Carbonic anhydrase inhibitors as emerging agents for the treatment and imaging of hypoxic tumors.

Carbonic anhydrase inhibitors as emerging agents for the treatment and imaging of hypoxic tumors. Expert Opin Investig Drugs. 2018 Nov 14;: Authors: Supuran CT Abstract INTRODUCTION: Hypoxic tumors overexpress two carbonic anhydrases (CA, EC 4.2.1.1), CA IX and XII, involved in complex processes connected to tumorigenesis (pH regulation, metabolism, invasion and dissemination of the tumor). The biochemical rationale behind these processes is orchestrated by the transcription factor hypoxia inducible factor 1 (HIF-1). Areas covered. CA IX and XII have been validated as antitumor/antimetastatic drug targets and may be used for imaging hypoxic tumors. Many CA inhibitors (CAIs) selectively inhibit two isoforms belonging to the sulfonamide, coumarin and sulfocoumarin classes. CA IX/XII inhibitors inhibit the growth of primary tumors and the formation of metastases and deplete the cancer stem cell population, alone or in combination with other agents. These are three beneficial antitumor mechanisms that make them unique among anticancer drugs available. Expert commentary. Indisulam entered clinical trials as an antitumor sulfonamide; it progressed to Phase II trials but was terminated in 2016. However, SLC-011, a sulfonamide CA IX/XII inhibitor 1, recently completed a successful Phase I clinical trial for the treatment of advanced, metastatic solid tumors. This compound is now in Phase Ib/II clinical trials and is being assessed as a monot...
Source: Expert Opinion on Investigational Drugs - Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research