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Efforts to develop metallo\u2010\u03b2\u2010lactamase (MBL) inhibitors require suitable screening platforms to allow the rapid determination of \u03b2\u2010lactamase activity and efficient inhibition. Unfortunately, the platforms currently available are not ideal for this purpose. Further progress in MBL inhibitor identification requires inexpensive and widely applicable assays. Herein the identification of an inexpensive and stable chromogenic substrate suitable for use in assays of clinically relevant MBLs is described. (6<jats:italic>R<\/jats:italic>,7<jats:italic>R<\/jats:italic>)\u20103\u2010((4\u2010Nitrophenoxy)methyl)\u20108\u2010oxo\u20107\u2010(2\u2010phenylacetamido)\u20105\u2010thia\u20101\u2010azabicyclo[4.2.0]oct\u20102\u2010ene\u20102\u2010carboxylic acid 5,5\u2010dioxide (CLS405) was synthesised in a three\u2010step protocol. CLS405 was then characterised spectroscopically, and its stability and kinetic properties evaluated. With a \u0394<jats:italic>\u03bb<\/jats:italic><jats:sub>max<\/jats:sub> value of 100\u2005nm between the parent and hydrolysis product, a higher analytical accuracy is possible with CLS405 than with commonly used chromogenic substrates. The use of CLS405 in assays was validated by MBL activity measurements and inhibitor screening that resulted in the identification of <jats:italic>N<\/jats:italic>\u2010hydroxythiazoles as new inhibitor scaffolds for MBLs. Further evaluation of the identified <jats:italic>N<\/jats:italic>\u2010hydroxythiazoles against a panel of clinically relevant MBLs showed that they possess inhibitory activities in the mid\u2010 to low\u2010micromolar range. The findings of this study provide both a useful tool compound for further inhibitor identification, and novel scaffolds for the design of improved MBL inhibitors with potential as antibiotics against resistant strains of bacteria.<\/jats:p>","DOI":"10.1002\/cmdc.201300350","type":"journal-article","created":{"date-parts":[[2013,10,25]],"date-time":"2013-10-25T15:16:38Z","timestamp":1382714198000},"page":"1923-1929","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Chromophore\u2010Linked Substrate (CLS405): Probing Metallo\u2010\u03b2\u2010Lactamase Activity and Inhibition"],"prefix":"10.1002","volume":"8","author":[{"given":"Anne","family":"Makena","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sander S.","family":"van\u2005Berkel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clarisse","family":"Lejeune","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond J.","family":"Owens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anil","family":"Verma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramya","family":"Salimraj","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Spencer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00fcrgen","family":"Brem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher J.","family":"Schofield","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,10,25]]},"reference":[{"key":"e_1_2_6_1_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00253-003-1274-y"},{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0017549"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkp256"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dks289"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.1980.0049"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciq179"},{"key":"e_1_2_6_7_2","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1042\/bj2950705","volume":"295","author":"Matagne A.","year":"1993","journal-title":"Biochem. 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