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Englerin-A

Agonist of TRPC4, TRPC5

Structure

Information

  • TRPC4
  • TRPC5
  • Agonist

In Vitro Validations

No in Vitro Validations

In Cell Validations

In Vivo Data

No in Vivo Validations

Off-Target Selectivity Assesments

Probe Selectivity in Vitro:
Englerin A (1 µM) was assayed for inhibition of selected protein kinases (SelectScreen Kinase Profling), GPCRs (GPCRProfiler® services of EMD Millipore) and ion channels (Ion Channel Profiler Services of EMD Millipore). Only weak activity was observed against some of these proteins: ca. 30% inhibition of GPR109A and 15% inhibition of hERG.
Potency assay, off target (cells): No (agonistic) activity of Englerin A was detected in HEK293 cells overexpressing TRPC6, TRPM2 or TRPV4. The activity was assessed based on Ca2+ level measurements at a compound concentration of 1 µM.
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SERP ratings and comments

SERP Ratings

In Cell Rating
In Model Organisms

SERP Comments:

Cytotoxicity was observed at 17 nM and 45 nM at different timepoints. Cell EC50s for TRPC4 and TRPC5 are 11 nM and 8 nM, respectively; therefore, there is an insufficient window between on-target activity and cytotoxicity to interpret cellular effects of the compound as target-based.

(last updated: 10 Mar 2017 )

SERP Ratings

In Cell Rating

SERP Comments:

There have been several papers showing that this compound activates TRPC4/5 including doi: 10.1002/anie.201411511. The data in those papers is quite convincing that the compound at low nM concentrations activates these channels and that it may mediate some of its anti-tumor activity via this effect. However, there is no convincing dataset regarding potential off-targets, as it has not yet been broadly screened against kinases, GPCRs, ion channels, and so on. Thus, provided the user does the appropriate controls (e.g., TRPC4/5 KO cells as a control), the compound will likely be useful.

(last updated: 20 Mar 2017 )

SERP Ratings

In Cell Rating

(last updated: 26 Apr 2017 )