Comment by dnautics | Hacker News Reader

Comment by dnautics | Hacker News Reader

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well we are trying to stack the deck in the drug's favor. A few things:

1) it's a "natural product derivative". These compounds do way way better than most other drug classes.

2) it has single-digit nanomolar activity in the dish. This is on-par and competitive with currently used chemotherapeutics, a prerequisite for any sort of chemotherapy.

3) there is another compound in the same family called SJG-136 which has passed phase II.

4) phase I trials for SJG-136 apparently showed extremely mild side effects. I still need to double-check clinicaltrials.gov on this, this was a personal communication from the developer of SJG-136. Because SJG-136 and 9DS broadly share the same mechanism it's very likely that 9DS will also have mild side effects.

To answer ThomPete's question, I'm not sure how I can verify this besides "trust me" to the layperson (especially #4). However, there is literature on #1 and #2, although, again I'm not sure how useful this is to the lay person.

#1: http://onlinelibrary.wiley.com/doi/10.1111/j.1751-7915.2010....

#2: https://www.ncbi.nlm.nih.gov/pubmed/22390171

Thanks I will have a look and just to be clear, I trust your intend 100%.

I have been lucky enough to be accepted at Sloan Memorial en New York given I have more than a thousand moles.

I wonder if I could ask my dermatologist there.

Yes, but don't all pharma researchers "stack their decks" in similar ways, to maximize their chance of success? And still fail with the dismal statistics I linked to?

yes and no.

For example, the trend now is toward maintenance drugs and biologicals, because that's what the execs want. Whether or not this has anything to do with efficacy is questionable. During my biophysics days, I saw so many drugs enter the clinical pipeline even purporting to treat alzheimers, that were basically following up on "popular memes in the field" that from first principles I would look at and say, there's no way this will work.

I've spoken to one pharma consultant (to get the chat, I didn't tell him I was making an unpatented drug) who basically lamented what had happened to the cancer field as the big companies lost their R&D and turned to acquiring biotechs for their blue sky stuff - and he characterized biotechs as being on to "fad-dey" stuff. Now, it's alos possible that he's wrong too, and that I'm on the wrong track. So you are correct to worry about the likelihood of success.

I don't know how bad pharma politics are, but I have hard time imagining they're worse than crowdfunding! I think no one on this site really understands what you're doing. We know you're more credible than a homeopathic scam artist, which is to our credit because the broader crowdfunding demographic is unlikely to figure out the difference. (See fig. 1, sales of homeopathic remedies in billion USD). But would you trust us to figure out that your compound is more promising than some other one, with similar-looking technical jargon, proposed by similarly credentialed researchers?

I think the concept is incredibly radical. If this were a business idea, it would be functionally illegal: you could only solicit funding from wealthy, accredited investors under highly regulated procedures. Because people are easily mislead. And that's for stupid things like selling sporks. But here we are, pretending to scrutinize a million-dollar medical research grant, as if we were PhDs at the NIH office or something. Where do you want to go with this?

Is your presupposition that the TLAs are better at this than you are? There's a huge project right now at DARPA (https://www.fbo.gov/index?s=opportunity&mode=form&id=0d71fc7...) that is being led by program manager whose graduate work is increasingly suspected of being completely artefactual. http://raphazlab.wordpress.com/2012/12/11/seven-years-of-ima...

Just FYI, I wouldn't put too much faith in safety profiles of related family drugs. The classic med chem example of really unpredictable toxicology is mevastatin vs lovastatin, which have exactly the same structure but for one lowly methyl group. The former molecule was basically an unusably toxic drug candidate that never would have been approved by the FDA, whereas the latter was the first safe and effective statin to go to market.

it's a known mechanistic issue. the pyrrolobenzodiazepine molecules are pretty selective DNA alkylators. Cardiotox is caused probably by transport chain involvement when the 9-position is oxygenated (makes it look like Co-Q). Without that oxygen, the PBDs zip on over to the DNA. PBDs have a slight twist to the molecule which allows them to nestle in the minor groove with exactly the right pitch so that the lesion evades base excision repair response, which is what is thought to cause the more serious side effects in DNA-alkylating chemotherapies.

However, you are right, there could be unforseen toxicity issues.

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