E-resources
Peer reviewed
-
Dong, Shuzhi; Zhao, Zhiqiang; Tang, Haiqun; Li, Guoqing; Pan, Jianping; Gu, Xin; Jiang, Jinlong; Xiao, Li; Scapin, Giovanna; Hunter, David N.; Yang, Dexi; Huang, Yuhua; Bennett, Frank; Yang, Shu-Wei; Mandal, Mihirbaran; Tang, Haifeng; Su, Jing; Tudge, Clare; deJesus, Reynalda Keh; Ding, Fa-Xiang; Lombardo, Matthew; Hicks, Jacqueline D.; Fischmann, Thierry; Mirza, Asra; Dayananth, Priya; Painter, Ronald E.; Villafania, Artjohn; Garlisi, Charles G.; Zhang, Rumin; Mayhood, Todd W.; Si, Qian; Li, Nianyu; Amin, Rupesh P.; Bhatt, Bhavana; Chen, Feifei; Regan, Christopher P.; Regan, Hillary; Lin, Xinjie; Wu, Jin; Leithead, Andrew; Pollack, Scott R.; Scott, Jack D.; Nargund, Ravi P.; Therien, Alex G.; Black, Todd; Young, Katherine; Pasternak, Alexander
Journal of medicinal chemistry, 03/2024, Volume: 67, Issue: 5Journal Article
The use of β-lactam (BL) and β-lactamase inhibitor combination to overcome BL antibiotic resistance has been validated through clinically approved drug products. However, unmet medical needs still exist for the treatment of infections caused by Gram-negative (GN) bacteria expressing metallo-β-lactamases. Previously, we reported our effort to discover pan inhibitors of three main families in this class: IMP, VIM, and NDM. Herein, we describe our work to improve the GN coverage spectrum in combination with imipenem and relebactam. This was achieved through structure- and property-based optimization to tackle the GN cell penetration and efflux challenges. A significant discovery was made that inhibition of both VIM alleles, VIM-1 and VIM-2, is essential for broad GN coverage, especially against VIM-producing P. aeruginosa. In addition, pharmacokinetics and nonclinical safety profiles were investigated for select compounds. Key findings from this drug discovery campaign laid the foundation for further lead optimization toward identification of preclinical candidates.
Author
Shelf entry
Permalink
- URL:
Impact factor
Access to the JCR database is permitted only to users from Slovenia. Your current IP address is not on the list of IP addresses with access permission, and authentication with the relevant AAI accout is required.
Year | Impact factor | Edition | Category | Classification | ||||
---|---|---|---|---|---|---|---|---|
JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
Select the library membership card:
If the library membership card is not in the list,
add a new one.
DRS, in which the journal is indexed
Database name | Field | Year |
---|
Links to authors' personal bibliographies | Links to information on researchers in the SICRIS system |
---|
Source: Personal bibliographies
and: SICRIS
The material is available in full text. If you wish to order the material anyway, click the Continue button.