Inhibitory activity against carbonic anhydrase IX and XII as a candidate selection criterion in the development of new anticancer agents

Mikhail Krasavin; Stanislav Kalinin; Tatiana Sharonova; Claudiu T Supuran

doi:10.1080/14756366.2020.1801674

Inhibitory activity against carbonic anhydrase IX and XII as a candidate selection criterion in the development of new anticancer agents

J Enzyme Inhib Med Chem. 2020 Dec;35(1):1555-1561. doi: 10.1080/14756366.2020.1801674.

Authors

Mikhail Krasavin¹, Stanislav Kalinin¹, Tatiana Sharonova¹, Claudiu T Supuran²

Affiliations

¹ Institute of Chemistry, St. Petersburg State University, St. Petersburg, Russia.
² Neurofarba Department, Section of Pharmaceutical Sciences, University of Florence, Florence, Italy.

Abstract

Analysis of the literature data reveals that while inhibition of cancer-related carbonic anhydrase IX and XII isoforms continues to be an important enrichment factor for designing anticancer agent development libraries, exclusive reliance on the in vitro inhibition of these two recombinant isozymes in nominating candidate compounds for evaluation of their effects on cancer cells may lead not only to identifying numerous compounds devoid of the desired cellular efficacy but also to overlooking many promising candidates which may not display the best potency in biochemical inhibition assay. However, SLC-0111, now in phase Ib/II clinical trials, was developed based on the excellent agreement between the in vitro, in vivo and more recently, in-patient data.

Keywords: Carbonic anhydrase inhibitors; anticancer agents; cancer-related IX and XII isoforms; enrichment factor; screening funnel.

MeSH terms

Antigens, Neoplasm
Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Carbonic Anhydrase IX
Carbonic Anhydrase Inhibitors / chemical synthesis
Carbonic Anhydrase Inhibitors / chemistry
Carbonic Anhydrase Inhibitors / pharmacology*
Carbonic Anhydrases
Cell Line, Tumor
Cell Proliferation / drug effects
Dose-Response Relationship, Drug
Drug Development*
Drug Screening Assays, Antitumor
Humans
Molecular Structure
Structure-Activity Relationship

Substances

Antigens, Neoplasm
Antineoplastic Agents
Carbonic Anhydrase Inhibitors
CA9 protein, human
Carbonic Anhydrase IX
Carbonic Anhydrases
carbonic anhydrase XII

Grants and funding

This research was supported by the Russian Federation Government Megagrant 14.W03.031.0025. Tatiana Sharonova is grateful to the Russian Foundation for Basic Research for the graduate student research grant (project 19-33-90017).