| Bioactivity | TCIP 1 is a transcriptional/epigenetic CIPs (TCIP) small molecule consisting of covalent links to small molecules capable of binding to BCL6 and capable of binding to BRD4, respectively. TCIPs aids cell death gene expression by recruiting endogenous cancer drivers or downstream transcription factors to the promoters of cell death genes. TCIP 1 also plays a gain-of-function mechanism with shows cell specificity and tissue specificity. TCIP 1 forms a gain-of-function ternary complex with BCL6 and BRD4, Inhibits the blocking effect of BCL6 on apoptosis gene, and generates transcriptional extension of pro-apoptotic genes, thus activates apoptosis. TCIP 1 also significantly inhibits the expression of the oncogene MYC and inhibits the growth of diffuse large B-cell lymphoma (DLBCL)[1]. |
| Invitro | TCIP 1 使 BRD4 在基因组 BCL6 结合位点上的结合增加了 50%，而使 BRD4 在增强子上的结合仅减少 10%。由此导致了促凋亡靶基因处产生转录延伸，对弥漫性大 B 细胞淋巴瘤细胞系，包括化疗耐药的 TP53 突变细胞系有显著抑制作用，EC50=1-10 nM[1]。而 TCIP 1 诱导的凋亡能够被 JQ1 (BRD4 抑制剂) 或 BI3812 (BCL6 抑制剂) 阻止。TCIP 1 在 KARPAS422 细胞中诱导 G1/S 和 G2/M 阻滞。TCIP 1 (10 或 100 nM；20 h) 显著激活反凋亡基因，(10 nM；8 h) 抑制 MYC 及其靶基因的表达。 |
| In Vivo | TCIP1 (10 mg/kg；腹腔注射；每日 1 次，连续 5 天) 在野生型 C57BL/6 小鼠中耐受良好，t1/2 为 9.7 h, Cmax 为 0.41 μM, AUC0-last 为 1.92 μM/h[1]。 |
| Name | TCIP 1 |
| Formula | C50H58Cl2N12O6S |
| Molar Mass | 1026.04 |
| Transport | Room temperature in continental US; may vary elsewhere. |
| Storage | Please store the product under the recommended conditions in the Certificate of Analysis. |
| Reference | [1]. Gourisankar S, et al. Rewiring cancer drivers to activate apoptosis. Nature. 2023 Jul 26. |