A novel tubulin binding molecule drives differentiation of acute myeloid leukaemia cells

Here we perform a phenotypic screen and identified novel compounds that can promote differentiation in several AML cell lines. Lead compounds are able to decrease tumour burden and increase survival in vivo. Using multiple complementary target deconvolution approaches (including chemoproteomics), these compounds were revealed to be anti-mitotic tubulin disruptors that cause differentiation by inducing a G2-M mitotic arrest. Together, these results reveal a novel function for tubulin disruptors in causing differentiation of AML cells.