Rapid Parallel Screening for Strain Optimization

2013 ◽  
Author(s):  
Chuck Merryman ◽  
Tony Yee
2021 ◽  
Vol 14 (3) ◽  
pp. 203 ◽  
Author(s):  
Shurong Hou ◽  
Juan Diez ◽  
Chao Wang ◽  
Christoph Becker-Pauly ◽  
Gregg B. Fields ◽  
...  

Meprin α and β are zinc-dependent proteinases implicated in multiple diseases including cancers, fibrosis, and Alzheimer’s. However, until recently, only a few inhibitors of either meprin were reported and no inhibitors are in preclinical development. Moreover, inhibitors of other metzincins developed in previous years are not effective in inhibiting meprins suggesting the need for de novo discovery effort. To address the paucity of tractable meprin inhibitors we developed ultrahigh-throughput assays and conducted parallel screening of >650,000 compounds against each meprin. As a result of this effort, we identified five selective meprin α hits belonging to three different chemotypes (triazole-hydroxyacetamides, sulfonamide-hydroxypropanamides, and phenoxy-hydroxyacetamides). These hits demonstrated a nanomolar to micromolar inhibitory activity against meprin α with low cytotoxicity and >30-fold selectivity against meprin β and other related metzincincs. These selective inhibitors of meprin α provide a good starting point for further optimization.


Lung Cancer ◽  
2015 ◽  
Vol 87 (2) ◽  
pp. 122-129 ◽  
Author(s):  
Philipp Jurmeister ◽  
Dido Lenze ◽  
Erika Berg ◽  
Stefanie Mende ◽  
Frank Schäper ◽  
...  

2013 ◽  
Vol 7 (1) ◽  
pp. 29 ◽  
Author(s):  
Mona Yousofshahi ◽  
Michael Orshansky ◽  
Kyongbum Lee ◽  
Soha Hassoun
Keyword(s):  

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