Current studentsExisting staffContact us
 

Preclinical development of Ramizol, an antibiotic belonging to a new class, for the treatment of Clostridium difficile colitis

Simple item page
dc.contributor.authorRao, S.
dc.contributor.authorPrestidge, C.A.
dc.contributor.authorMiesel, L.
dc.contributor.authorSweeney, D.F.
dc.contributor.authorShinabarger, D.L.
dc.contributor.authorBoulos, R.A.
dc.date.issued2016
dc.descriptionData source: Supplementary information, http://www.nature.com/ja/journal/vaop/ncurrent/extref/ja201645x1.docx
dc.description.abstractAntibiotic-resistant bacteria is a major threat to human health and is predicted to become the leading cause of death from disease by 2050. Despite the recent resurgence of research and development in the area, few antibiotics have reached the market, with most of the recently approved antibiotics corresponding to new uses for old antibiotics, or structurally similar derivatives thereof. We have recently reported an in silico approach that led to the design of an entirely new class of antibiotics for the bacteria-specific mechanosensitive ion channel of large conductance: MscL. Here, we present the preclinical development of one such antibiotic, Ramizol, a first generation antibiotic belonging to that class. We present the lack of interaction between Ramizol and other mammalian channels adding credibility to its MscL selectivity. We determine the pharmacokinetic profile in a rat model and show <0.1% of Ramizol is absorbed systemically. We show this non-systemic nature of the antibiotic translates to over 70% survival of hamsters in a Clostridium difficile colitis model. Lastly, initial in vitro data indicate that resistance to Ramizol occurs at a low frequency. In conclusion, we establish the potential of Ramizol as an effective new treatment for C. difficile associated disease.
dc.identifier.citationJournal of Antibiotics, 2016; 69(12):879-884
dc.identifier.doi10.1038/ja.2016.45
dc.identifier.issn0021-8820
dc.identifier.issn1881-1469
dc.identifier.urihttps://hdl.handle.net/11541.2/122176
dc.language.isoen
dc.publisherNature Publishing
dc.relation.fundingBoulos & Cooper Pharmaceuticals
dc.rightsCopyright 2016 Nature Publishing This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivs 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by nc-nd/4.0/ (http://creativecommons.org/licenses/by nc-nd/4.0/)
dc.source.urihttp://dx.doi.org/10.1038/ja.2016.45
dc.subjectRamizol
dc.subjectantibiotic-resistance
dc.subjectClostridium difficile
dc.titlePreclinical development of Ramizol, an antibiotic belonging to a new class, for the treatment of Clostridium difficile colitis
dc.typeJournal article
pubs.publication-statusPublished
ror.fileinfo12143158730001831 13143154130001831 9916084094501831_53139149360001831.pdf
ror.mmsid9916084094501831

Files

Original bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
9916084094501831_53139149360001831.pdf
Size:
507.26 KB
Format:
Adobe Portable Document Format
Description:
Published version
Download

Collections