CX-5461 is a potent and oral rRNA synthesis inhibitor. It inhibits RNA polymerase I-driven transcription of rRNA with IC₅₀s of 142, 113, and 54 nM in HCT-116, A375, and MIA PaCa-2 cells, respectively^[1].

IC50: 54 nM (rRNA synthesis, MIA PaCa-2 cells), 113 nM (rRNA synthesis, A375 cells), 142 nM (rRNA synthesis, HCT-116 cells)^[1]

CX-5461 is a potent and orally bioavailable inhibitor of Pol I-mediated rRNA synthesis, with IC₅₀s 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 (IC₅₀, ≥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 EC₅₀ of 147 nM, but has minimal effect on viability of nontransformed human cells, with EC₅₀ values of appr 5000 nM. EC₅₀s 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 IC₅₀ of 27.3 nM ± 8.1 nM for Pol I transcription after 1 hr and IC₅₀ 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].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

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].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

513.61

C₂₇H₂₇N₇O₂S

1138549-36-6

Room temperature in continental US; may vary elsewhere.

DMSO : 2 mg/mL (3.89 mM; Need ultrasonic)

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。

• [1]. Drygin D et al. Targeting RNA polymerase I with an oral small molecule CX-5461 inhibits ribosomal RNA synthesis and solid tumor growth. Cancer Res. 2011 Feb 15;71(4):1418-30.

  [2]. Bywater MJ, et al. Inhibition of RNA Polymerase I as a Therapeutic Strategy to Promote Cancer-Specific Activation of p53. Cancer Cell. 2012 Jul 10;22(1):51-65.

Cells are plated on 96-well plates and treated the next day with dose response of CX-5461 for 96 hours. Cell viability is determined using Alamar Blue and CyQUANT assays^[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Mice^[1]
Animal experiments are performed with 5- to 6-week-old female athymic (NCr nu/nu fisol) mice of Balb/c. Mice are inoculated with athymic (NCr nu/nu fisol) mice in 100 μL of cell suspension subcutaneously in the right flank. Tumor measurements are performed by caliper analysis, and tumor volume is calculated using the formula (l×w²)/2, where w=width and l=length in mm of the tumor. established tumors (appr 110-120 mm³) are randomized into vehicle (50 mM NaH₂PO₄, pH 4.5), NSC 613327, or CX-5461 treatment groups. Tumor growth inhibition (TGI) is determined on the last day of study according to the formula: TGI (%)=[100 − (Vf^D− Vi^D)/ (Vf^V − Vi^V) × 100], where Vi^V is the initial mean tumor volume in vehicle-treated group, Vf^V is the final mean tumor volume in vehicle-treated group, Vi^D is the initial mean tumor volume in drug-treated group, and Vf^D is the final mean tumor volume in drug-treated group.

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

• [1]. Drygin D et al. Targeting RNA polymerase I with an oral small molecule CX-5461 inhibits ribosomal RNA synthesis and solid tumor growth. Cancer Res. 2011 Feb 15;71(4):1418-30.

  [2]. Bywater MJ, et al. Inhibition of RNA Polymerase I as a Therapeutic Strategy to Promote Cancer-Specific Activation of p53. Cancer Cell. 2012 Jul 10;22(1):51-65.