EBC-46 from Blushwood berry

[Graham49]

This has been posted on some time ago. Here is an update. No trial on PCa so far, I think.

Chemistry, mode of action and clinical efficacy of the anticancer diterpenoid tigilanol tigliate (EBC-46)

G Appendino1  Dipartimento di Scienze del Farmaco, Largo Donegani, 28100 Novara, Italy

A Pagani1  Dipartimento di Scienze del Farmaco, Largo Donegani, 28100 Novara, Italy

C Williams2  School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, Australia

J Cullen3  Drug Discovery Group, QIMR Berghofer Medical Research Institute, Brisbane, Australia

G Boyle3  Drug Discovery Group, QIMR Berghofer Medical Research Institute, Brisbane, Australia

P Parsons3  Drug Discovery Group, QIMR Berghofer Medical Research Institute, Brisbane, Australia

J Campbell4  QBiotics Group Ltd, Yungaburra, Queensland, Australia

V Gordon4  QBiotics Group Ltd, Yungaburra, Queensland, Australia

P Schmidt4  QBiotics Group Ltd, Yungaburra, Queensland, Australia

P Reddell4  QBiotics Group Ltd, Yungaburra, Queensland, Australia

› Author Affiliations

Further Information

Congress Abstract

Full Text

References

Figures

References

Tigilanol tiglate (EBC-46, 1), a novel diterpene ester isolated from the seeds of the endemic Australian rainforest tree Fontainea picrosperma (Euphorbiaceae), is being developed for intratumoral treatment of cancers in humans and companion animals [1],[2]. Here we summarise our current understanding of the chemistry and mechanism of action of the compound, and provide results from recently completed veterinary (Phase III) and human (Phase I/II) clinical trials.

Tigilanol tiglate has a multi-factorial mechanism of action. A single intratumoural injection (1) induces a rapid, highly localised and transient inflammatory response surrounding the tumour mass, (2) significantly increases permeability of the tumour vascular endothelium, and (3) causes rapid tumour cell death by oncosis. In combination, these result in tumour haemorrhagic necrosis, eschar formation and complete tumour destruction within 4 to 14 days. Localised inflammation and increasing permeability of tumour vasculature are associated directly with the activation by tigilanol tiglate of specific isoforms of protein kinase C (-βI, -βII, -α, -γ), while tumour cell death via oncosis requires PKC/C1 domain mediated signalling. The compound also induces changes in cytokine signalling and gene expression that promote wound healing following tumour destruction.

In a Phase III fully-randomised, controlled and blinded veterinary clinic trial, a single treatment with tigilanol tiglate resulted in complete and enduring tumour destruction in more than 75% of canine patients with mast cell tumours. In a clinical Phase I/II human dose-escalation study, maximum tolerated dose was not reached and signs of efficacy were observed in 9 tumour types, including complete response in 4 patients.

[j-o-h-n]

wtf thanks.. anyway...

Good Luck, Good Health and Good Humor.

j-o-h-n Tuesday 12/31/2019 7:01 PM EST

[JLS1]

I was just reading about EBC-46 while researching treatments for dogs with grade 3 mast cell tumors. It sounds very promising for solid tumors!

fwiw, Here's a link to earlier discussion here, 3 years ago:

healthunlocked.com/advanced...