Identification of Inhibitors of virus nsP2 ATPase.

Non-structural protein 2 (nsP2), which plays an essential role in replication of CHIKV, contains a protease, helicase, and methyltransferase-like domain. We executed a simple a screen using malachite green to detect compounds that decreased ATP hydrolysis and tested a library of diverse compounds to find inhibitors of CHIKV nsP2 helicase.

Toward target 2035: EUbOPEN - a public-private partnership to enable & unlock biology in the open.

Target 2035 is a global initiative that seeks to identify a pharmacological modulator of most human proteins by the year 2035. As part of an ongoing series of annual updates of this initiative, we summarise here the efforts of the EUbOPEN project whose objectives and results are making a strong contribution to the goals of Target 2035. EUbOPEN is a public-private partnership with four pillars of activity: (1) chemogenomic library collections, (2) chemical probe discovery and technology development for hit-to-lead chemistry, (3) profiling of bioactive compounds in patient-derived disease assays, and (4) collection, storage and dissemination of project-wide data and reagents.

A Covalent Chemical Probe for nsP2 Cysteine Protease with Antialphaviral Activity and Proteome-wide Selectivity.

RA-0003022 () was identified as a high-quality covalent chemical probe for nsP2 cysteine protease (nsP2pro). Isoxazole covalently captured the active site C478 and inactivated the enzyme with a / ratio of 6000 Ms. A negative control analog RA-0025453 () retained the covalent warhead but demonstrated >100-fold decrease in enzyme inhibition.

SeHCAT retention measurements may be compromised by traces of 177 Lu/ 177m Lu more than 90 days after 177 Lu-DOTATATE was administered.

[ 75 Se]tauroselcholic acid (SeHCAT) retention measurement provides a noninvasive test for bile acid diarrhea (BAD); however, it is sensitive to the presence of other radionuclides. Two SeHCAT patients at the Royal Free Hospital (RFH) had significant discrepancies between the lower photopeak (111-159 keV) and central photopeak (242-296 keV) windows, indicating contamination with a radionuclide other than 75 Selenium. These patients had received lutetium-177 oxodotreotide ( 177 Lu-DOTATATE) therapy 98 and 151 days before their SeHCAT tests.