AB8939 is a new small-molecule drug that binds to tubulin and induces a rapid destabilisation of microtubules. Through disorganisation of microtubules, AB8939 is able to induce the apoptosis at nanomolar concentration of a wide panel of tumor cell lines, in particular hematopoietic tumor cell lines (i.e. cancers that affect the blood and lymph system) and in patient blasts.
AB8939 shows a strong dose-dependent anti-leukemia activity and efficacy in resistant-doxorubicin and cytarabine models overcoming multidrug resistance.
Anti-proliferative activity of AB8939 compared to doxorubicin
In particular, AB8939 is efficient in killing doxorubicin-resistant cell line (MES-SA/Dx5) that overexpress glycoprotein (Pgp/MDR1).
Furthermore, AB8939 increases the survival of animals in acute myeloid leukemia model. AB8939 displays an anti-leukemic activity in this AML mouse model (AMKL26 model), as evidenced by the eradication of the blasts in the bone marrow in mice treated with AB8939.
Bone marrow blasts eradication in acute megakaryoblastic leukemia patient-derived xenograft mouse model
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