI-77301 showed minimal interaction with BCL2, BCLXL, MCL1, beta-catenin and minimal ac ...

Potency
Cellular
In Vitro

MDM2

Mode of Action: Antagonist

Structure-Activity-Relationship data available? No

DOI Reference: 10.1158/0008-5472.CAN-14-0799

In Vivo Validations

Mouse
Dose: 25-200 mg/kg
Route of delivery: Oral
Organ of interest (O): SJSA-1 xenografts
Target engagement assay: In xenografts, MI-77301 dose-dependently increased p21 and PUMA RNA and increased p21, MDM2 and p53 protein expression. Comparable effects on p53 protein expression were obtained in multiple types of xenografts.

DOI Reference: 10.1158/0008-5472.CAN-14-0799

Orthogonal Probes def

RO5353
AM-6761
AMG232

Chemical Information

Molecular Formula C29H34Cl2FN3O3
SMILEs CC(C)(C)C[C@@H]1N[C@@H](C(=O)N[C@H]2CC[C@H](O)CC2)[C@H](c2cccc(Cl)c2F)[C@]12C(=O)Nc1cc(Cl)ccc12
InChI InChI=1S/C29H34Cl2FN3O3/c1-28(2,3)14-22-29(19-12-7-15(30)13-21(19)34-27(29)38)23(18-5-4-6-20(31)24(18)32)25(35-22)26(37)33-16-8-10-17(36)11-9-16/h4-7,12-13,16-17,22-23,25,35-36H,8-11,14H2,1-3H3,(H,33,37)(H,34,38)/t16-,17-,22-,23-,25+,29+/m0/s1
Molecular weight 561.20 Da
AlogP 5.3025
HBond acceptors 6
HBond donors 4
Atoms 72

Vendors

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Expert Reviews

by SERP
(on 8 Aug 2017)
Cellular Use Rating
In Model Organisms
MI-77301 (synonym SAR405838) is a highly potent and selective MDM2 inhibitor (Ki=0.88 nM). MI-77301 inhibits the cell growth of cancer cell lines like p53 wild-type osteosarcoma SJSA-1 cell line (IC50=92...
by SERP
(on 18 Aug 2017)
Cellular Use Rating
In Model Organisms
(The reviewer did not leave any public comments)
by SERP
(on 18 Aug 2017)
Cellular Use Rating
In Model Organisms
This probe is the result of extensive chemistry optimization over the last 10 years. The original compound was a rationally designed inhibitor of the interaction between p53 and MDM2, but it had liabilities...
by SERP
(on 29 Apr 2019)
Cellular Use Rating
In Model Organisms
(The reviewer did not leave any public comments)
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