In Vitro: TCIP 1 increases BRD4 binding at the BCL6 binding site of the genome by 50%, while reducing BRD4 binding at the enhancer by only 10%. This results in transcriptional elongation at the pro-apoptotic target gene, which has a significant inhibitory effect on diffuse large B-cell lymphoma cell lines, including chemotherapy-resistant TP53 mutant cell lines, EC50=1-10 nM. TCIP 1-induced apoptosis can be prevented by JQ1 (BRD4 inhibitor) or BI3812 (BCL6 inhibitor). TCIP 1 induces both a G1/S and G2/M block in KARPAS422 cells. TCIP 1 (10 or 100 nM; 20 h) significantly activates ro-apoptotic genes and (10 nM; 8 h) represses MYC and its targets expression.
In Vivo: TCIP1 (10 mg/kg; ip; once daily for 5 days) is well tolerated in wild-type C57BL/6 mice, with t1/2 of 9.7 h, Cmax of 0.41 μM, and AUC0-last of 1.92 μM/h, respectively.