CX-5461
RNA polymerase I inhibitor / CX-5461 (1138549-36-6) is a first-in-class selective RNA polymerase I inhibitor, suppressing Pol I transcription in MV 4;11 myelomonocytic leukemia cells and SR immunoblastic lymphoma cells with EC50 values of 95 and 135 nM respectively and demonstrating 200-fold selectivity over Pol II.1,2 Activates the DNA damage response.3 It induces a rapid accumulation of cytosolic DNA which results in upregulation of STING.4 Acts as a potent immunosuppressant inhibiting T cell-mediated alloimmunity and representing a novel class of immunosuppressant.5
Biochemicals & reagents
1138549-36-6
1 Drygin et al. (2011), Targeting RNA polymerase I with an oral small molecule CX-5461 inhibits ribosomal RNA synthesis and solid tumor growth; Cancer Res., 71 1418 2 Haddach et al. (2012), Discovery of CX-5461, the first direct and selective inhibitor of RNA polymerase I, for cancer therapeutics; ACS Med. Chem. Lett., 3 602 3 Sanij et al. (2020), CX-5461 activates the DNA damage response and demonstrates therapeutic efficacy in high-grade serous ovarian cancer; Commun., 11 2641 4 Cornelison et al. (2021), CX-5461 Treatment Leads to Cytosolic DNA-Mediated STING Activation in Ovarian Cancer; Cancers (Basel), 13 5056 5 Pan et al. (2022), CX-5461 is a potent immunosuppressant which inhibits T cell-mediated alloimmunity via p53-DUSP5; Res., 177 106120
RT
TARGET: RNA; STING -- PATHWAY: DNA damage -- RESEARCH AREA: Immunology -- DISEASE AREA: Cancer