Fluorizoline selectively and directly binds to prohibitin 1 (PHB1) and 2 (PHB2), and induces apoptosis. Fluorizoline reduces chronic lymphocytic leukemia (CLL) cell viability through the upregulation of NOXA and BIM. Fluorizoline exerts antitumor action in a p53-independent manner[1].
Fluorizoline (1.25-20 μM; 24 hours) induces apoptosis in primary CLL cells ex vivo[1]. Fluorizoline (5-10 μM; 48 hours) causes an increase of NOXA protein levels[1]. Fluorizoline reduces the percentage of viable normal B and T cells (48.6% and 82.8% of viable cells at 24 hours of treatment with 10 μM Fluorizoline in normal CD19+ and CD3+ populations, respectively) with mean EC50 values of 10.9 μM and 19.1 μM at 24 hours for normal B and T cells, respectively[1].
Fluorizoline (15 mg/kg; ip; three times a week for five weeks) becomes very rapidly (3 weeks) leukemic, as reflected by the increase in the percentage and the number of CD5+CD19+ CLL cells in the blood in 6-week-old recipient C57BL/6 Eμ-TCL1 mouse model of CLL. Fluorizoline does not induce apoptosis in vivo. Fluorizoline does not control disease development in the spleen as indicated by enlarged spleens[2].
[1]. Ana M Cosialls, et al. The prohibitin-binding compound fluorizoline induces apoptosis in chronic lymphocytic leukemia cells through the upregulation of NOXA and synergizes with ibrutinib, 5-aminoimidazole-4-carboxamide riboside or venetoclax. Haematologica. 2017 Sep;102(9):1587-1593.
[2]. Marina Wierz, et al. The prohibitin-binding compound fluorizoline induces apoptosis in chronic lymphocytic leukemia cells ex vivo but fails to prevent leukemia development in a murine model. Haematologica. 2018 Apr;103(4):e154-e157.