CX-5461 dihydrochloride 是一种有效的，可口服的 Pol I 介导的rRNA synthesis抑制剂，在 HCT-116，A375 和 MIA PaCa-2 细胞中，IC50值分别为 142 nM，113 nM 和 54 nM，对 Pol II 作用不大 (IC50≥25 μM)。

CX-5461 dihydrochloride is a potent and orally bioavailable inhibitor of Pol I-mediated rRNA synthesis, with IC 50 s of 142 nM in HCT-116, 113 nM in A375, and 54 nM in MIA PaCa-2 cells, and shows little or no effect on Pol II ( IC 50 ≥25 μM).

CX-5461 is a potent and orally bioavailable inhibitor of Pol I-mediated rRNA synthesis, with IC 50 s of 142 nM in HCT-116, 113 nM in A375, and 54 nM in MIA PaCa-2 cells, and shows little or no effect on Pol II (IC 50, ≥25 μM). CX-5461 has modest inhibition on DNA replication and protein translation. CX-5461 also exhibits broad antiproliferative activity against a panel of human cancer cell lines, with a mean EC 50 of 147 nM, but has minimal effect on viability of nontransformed human cells, with EC 50 values of appr 5000 nM. EC 50 s of CX-5461 for HCT-116, A375, and MIA PaCa-2 cell lines are 167, 58, and 74 nM, respectively. CX-5461 induces autophagy and senescence in solid tumor cancer cells, rather than apoptosis, through a p53-independent process [1]. Eμ-Myc lymphoma cells from tumor-bearing mice are exquisitely sensitive to CX-5461 with an IC 50 of 27.3 nM ± 8.1 nM for Pol I transcription after 1 hr and IC 50 of 5.4 nM ± 2.1 nM for cell death after 16 hr. CX-5461 activates p53 via the nucleolar stress response in Eμ-MycLymphoma Cells [2].

CX-5461 displays antitumor activity against human solid tumors in murine xenograft models. CX-5461 (50 mg/kg, p.o.) shows significant MIA PaCa-2 growth inhibition with TGI equal to 69% on day 31 and 79% TGI on A375 on day 32 [1]. CX-5461 (50 mg/kg, p.o.) inhibits the Eμ-Myc tumor cells with 84% repression in Pol I transcription at 1 hr posttreatment in C57BL/6 mice. CX-5461 also induces a rapid reduction in tumor burden in the lymph nodes and a concomitant reduction of spleen size to within the normal range [2].

C27H29Cl2N7O2S

586.54

(< 1 mg/ml refers to the product slightly soluble or insoluble )
Powder: -20°C for 3 years
In solvent: -80°C for 2 years