Identification of Novel Carbonic Anhydrase IX Inhibitors Using High-Throughput Screening of Pooled Compound Libraries by DNA-Linked Inhibitor Antibody Assay (DIANA)

0540277 - ÚMG 2021 RIV US eng J - Journal Article
Tykvart, J. - Navrátil, V. - Kugler, Michael - Šácha, P. - Schimer, J. - Hlaváčková, A. - Tenora, L. - Zemanová, J. - Dejmek, M. - Král, Vlastimil - Potáček, M. - Majer, P. - Jahn, U. - Brynda, Jiří - Řezáčová, Pavlína - Konvalinka, J.
Identification of Novel Carbonic Anhydrase IX Inhibitors Using High-Throughput Screening of Pooled Compound Libraries by DNA-Linked Inhibitor Antibody Assay (DIANA).
SLAS Discovery. Roč. 25, č. 9 (2020), s. 1026-1037. ISSN 2472-5552. E-ISSN 2472-5560
Institutional support: RVO:68378050
Keywords : high-throughput screening * carbonic anhydrase IX * drug discovery * DNA-linked inhibitor antibody assay
OECD category: Biochemistry and molecular biology
Impact factor: 2.918, year: 2020
Method of publishing: Limited access
https://journals.sagepub.com/doi/10.1177/2472555220918836

The DNA-linked inhibitor antibody assay (DIANA) has been recently validated for ultrasensitive enzyme detection and for quantitative evaluation of enzyme inhibitor potency. Here we present its adaptation for high-throughput screening of human carbonic anhydrase IX (CAIX), a promising drug and diagnostic target. We tested DIANA's performance by screening a unique compound collection of 2816 compounds consisting of lead-like small molecules synthesized at the Institute of Organic Chemistry and Biochemistry (IOCB) Prague ('IOCB library'). Additionally, to test the robustness of the assay and its potential for upscaling, we screened a pooled version of the IOCB library. The results from the pooled screening were in agreement with the initial nonpooled screen with no lost hits and no false positives, which shows DIANA's potential to screen more than 100,000 compounds per day.
Permanent Link: http://hdl.handle.net/11104/0317971