'Magic Berries' Pack Phorbol Punch

Could plant extracts still surprise us? "Magical rainforest berry kills tumors with single injection" read last month's FiercePharma headline. The Guardian reinforced the hype, narrowing down the berry's source (Queensland, Australia) and the compound: EBC-46*, promoted by local biotech QBiotics and tested by colleagues at the QIMR Berghofer Medical Research Institute.

Digging down to the PLoS One article behind the research, I uncovered the drug's structure and proposed mode of action. Now, where have I seen a compound like that before? Oh, right! Ingenol. Both compounds belong to the phorbol ester family, and both appear to activate protein kinase C, spurring tissue necrosis and tumor shrinkage when directly injected into mouse skin cancer lesions.

The authors indicate that they're preparing GMP product for Phase I human trials; whether that's derived from magical rainforest berries - or just plain process chemistry - hasn't been disclosed.
Stay tuned.

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*The published structure doesn't match the molecular weight (562.25 g/mol) the PLoS authors suggest, and no stereochemistry is specified. I'm guessing it's structurally similar to phorbol, and I've gently highlighted in red a hydrogen that's probably supposed to be a methyl group.

Scalable Ingenol? Phil Strikes Again!

Update: Want the inside scoop? Check out Open Flask!

I'm officially declaring it: Every 6-7 months, we should expect another huge molecule to fall to Phil & Co:

May 2011: Cortistatin
November 2011: Taxane Cores
May 2012: Ten Meroterpenoids.
December 2012: Ouabagenin

July 2013: Seen the latest* over at ScienceExpress? I think this scheme sums the whole thing up quite nicely:

And that's why it's in Science, kids...
Source: Baran Group | ScienceExpress

Ingenol falls! LEO Pharma, in collaboration with Scripps, may soon make gram-scale batches of ingenol analogs - something that used to take entire groups years to make. This paper cheers from so many different bleachers, I can't even count 'em all:

Total synthesis accesses trace plant metabolite!

Investment in basic research reaps huge Pharma dividends!

Imitating nature makes stitching together complex terpenes look easy!

Enzymes, Schmenzymes...

This paper really does have something for everyone. A volatile intermediate gumming up the works. A surprise crystallization. X-Ray structures. Some allenic Pauson-Khand reactions. A low-temp vinylogous pinacol rearrangement. Even some C-H activation / oxidation tossed in at the end.

If you want some more ingenol goodies, head on over to Chemistry World's fantastic write-up.
And, of course, join me on PhilWatch somewhere around January 2014...

*Thanks again to Brandon for a copy.