CX-5461 dihydrochloride
Based on 71 publication(s) in Google Scholar
CX-5461 dihydrochloride 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).
Nur für Forschungszwecke. Wir verkaufen nicht an Patienten.
- Reinheit: 99.41%
- Formel: C27H29Cl2N7O2S
- Molecular Weight:586.54
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Speicherung:
4°C, sealed storage, away from moisture
* In solvent : -80°C, 2 years; -20°C, 1 year (sealed storage, away from moisture)
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Publications Citing Use of MedChemExpress (MCE) CX-5461 dihydrochloride
More- Nature. 2025 Aug;644(8076):557-566. [Abstract]
- Science. 2026 Feb 26;391(6788):eadz3121. [Abstract]
- Cell. 2024 Mar 28;187(7):1701-1718.e28. [Abstract]
- Mol Cancer. 2024 Dec 20;23(1):275. [Abstract]
- Nat Cell Biol. 2022 Jul;24(7):1154-1164. [Abstract]
- Cancer Res. 2022 Mar 15;82(6):1013-1024. [Abstract]
- J Extracell Vesicles. 2023 Oct;12(10):e12361. [Abstract]
- Nat Commun. 2026 Feb 2;17(1):2252. [Abstract]
- Nat Commun. 2025 Jul 14;16(1):6489. [Abstract]
- Nat Commun. 2025 Jan 4;16(1):390. [Abstract]
- Nat Commun. 2025 Jan 2;16(1):121. [Abstract]
- Nat Commun. 2024 Feb 9;15(1):1231. [Abstract]
- Nat Commun. 2022 Jun 28;13(1):3706. [Abstract]
- Nat Commun. 2017 Sep 25;8(1):693. [Abstract]
- Mol Cell. 2025 Sep 18;85(18):3425-3442.e10. [Abstract]
- Nucleic Acids Res. 2022 May 6;50(8):4574-4600. [Abstract]
- Sci Adv. 2023 Sep;9(35):eadg7125. [Abstract]
- Mol Biomed. 2026 Apr 17;7(1):53. [Abstract]
- Blood Cancer Discov. 2026 Jul 1;7(4):624-641. [Abstract]
- Cell Death Dis. 2025 Nov 7;16(1):812. [Abstract]
- Cell Death Dis. 2024 Mar 29;15(3):236. [Abstract]
- Cell Commun Signal. 2022 Sep 5;20(1):96. [Abstract]
- Clin Cancer Res. 2017 Nov 1;23(21):6529-6540. [Abstract]
- Acta Biomater. 2018 Oct 1:79:317-330. [Abstract]
- J Transl Med. 2024 Dec 25;22(1):1147. [Abstract]
- Dev Cell. 2026 Mar 12:S1534-5807(26)00079-1. [Abstract]
- Int J Biol Macromol. 2025 Sep;322(Pt 1):146723. [Abstract]
- Int J Biol Macromol. 2025 May 15:144179. [Abstract]
- Mol Ther Oncol. 2024 Feb 7;32(1):200771. [Abstract]
- Free Radic Biol Med. 2024 Aug 5:S0891-5849(24)00589-6. [Abstract]
- EMBO Mol Med. 2021 Mar 5;13(3):e12834. [Abstract]
- Cell Prolif. 2025 May 4:e70052. [Abstract]
- Anal Chem. 2025 Jun 10;97(22):11617-11626. [Abstract]
- Mol Cancer Ther. 2018 Jun;17(6):1177-1186. [Abstract]
- Eur J Med Chem Rep. 2025 Dec.
- Life Sci. 2026 Jun 9:401:124530. [Abstract]
- J Cell Biol. 2023 Jan 2;222(1):e202202110. [Abstract]
- Matrix Biol. 2024 Dec:134:93-106. [Abstract]
- Eur J Pharmacol. 2025 Sep 15:1003:177942. [Abstract]
- Molecules. 2019 Dec 4;24(24):4445. [Abstract]
- Am J Pathol. 2021 Jun;191(6):1094-1107. [Abstract]
- Cell Signal. 2025 Nov:135:111998. [Abstract]
- FASEB J. 2020 Jun;34(6):8283-8295. [Abstract]
- Biochim Biophys Acta. 2017 Dec 8;1862(3):615-629. [Abstract]
- Development. 2024 Nov 1;151(21):dev202875. [Abstract]
- Exp Cell Res. 2025 Jun 2;450(2):114629. [Abstract]
- Biochimie. 2022 Apr 20;199:81-91. [Abstract]
- Invest New Drugs. 2021 Oct;39(5):1213-1221. [Abstract]
- Tissue Cell. 2025 Aug 18:97:103093. [Abstract]
- Open Biol. 2025 Feb;15(2):240183. [Abstract]
- Life Sci Alliance. 2019 Feb 26;2(2):e201800222. [Abstract]
- G3 (Bethesda). 2026 Mar 4;16(3):jkag008. [Abstract]
- bioRxiv. 2026 Apr 4.
- Res Sq. 2026 Apr 2.
- bioRxiv. 2026 Mar 18.
- Autophagy Rep. 2026 Feb 13;5(1):2624259. [Abstract]
- bioRxiv. 2026 Jan 7.
- bioRxiv. 2025 Nov 20:2025.11.19.689351. [Abstract]
- bioRxiv. 2025 Aug 19.
- bioRxiv. 2025 Jul 23.
- bioRxiv. 2025 May 10.
- bioRxiv. 2025 January 21.
- bioRxiv. 2024 Oct 13:2024.10.12.614958. [Abstract]
- bioRxiv. 2024 November 28.
- bioRxiv. 2024 Sep 29:2024.09.28.615444. [Abstract]
- bioRxiv. 2023 Jan 31.
- Utrecht University. 2023 Feb.
- bioRxiv. 2021 Dec.
- Biomed Pharmacother. 2021 Jan;133:110906. [Abstract]
- Patent. US20190169215A1
- Oncotarget. 2017 Oct 29;8(57):96536-96552. [Abstract]
Customer Validation & Images
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Alle DNA/RNA Synthesis Isoform-spezifische Produkte anzeigen
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Biologische Aktivität
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].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Chemical Information
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Appearance Solid
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Molecular Weight 586.54
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Formel C27H29Cl2N7O2S
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Color Light yellow to yellow
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SMILES
[H]Cl.CC1=NC=C(CNC(C2=C3N(C4=NC(N5CCN(CCC5)C)=CC=C4C2=O)C6=C(S3)C=CC=C6)=O)N=C1.[H]Cl
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Versand
Room temperature in continental US; may vary elsewhere.
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Speicherung
4°C, sealed storage, away from moisture
* In solvent : -80°C, 2 years; -20°C, 1 year (sealed storage, away from moisture)
Publications (71)
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Journal Impact Factor
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Most Recent
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Nature
2025 Aug;644(8076):557-566. PMID: 40604277 -
Science
Different repair pathways support intact or truncated insertions by R2 retrotransposon protein. [Abstract]2026 Feb 26;391(6788):eadz3121. PMID: 41231928 -
Cell
2024 Mar 28;187(7):1701-1718.e28. PMID: 38503283 -
Mol Cancer
AI-based classification of anticancer drugs reveals nucleolar condensation as a predictor of immunogenicity. [Abstract]2024 Dec 20;23(1):275. PMID: 39702289 -
Nat Cell Biol
Stalled replication fork protection limits cGAS-STING and P-body-dependent innate immune signalling. [Abstract]2022 Jul;24(7):1154-1164. PMID: 35817959 -
Cancer Res
Combined Inactivation of CTPS1 and ATR Is Synthetically Lethal to MYC-Overexpressing Cancer Cells. [Abstract]2022 Mar 15;82(6):1013-1024. PMID: 35022212 -
J Extracell Vesicles
Plant exosomes fused with engineered mesenchymal stem cell-derived nanovesicles for synergistic therapy of autoimmune skin disorders. [Abstract]2023 Oct;12(10):e12361. PMID: 37859568 -
Nat Commun
2026 Feb 2;17(1):2252. PMID: 41629347 -
Nat Commun
2025 Jul 14;16(1):6489. PMID: 40659667 -
Nat Commun
2025 Jan 4;16(1):390. PMID: 39755675 -
Nat Commun
G-quadruplex stabilization provokes DNA breaks in human PKD1, revealing a second hit mechanism for ADPKD. [Abstract]2025 Jan 2;16(1):121. PMID: 39747084 -
Nat Commun
Androgen deprivation induces double-null prostate cancer via aberrant nuclear export and ribosomal biogenesis through HGF and Wnt activation. [Abstract]2024 Feb 9;15(1):1231. PMID: 38336745 -
Nat Commun
Glutamine deficiency in solid tumor cells confers resistance to ribosomal RNA synthesis inhibitors. [Abstract]2022 Jun 28;13(1):3706. PMID: 35764642 -
Nat Commun
A role for Tau protein in maintaining ribosomal DNA stability and cytidine deaminase-deficient cell survival. [Abstract]2017 Sep 25;8(1):693. PMID: 28947735 -
Mol Cell
2025 Sep 18;85(18):3425-3442.e10. PMID: 40914169 -
Nucleic Acids Res
Guanine quadruplexes in the RNA genome of the tick-borne encephalitis virus: their role as a new antiviral target and in virus biology. [Abstract]2022 May 6;50(8):4574-4600. PMID: 35420134 -
Sci Adv
TERT accelerates BRAF mutant-induced thyroid cancer dedifferentiation and progression by regulating ribosome biogenesis. [Abstract]2023 Sep;9(35):eadg7125. PMID: 37647391 -
Mol Biomed
Lactate-driven pyrimidine synthesis promotes ferroptosis resistance in hepatocellular carcinoma. [Abstract]2026 Apr 17;7(1):53. PMID: 41996004 -
Blood Cancer Discov
2026 Jul 1;7(4):624-641. PMID: 42149820 -
Cell Death Dis
Pre-rRNAs control mitosis by maintaining chromosomal segregation through protecting SMC2 from AURKA-mediated phosphorylation. [Abstract]2025 Nov 7;16(1):812. PMID: 41203590 -
Cell Death Dis
LncRNA SNHG26 promotes gastric cancer progression and metastasis by inducing c-Myc protein translation and an energy metabolism positive feedback loop. [Abstract]2024 Mar 29;15(3):236. PMID: 38553452 -
Cell Commun Signal
Elevation of effective p53 expression sensitizes wild-type p53 breast cancer cells to CDK7 inhibitor THZ1. [Abstract]2022 Sep 5;20(1):96. PMID: 36058938 -
Clin Cancer Res
Targeting RNA-Polymerase I in Both Chemosensitive and Chemoresistant Populations in Epithelial Ovarian Cancer. [Abstract]2017 Nov 1;23(21):6529-6540. PMID: 28778862
CX-5461 dihydrochloride purchased from MedChemExpress. Usage Cited in: Clin Cancer Res. 2017 Nov 1;23(21):6529-6540. [Abstract]
Western blot analysis verifying G2/M phase arrest in 6 cell lines. Treatment with IC50 dosages of CX-5461 shows an increase in expression of pCDC2(tyr15) and Cyclin-B versus untreated controls at 72 hours.
CX-5461 dihydrochloride purchased from MedChemExpress. Usage Cited in: Clin Cancer Res. 2017 Nov 1;23(21):6529-6540. [Abstract]
Western blot analysis shows activation of the pCHK1(ser317) and pCHK2(T68), downstream substrates of ATM and ATR kinases. TP53 wild type cell lines show a subsequent activation of p21 but drug response is independent of TP53 status.
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Acta Biomater
CX-5461-loaded nucleolus-targeting nanoplatform for cancer therapy through induction of pro-death autophagy. [Abstract]2018 Oct 1:79:317-330. PMID: 30172068 -
J Transl Med
2024 Dec 25;22(1):1147. PMID: 39722009 -
Dev Cell
2026 Mar 12:S1534-5807(26)00079-1. PMID: 41825439 -
Int J Biol Macromol
TBC1D14 inhibits ribosome biogenesis to reduce lymph node metastasis in head and neck squamous cell carcinoma by mediating DDX31 ubiquitination. [Abstract]2025 Sep;322(Pt 1):146723. PMID: 40784392 -
Int J Biol Macromol
Trained immunity driven by Enterococcus faecalis ribosomal protein S11 enhances antigen presentation and boosts influenza vaccine efficacy via nanoparticle delivery. [Abstract]2025 May 15:144179. PMID: 40381785 -
Mol Ther Oncol
2024 Feb 7;32(1):200771. PMID: 38596309 -
Free Radic Biol Med
CX-5461 ameliorates disease in lupus-prone mice by triggering B-cell ferroptosis via p53-SLC7A11-ALOX12 pathway. [Abstract]2024 Aug 5:S0891-5849(24)00589-6. PMID: 39111584 -
EMBO Mol Med
NF45/NF90-mediated rDNA transcription provides a novel target for immunosuppressant development. [Abstract]2021 Mar 5;13(3):e12834. PMID: 33555115 -
Cell Prolif
Hypertranscription of rDNA Responsible for Nucleolar Remodelling is a Doorman for Acquiring Pluripotency. [Abstract]2025 May 4:e70052. PMID: 40320363 -
Anal Chem
2025 Jun 10;97(22):11617-11626. PMID: 40408126 -
Mol Cancer Ther
APTO-253 Stabilizes G-quadruplex DNA, Inhibits MYC Expression, and Induces DNA Damage in Acute Myeloid Leukemia Cells. [Abstract]2018 Jun;17(6):1177-1186. PMID: 29626127 -
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Life Sci
CAD drives Angiotensin II-induced vascular smooth muscle cell activation via upregulation of pyrimidine biosynthesis and rRNA synthesis. [Abstract]2026 Jun 9:401:124530. PMID: 42264140 -
J Cell Biol
2023 Jan 2;222(1):e202202110. PMID: 36282216 -
Matrix Biol
Loss of MMP9 disturbs cranial suture fusion via suppressing cell proliferation, chondrogenesis and osteogenesis in mice. [Abstract]2024 Dec:134:93-106. PMID: 39374863 -
Eur J Pharmacol
VOPP1, a determinant of the sensitivity of non-small cell lung cancer cells to NAE inhibitors. [Abstract]2025 Sep 15:1003:177942. PMID: 40651787 -
Molecules
CX-5461 Inhibits Pancreatic Ductal Adenocarcinoma Cell Growth, Migration and Induces DNA Damage. [Abstract]2019 Dec 4;24(24):4445. PMID: 31817270 -
Am J Pathol
MYC-Mediated Ribosomal Gene Expression Sensitizes Enzalutamide-resistant Prostate Cancer Cells to EP300/CREBBP Inhibitors. [Abstract]2021 Jun;191(6):1094-1107. PMID: 33705753 -
Cell Signal
CX-5461 inhibits cell proliferation and induces ferroptosis of colorectal cancer cells by inactivating Nrf2 pathway. [Abstract]2025 Nov:135:111998. PMID: 40664345 -
FASEB J
Transient inhibition of rDNA transcription in donor cells improves ribosome biogenesis and preimplantation development of embryos derived from somatic cell nuclear transfer. [Abstract]2020 Jun;34(6):8283-8295. PMID: 32323360 -
Biochim Biophys Acta
c-MYC G-quadruplex binding by the RNA polymerase I inhibitor BMH-21 and analogues revealed by a combined NMR and biochemical Approach. [Abstract]2017 Dec 8;1862(3):615-629. PMID: 29229300 -
Development
Ribosome biogenesis is essential for hemogenic endothelial cells to generate hematopoietic stem cells. [Abstract]2024 Nov 1;151(21):dev202875. PMID: 39324287 -
Exp Cell Res
Metastatic breast cancer cells adapt to a soft environment with limited involvement of mechanotransduction. [Abstract]2025 Jun 2;450(2):114629. PMID: 40466802 -
Biochimie
Probing the folding pathways of four-stranded intercalated cytosine-rich motifs at single base-pair resolution. [Abstract]2022 Apr 20;199:81-91. PMID: 35452743 -
Invest New Drugs
Discovery of MTR-106 as a highly potent G-quadruplex stabilizer for treating BRCA-deficient cancers. [Abstract]2021 Oct;39(5):1213-1221. PMID: 33710464 -
Tissue Cell
Combined inhibition of WEE1 by AZD1775 synergistically enhances CX-5461 mediated DNA damage and induces cytotoxicity in glioblastoma. [Abstract]2025 Aug 18:97:103093. PMID: 40839955 -
Open Biol
2025 Feb;15(2):240183. PMID: 39965659 -
Life Sci Alliance
FUS (fused in sarcoma) is a component of the cellular response to topoisomerase I-induced DNA breakage and transcriptional stress. [Abstract]2019 Feb 26;2(2):e201800222. PMID: 30808650 -
G3 (Bethesda)
CX-5461 and doxorubicin activate a shared DNA damage-associated transcriptional response in human cardiomyocytes. [Abstract]2026 Mar 4;16(3):jkag008. PMID: 41543508 -
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Autophagy Rep
2026 Feb 13;5(1):2624259. PMID: 41717449 -
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bioRxiv
Dual RNA Polymerase I Inhibition with CX-5461 and BMH-21 Synergizes in Breast Cancer by Activating p53-Dependent Stress. [Abstract]2025 Nov 20:2025.11.19.689351. PMID: 41332727 -
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bioRxiv
2024 Oct 13:2024.10.12.614958. PMID: 39498261 -
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bioRxiv
2024 Sep 29:2024.09.28.615444. PMID: 39386460 -
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Biomed Pharmacother
Combined inhibition of RNA polymerase I and mTORC1/2 synergize to combat oral squamous cell carcinoma. [Abstract]2021 Jan;133:110906. PMID: 33190037 -
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Oncotarget
Human cytomegalovirus and Herpes Simplex type I virus can engage RNA polymerase I for transcription of immediate early genes. [Abstract]2017 Oct 29;8(57):96536-96552. PMID: 29228551
CX-5461 dihydrochloride purchased from MedChemExpress. Usage Cited in: Oncotarget. 2017 Oct 29;8(57):96536-96552. [Abstract]
Protein levels of HCMV IE (IE1:IE72, IE2:IE86) and pp65 are detected by WB analysis in untreated and pre-treated HCMV infected cells 72hpi.
Lösungsmittel & Löslichkeit
H2O : 5 mg/mL (8.52 mM; ultrasonic and warming and heat to 80°C)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year (sealed storage, away from moisture). When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year (sealed storage, away from moisture). When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.
Konzentration (Stammlösung) × Volumen (Stammlösung) = Konzentration (Ziellösung) × Volumen (Ziellösung)
Protokoll
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].
MedChemExpress (MCE) 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 − (VfD− ViD)/ (VfV − ViV) × 100], where ViV is the initial mean tumor volume in vehicle-treated group, VfV is the final mean tumor volume in vehicle-treated group, ViD is the initial mean tumor volume in drug-treated group, and VfD is the final mean tumor volume in drug-treated group.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Reinheit & Dokumentation
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Data Sheet (281 KB)
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SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
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Handling Instructions (2659 KB)
Verweise
[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. [Content Brief]
[2]. Bywater MJ, et al. Inhibition of RNA Polymerase I as a Therapeutic Strategy to Promote Cancer-Specific Activation of p53. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year (sealed storage, away from moisture). When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| H2O | 1 mM | 1.7049 mL | 8.5246 mL | 17.0491 mL | 42.6228 mL |
| 5 mM | 0.3410 mL | 1.7049 mL | 3.4098 mL | 8.5246 mL |
* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.
CX-5461 dihydrochloride Related Classifications
HY-13323A Related Classifications
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