Minhua Su, Tom Fleisher, Inna Grosheva, Melanie Bokstad Horev, Malgorzata Olszewska, Camilla Ciolli Mattioli, Haim Barr, Alexander Plotnikov, Silvia Carvalho, Yoni Moskovich, Mark D Minden, Noa Chapal-Ilani, Alexander Wainstein, Eirini P Papapetrou, Nili Dezorella, Tao Cheng, Nathali Kaushansky, Benjamin Geiger, Liran I Shlush
Spliceosome machinery mutations are common early mutations in myeloid malignancies; however, effective targeted therapies against them are still lacking. In the current study, we used an in vitro high-throughput drug screen among four different isogenic cell lines and identified RKI-1447, a Rho-associated protein kinase inhibitor, as selective cytotoxic effector of SRSF2 mutant cells. RKI-1447 targeted SRSF2 mutated primary human samples in xenografts models. RKI-1447 induced mitotic catastrophe and induced major reorganization of the microtubule system and severe nuclear deformation...
April 19, 2024: IScience