1138549-36-6 Usage
Uses
Used in Cancer Treatment:
CX-5461 is used as an anti-cancer agent for its ability to selectively inhibit RNA polymerase I-mediated pre-rRNA transcription, which is essential for the proliferation of cancer cells. It has shown effectiveness in inhibiting Pol I-dependent proliferation in various cancer cell lines and suppressing tumor expansion in vivo.
Used in Pharmaceutical Research:
CX-5461 is used as a research tool for studying the role of RNA polymerase I in cancer cell proliferation and the potential of targeting this pathway for therapeutic intervention. Its selective inhibition of pre-rRNA transcription makes it a valuable compound for understanding the underlying mechanisms of cancer cell growth and identifying new targets for cancer treatment.
Used in Drug Development:
CX-5461 is used in the development of new cancer therapies, as its mechanism of action provides a unique approach to targeting cancer cell proliferation. Its effectiveness in inhibiting Pol I-dependent proliferation and suppressing tumor expansion in vivo makes it a promising candidate for further research and potential clinical application in cancer treatment.
Biological Activity
cx-5461 is a potent and orally bioavailable small-molecule inhibitor of rrna synthesis that specifically inhibits rna polymerase (pol) i-driven transcription with ic50 value of 142 nm. cx-5461 exhibits antiproliferative activity against human pancreatic tumor cells mia paca-2, human melanoma cells a375 and colorectal carcinoma cells hct-116 with ec50 values of 74, 58, and 167 nmol/l, respectively. [1].cx-5461 was revealed to inhibit pol i transcription via promoting the stabilization of p53. in addition, cx-5461 has been demonstrated to induce autophagy and senescence but not apoptosis in mia paca-2 and a375 cell lines.
Biochem/physiol Actions
Cell permeable: yes
in vivo
cx-5461 has shown to suppress tumor volume in both mia paca-2 and a375 derived xenograft mice models [1].
references
[1] drygin d1, lin a, bliesath j, ho cb, o'brien se, proffitt c, omori m, haddach m, schwaebe mk, siddiqui-jain a, streiner n, quin je, sanij e, bywater mj,hannan rd, ryckman d, anderes k, rice wg. 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
Check Digit Verification of cas no
The CAS Registry Mumber 1138549-36-6 includes 10 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 7 digits, 1,1,3,8,5,4 and 9 respectively; the second part has 2 digits, 3 and 6 respectively.
Calculate Digit Verification of CAS Registry Number 1138549-36:
(9*1)+(8*1)+(7*3)+(6*8)+(5*5)+(4*4)+(3*9)+(2*3)+(1*6)=166
166 % 10 = 6
So 1138549-36-6 is a valid CAS Registry Number.
1138549-36-6Relevant articles and documents
CRYSTALLINE FORMS OF QUINOLINE ANALOGS AND SALTS THEREOF, COMPOSITIONS, AND THEIR METHODS FOR USE
-
Paragraph 0244-0254, (2021/02/19)
The present invention includes crystalline forms of 2-(4-Methyl-[1,4]diazepan-1-yl)-5-oxo-5H-7-thia-1,11b-diaza-benzo[c]fluorene-6-carboxylic acid (5-methyl-pyrazin-2-ylmethyl)-amide (Compound I). Furthermore, the present invention provides compositions comprising the crystalline forms and therapeutic use of the crystalline forms and the compositions thereof.
Discovery of CX-5461, the first direct and selective inhibitor of RNA polymerase I, for cancer therapeutics
Haddach, Mustapha,Schwaebe, Michael K.,Michaux, Jerome,Nagasawa, Johnny,O'Brien, Sean E.,Whitten, Jeffrey P.,Pierre, Fabrice,Kerdoncuff, Pauline,Darjania, Levan,Stansfield, Ryan,Drygin, Denis,Anderes, Kenna,Proffitt, Chris,Bliesath, Josh,Siddiqui-Jain, Adam,Omori, May,Huser, Nanni,Rice, William G.,Ryckman, David M.
, p. 602 - 606 (2012/10/08)
Accelerated proliferation of solid tumor and hematologic cancer cells is linked to accelerated transcription of rDNA by the RNA polymerase I (Pol I) enzyme to produce elevated levels of rRNA (rRNA). Indeed, upregulation of Pol I, frequently caused by mutational alterations among tumor suppressors and oncogenes, is required for maintenance of the cancer phenotype and forms the basis for seeking selective inhibitors of Pol I as anticancer therapeutics. 2-(4-Methyl-[1,4]diazepan-1-yl)-5-oxo-5H-7-thia-1,11b-diaza-benzo[c] fluorene-6-carboxylic acid (5-methyl-pyrazin-2-ylmethyl)-amide (CX-5461, 7c) has been identified as the first potent, selective, and orally bioavailable inhibitor of RNA Pol I transcription with in vivo activity in tumor growth efficacy models. The preclinical data support the development of CX-5461 as an anticancer drug with potential for activity in several types of cancer.
Facile and efficient generation of quinolone amides from esters using aluminum chloride
Schwaebe, Michael K.,Ryckman, David M.,Nagasawa, Johnny Y.,Pierre, Fabrice,Vialettes, Anne,Haddach, Mustapha
scheme or table, p. 1096 - 1100 (2011/03/22)
Quinolone esters are readily converted into the corresponding amides using aluminum chloride at room temperature in excellent yields and purities. The method is both general and scalable to multi-kilogram quantities.
QUINOLONE ANALOGS AND METHODS RELATED THERETO
-
Page/Page column 135; 136, (2009/04/24)
The present invention provides novel quinolone compounds and pharmaceutical composition thereof which may inhibit cell proliferation and/or induce cell apoptosis. The present invention also provides methods of preparing such compounds and compositions, and methods of making and using the same.
