Discovery of SD-2301 as a Highly Potent and Selective PROTAC STAT3 Degrader Capable of Achieving Complete Tumor Regression with Single Administration.
Researchers engineered a powerful molecular tool that rapidly shrinks anaplastic lymphomas in models, suggesting new therapeutic possibilities.
Researchers at the University of Michigan developed SD-2301, a novel VHL-recruiting PROTAC STAT3 degrader with DC50=4nM and maximal degradation >95%, representing more than 100-fold potency improvement over prior STAT3 PROTACs SD-36 and SD-91. In anaplastic large cell lymphoma xenograft mouse models, SD-2301 achieved rapid and durable complete tumor regression following a single dose, with favorable pharmacokinetics in mice.
What the study was
- Study design
- preclinical
- Category
- targeted protein degradation / PROTAC
- Maturity
- Exploratory
- Journal
- Journal of Medicinal Chemistry
Why it surfaced
Breakthrough potency for STAT3 degradation (100x improvement over prior generation) from Shaomeng Wang's lab at U-Michigan—leading PROTAC group worldwide. STAT3 is a validated oncogene in multiple hematologic malignancies (ALCL, DLBCL, T-cell lymphoma). Complete tumor regression with single dose is an exceptional preclinical finding. Scored STANDARD (preclinical, score 7); does not qualify for AUTO-HIGH without clinical validation.
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