IT-901

IT-901 is an orally active and potent NF-κB subunit c-Rel inhibitor with an IC₅₀ of 0.1 µM, 3 μM for NF-κB DNA binding and c-Rel DNA binding, respectively. IT-901, a bioactive naphthalenethiobarbiturate derivative, has the potential for human lymphoid tumors and ameliorate graft-versus-host disease (GVHD)^[1][2]. In Vitro: IT-901 (1, 3, 5 μM; for 24 hours) results in decreased proliferation of viable ABC and GCB DLBCL cells^[1].
IT-901 (3 μM; for 24 hours) decreases cell viability in a dose-dependent fashion, at least 60 percent of cells were still viable after 48 hours of IT-901 treatment (4μM) in all tested cell lines except HBL1^[1].
IT-901 (1, 5, 10 μM; for 6 hours) documents Diminished expression of p65 and p50 in nuclear and cytosolic fractions and also decreases the expression of the inhibitory subunit IκBα both in the phosphorylated and non-phosphorylated forms in primary CLL cells and cell lines^[2].
The IC₅₀ of IT-901/GDM-12 is 2.9 μM for c-Rel whereas IL-2 secretion is successfully blocked at 5 μM^[1].
The concentrations of IT-901 above 10 μM become increasingly toxic and may lead to apoptosis of healthy cells^[1].
IT-901 inhibits cell growth of both activated B-like (ABC) and germinal center B-like (GCB) cell lines with the IC₅₀ values between 3μM to 4μM^[1].
In Vivo: IT-901 (24 mg/kg; IP; every other day for 2 weeks) has an effective treatment of acute GVHD without impairing anti-tumor activity^[1].
IT-901 (12-20 mg/kg; IP) improves the PK profile by increasing T_1/2 and C_max^[1].