Discovery of CA9–005 as a new carbonic anhydrase 9 inhibitor using a DNA encoded-libraries

This study utilized DNA-encoded library (DEL) screening to identify novel inhibitors of carbonic anhydrase 9 (CA9), a key cancer target. Among the identified compounds, CA9–005 exhibited strong inhibitory activity and reduced cancer cell viability while CA9–061 and CA9–062 showed high binding affinities but limited enzymatic inhibition. Biolayer interferometry confirmed CA9–005's direct interaction with CA9, supported by structural modeling. These findings highlight the potential of DEL screening for drug discovery and establish CA9–005 as a promising anticancer candidate, warranting further structural and therapeutic optimization. • CA9 is a promising target for cancer therapy due to its tumor-specific expression. • DEL technology enables high-throughput screening of CA9 inhibitors efficiently. • CA9–005 showed strong CA9 binding, enzymatic inhibition, and anticancer activity. • Structural analysis confirmed CA9–005's interaction within the catalytic cleft. • DEL screening accelerates drug discovery, enhancing efficiency and cost-effectiveness.

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Publication Details

Journal
Results in Chemistry
Published
2025-06-16
DOI
https://doi.org/10.1016/j.rechem.2025.102455
Primary Topic
Enzyme function and inhibition
Type
article
Field-Weighted Citation Impact
0.00

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article

Discovery of CA9–005 as a new carbonic anhydrase 9 inhibitor using a DNA encoded-libraries

Jung‐Nyoung Heo, Jeonghui Im, Shujuan Yu, Byumseok Koh et al.
Results in Chemistry
Enzyme function and inhibition
article

Discovery of CA9–005 as a new carbonic anhydrase 9 inhibitor using a DNA encoded-libraries

Jung‐Nyoung Heo, Jeonghui Im, Shujuan Yu, Byumseok Koh, Yuno Lee, Sung Bum Park, Ju Ho Lee, Byungho Lim, Nam‐Chul Cho, Doyoun Kim, Daesoo Kim, Hyun Jin Kim, Jiwoo Kim, Kyoung Jin Choi, Ki Young Kim, Byungwook Lee
article en

Abstract

This study utilized DNA-encoded library (DEL) screening to identify novel inhibitors of carbonic anhydrase 9 (CA9), a key cancer target. Among the identified compounds, CA9–005 exhibited strong inhibitory activity and reduced cancer cell viability while CA9–061 and CA9–062 showed high binding affinities but limited enzymatic inhibition. Biolayer interferometry confirmed CA9–005's direct interaction with CA9, supported by structural modeling. These findings highlight the potential of DEL screening for drug discovery and establish CA9–005 as a promising anticancer candidate, warranting further structural and therapeutic optimization. • CA9 is a promising target for cancer therapy due to its tumor-specific expression. • DEL technology enables high-throughput screening of CA9 inhibitors efficiently. • CA9–005 showed strong CA9 binding, enzymatic inhibition, and anticancer activity. • Structural analysis confirmed CA9–005's interaction within the catalytic cleft. • DEL screening accelerates drug discovery, enhancing efficiency and cost-effectiveness.

Results in ChemistryVol. 16
Chungnam National University (KR), Korea Research Institute of Chemical Technology (KR), Korea Research Institute of Bioscience and Biotechnology (KR), Korea University of Science and Technology (KR)
National Research Foundation, Korea Research Institute of Chemical Technology
Openalex Percentile: Top 87%
Enzyme function and inhibition
DOIOpen Access PDFOpenAlex
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