CX-5461 (Pidnarulex)

製品コードS2684 バッチS268405

印刷

化学情報

Chemical Structure Synonyms N/A Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C27H27N7O2S
分子量 513.61 CAS No. 1138549-36-6
Solubility (25°C)* 体外 DMSO Insoluble
Water Insoluble
Ethanol Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 Pidnarulex (CX-5461) is an inhibitor of rRNA synthesis, selectively inhibits Pol I-driven transcription of rRNA with IC50 of 142 nM in HCT-116, A375, and MIA PaCa-2 cells, has no effect on Pol II, and possesses 250- to 300-fold selectivity for inhibition of rRNA transcription versus DNA replication and protein translation.
in vitro

CX-5461 (Pidnarulex) is found to selectively inhibit rRNA synthesis (Pol I IC50=142 nM; Pol II IC50 > 25 μM; selectivity ~200-fold) in the HCT-116 cells. Selective inhibition of rRNA synthesis by this compound is confirmed in two other human solid tumor cell lines; melanoma A375 (Pol I IC50 = 113 nM; Pol II IC50 > 25 μM) and pancreatic carcinoma MIA PaCa-2 (Pol I IC50=54 nM; Pol II IC50 ~25 mM). It possesses 250- to 300-fold selectivity for inhibition of rRNA transcription versus DNA replication and protein translation. This compound exhibits broad antiproliferative potency in a panel of cancer cell lines in human cancer cell lines, but has minimal effect on viability of nontransformed human cells. The median EC50 across all tested cell lines is 147 nM, yet all normal cell lines have EC50 values of approximately 5, 000 nM. Evaluation of the antiproliferative dose response for HCT-116, A375, and MIA PaCa-2 cell lines yield EC50 values of 167, 58, and 74 nM. It induces autophagy and senescence in solid tumor cancer cells, rather than apoptosis, through a p53-independent process. [1]
in vivo

CX-5461 (Pidnarulex) is orally bioavailable and demonstrates in vivo antitumor activity against human solid tumors in murine xenograft models. It demonstrates significant MIA PaCa-2 TGI with TGI equal to 69% on day 31. Likewise, this compound demonstrates significant A375 TGI with TGI equal to 79% on day 32. [1]

プロトコル(参考用のみ)

キナーゼアッセイ Pol I and Pol II Transcription Assay
Two short-lived RNA transcripts (half-lives ~20-30 minutes), one produced by Pol I and another by Pol II, are quantitated by qRT-PCR as a measure of CX-5461 (Pidnarulex)-related effects on transcription. The 45S pre-rRNA served as the Pol I transcript and the mRNA for the protooncogene c-myc served as the comparator Pol II transcript. Both Pol I and Pol II transcription are known to be affected by general cellular stress. To minimize the potential effects of such stress, cells are exposed to test agents for only a short period of time (2 hours). This is sufficient time for these transcripts to be reduced by greater than 90% if it affects their synthesis.
細胞アッセイ 細胞株 panel of cancer and normal cell lines
濃度 0-2 μM
反応時間 96 hours
実験の流れ

Following plating on 96-well plates, cells are treated the next day with a dose response of CX-5461 (Pidnarulex) for 96 hours. Cell viability is determined using Alamar Blue and CyQUANT assays.
動物実験 動物モデル 5 × 106 MIA Paca-2 and A375 cancer cells are subcutaneously inoculated in the right flank of 5- to 6- week-old female athymic mice
投薬量 50 mg/kg
投与方法 CX-5461 is administered orally once daily or every 3 days.

参考

  • https://pubmed.ncbi.nlm.nih.gov/21159662/

カスタマーフィードバック

Data from [Data independently produced by PLoS One, 2014, 9(8), e104364]

Data from [Data independently produced by , , Cell, 2018, 174(2):338-349]

Data from [Data independently produced by , , Oncogene, 2015, 10.1038/onc.2015.147]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Guanine nucleotide biosynthesis blockade impairs MLL complex formation and sensitizes leukemias to menin inhibition [ Nat Commun, 2025, 16(1):2641] PubMed: 40102405
Genetic regulation of TERT splicing affects cancer risk by altering cellular longevity and replicative potential [ Nat Commun, 2025, 16(1):1676] PubMed: 39956830
ATRX cooperates with TOP2B for replication fork stability and DNA damage response through G-quadruplex regulation [ Nucleic Acids Res, 2025, 53(18)gkaf939] PubMed: 40990248
Downregulation of rRNA synthesis by BCL-2 induces chemoresistance in diffuse large B cell lymphoma [ iScience, 2025, 28(5):112333] PubMed: 40276769
Actionable heterogeneity of hepatocellular carcinoma therapy-induced senescence [ Cancer Immunol Immunother, 2025, 74(7):207] PubMed: 40374812
Establishment of an imaging-based screening pipeline for the identification of human ribosome biogenesis inhibitors [ BMC Biol, 2025, 23(1):315] PubMed: 41121194
Optimizing GBM organoid construction with hydrogel-based models: GelMA-HAMA scaffold supports GBM organoids with clonal growth for drug screening [ Cell Transplant, 2025, 34:9636897251347537] PubMed: 40556129
Calcium signals shape metabolic control of H3K27ac and H3K18la to regulate EGA [ bioRxiv, 2025, 2025.03.14.643362] PubMed: 40161793
Role of the NuRD complex and altered proteostasis in cancer cell quiescence [ bioRxiv, 2025, 2025.02.10.637435] PubMed: 39990343
Silvestrol inhibits nasopharyngeal carcinoma cells and synergizes with CX-5461: Insights from a proteomics study [ Mol Clin Oncol, 2025, 23(5):95] PubMed: 40901568

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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