Machine learning-guided discovery of withangulatin A as a novel inducer of megakaryocytic differentiation through direct targeting of TYK2 in leukemia.
A natural compound from plants shows promise as a leukemia therapy by triggering cancer cells to mature and stop growing.
Machine learning screening of 113 withanolides from Physalis angulata identified withangulatin A as a potent inducer of megakaryocytic differentiation in non-APL leukemia through direct TYK2 targeting, validated by SPR, CETSA, and DARTS target engagement assays. In vivo studies in a syngeneic mouse model and primary human AML samples confirmed differentiation-inducing activity and prolonged survival, establishing WA as a promising natural product lead for differentiation therapy in non-APL leukemia.
What the study was
- Study design
- Preclinical (in vitro + in vivo animal model + primary human cells)
- Population
- K562 and HEL leukemia cell lines; syngeneic leukemia mouse model; primary human non-APL AML samples
- Category
- Drug Development
- Maturity
- Exploratory
- Journal
- Phytomedicine
Why it surfaced
Novel TYK2-targeting natural product discovered by ML-guided screening; validated in primary human cells; addresses differentiation therapy gap in non-APL leukemia where targeted differentiating agents are lacking.
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