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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

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 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 comments )
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