Fluorizoline

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]. In Vitro: 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].
In Vivo: 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].