Biological Effects of Modifications of the Englerin A Glycolate

Sarath P.D. Seenadera, Sarah A. Long, Rhone Akee, Gabriela Bermudez, Gregory Parsonage, Jonathan Strope, Cody Peer, W. Douglas Figg, Kathlyn A. Parker, David J. Beech, John A. Beutler*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


Modifications at the glycolate moiety of englerin A were made to explore variations at the most sensitive site on the molecule for activity in the NCI 60 screen, wherein englerin A is highly potent and selective for renal cancer cells. Replacement of the glycolate by other functionalities as well as esterification of the glycolate hydroxyl yielded compounds which displayed excellent selectivity and potency compared with the natural product. TRPC4/5 ion channel experiments with five compounds showed delayed or reduced agonism with TRPC5, at much higher concentrations than englerin A. With TRPC4, these compounds all had no effect at 10 μM. The same compounds were not detectable in mouse serum after a single oral dose of 12.5 mg/kg. At 100 mg/kg p.o., no toxicity was observed, and blood levels were barely detectable. Intravenous administration led to toxicity but at substantially lower doses than for englerin A.

Original languageEnglish
Pages (from-to)1472-1476
Number of pages5
JournalACS Medicinal Chemistry Letters
Issue number9
StatePublished - 8 Sep 2022
Externally publishedYes


  • Analogues
  • Englerins
  • Renal cancer
  • Sesquiterpenes
  • TRPC4/5


Dive into the research topics of 'Biological Effects of Modifications of the Englerin A Glycolate'. Together they form a unique fingerprint.

Cite this