| In vitro |
CC-115 inhibits the DNA damage repair pathway and TORK in CLL cells and induces caspase-dependent cell death in resting CLL cells. It induces cell death with an IC50 of 0.51 µM. CC-115 reverts CD40-induced chemoresistance. CC-115 treatment significantly reduces induction of expression Mcl-1, Bfl-1, and Bcl-XL on CD40 stimulation in CLL cells. It also blocks proliferation of CLL cells. In healthy B cells, CC-115 induces cell death with an IC50 of 0.93 µM. CC-115 and NU7441 completely block the proliferation of CD4+ and CD8+ T cells. Taken together, CC-115 induces direct cytotoxicity and can block signaling pathways that are important for CLL survival, chemo-resistance and proliferation in the in the LN microenvironment[1].
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| In vivo |
CC-115 decreases lymphadenopathy in CLL patients[1]. CC-115 shows good in vivo PK profiles across multiple species with 53%, 76%, and ∼100% oral bioavailability in mouse, rat, and dog, respectively. CC-115 has favorable physicochemical and pharmacokinetic properties, demonstrates in vivo mTOR pathway inhibition and tumor growth inhibition, as well as a good in vitro and in vivo safety profile, suitable for clinical development[2].
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COA
HPLC