Biological Activity
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]. Cell Proliferation Assay[1] Cell Line: TMD8 and SU-DHL8 cells Concentration: 1, 3, 5 μM Incubation Time: For 24 hours Result: Resulted in decreased proliferation of viable ABC and GCB DLBCL cells. Cell Viability Assay[1] Cell Line: SU-DHL8 and TMD8 cells Concentration: 3 μM Incubation Time: For 24 hours Result: Decreased cell viability in a dose-dependent fashion. Western Blot Analysis[2] Cell Line: Primary chronic lymphocytic leukemia (CLL) cells and cell lines Concentration: 1, 5, 10 μM Incubation Time: For 6 hours Result: Documented Diminished expression of p65 and p50 in nuclear and cytosolic fractions and also decreased the expression of the inhibitory subunit IκBα both in the phosphorylated and non-phosphorylated forms.
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 T1/2 and Cmax[1]. Animal Model: BALB/C-Tg (NFkB-RE-luc)-Xen mice with 6-9 weeks old[1] Dosage: 24 mg/kg Administration: IP; every other day for 2 weeks Result: Had an effective treatment of acute GVHD without impairing anti-tumor activity.
References & source
Published experimental findings depend on the model and assay conditions. They do not guarantee equivalent performance in every application. For laboratory research use only.
