MG-277
Molecular Glue Degrader of GSPT1
Structure
In Cells
(1
ratings)
In Model Organisms
(0
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Probe MG-277 is in the process of SERP review.
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SERP ratings and comments
SERP Ratings
In Cell Rating
SERP Comments:
MG-277 is a well-characterized degrader that depletes GSPT1 levels in several breast cancer and leukemia cell lines. The characterization included quantitative proteomic experiments (done at 100nM concentration and 3h treatment), which showed that GSPT1 was the major degradation target for MG-277. Additionally, phenotypic effects were shown to depend on the presence of the target and cereblon (CRBN), and depletion of GSPT1 levels upon MG-277 was shown to depend on the proteasome activity. The authors also describe a negative control compound (MC-024), which should be used in combination with MG-277. Please note that MG-277 retains binding to MDM2 (the target it was originally developed for but failed to degrade effectively), so some care needs to be taken when used to study GSPT1, especially if dealing with cells that express high levels of MDM2 relative to GSPT1. Finally, the original report includes compound MC-217 that has lost MDM2 binding. Therefore, it would be of benefit to characterize and validate this molecule further as it may represent a preferred probe given the lack of MDM2 binding.
(last updated: 7 Jul 2021 )