Identification of an (-)-englerin A analogue, which antagonizes (-)-englerin A at TRPC1/4/5 channels.

ABSTRACT:

Background and purpose

(-)-Englerin A (EA) is a potent cytotoxic agent against renal carcinoma cells. It achieves its effects by activation of transient receptor potential canonical (TRPC)4/TRPC1 heteromeric channels. It is also an agonist at channels formed by the related protein, TRPC5. Here, we sought an EA analogue, which might enable a better understanding of these effects of EA.

Experimental approach

An EA analogue, A54, was synthesized by chemical elaboration of EA. The effects of EA and A54 on the activity of human TRPC4 or TRPC5 channels overexpressed on A498 and HEK 293 cells were investigated, firstly, by measuring intracellular Ca²⁺ and, secondly, current using whole-cell patch clamp recordings.

Key results

A54 had weak or no agonist activity at

SUBMITTER: Rubaiy HN 

PROVIDER: S-EPMC5811624 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature