Activity of PROTAC MDM2 degrader in primary leukemia cells and PDX models
A promising experimental drug selectively targets leukemia stem cells in lab and animal models while sparing healthy blood cells, advancing a novel approach to hard-to-treat AML.
The PROTAC MDM2 degrader MD-265 demonstrates potent and selective preclinical activity against AML leukemic stem cells with an IC50 of 16 nM—150-fold more potent than current MDM2 inhibitors—and 100-fold selectivity over normal hematopoietic stem cells. PDX model data show survival benefit without toxicity, establishing MD-265 as a clinical candidate for wt-TP53 AML where MDM2 overexpression limits p53 activity.
What the study was
- Study design
- Ex vivo primary human cell testing + PDX mouse model
- Population
- Primary AML leukemic stem cells (n=105 samples) and NSG-SGM3 mouse PDX models
- Sample size
- 105
- Category
- Drug Development
- Maturity
- Exploratory
- Journal
- Leukemia
Why it surfaced
PROTAC approach overcomes MDM2 inhibitor feedback limitation; 105 primary patient samples provide clinical relevance; scored conservatively for mixed human/animal design.
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