AOD-9604 and the fragment hypothesis, revisited

Posting this under the heading it deserves: AOD-9604 and the fragment hypothesis, revisited Everything below is what sits behind that.

Comparing SURPASS-2 (N Engl J Med, 2021) with SUSTAIN 6 (N Engl J Med, 2016) and finding the comparison harder than it looks.

Different populations, different durations, different endpoints defined slightly differently, and in one case a different estimand. People compare the headline percentages anyway, including me until recently.

Is there a defensible way to put these side by side, or is the honest answer that there is not and we should stop?

Worth separating two things that the opening post runs together.

Why catalogue breadth is not evidence of anything: a supplier listing 500 compounds does not make the 450 untested ones likely to work. It makes them untested compounds with supplier pages.

How to research a compound with no human data: mechanistic plausibility is one input. Preclinical data is another. The honest position is that you are reasoning from theory, not from evidence, and the track record of such reasoning is unimpressive when tested against actual outcomes.

Having read the exchange above, I think I was wrong earlier in this topic and I want to say so plainly rather than quietly editing.

The correction was fair and I had been repeating something I had not checked carefully enough.

post #4 answers the question as asked. The question underneath it is different.

Naming conventions for research peptides cause confusion because suppliers do not follow a standard. The same compound gets different names from different suppliers. If you are researching something, confirming the sequence or mass is more reliable than confirming the name.

Sequence verification: for an obscure compound, a report of the amino acid sequence or a mass-spectrometry result confirming the mass is the only verification that actually matters. A supplier's certificate stating the name is not verification.

Reading a supplier's product description as a marketing document: that is exactly what it is. The hyperbole, the mechanism written as fact, the theoretical benefits stated as established benefits — all of that is marketing. Treat it as such and separate it from evidence where evidence exists.

Compounds this community declines to help with, and why: there are specifics in the guidelines and they are not arbitrary. They exist because of failure modes that have happened in real people, not because of prudishness.

I disagree with the reply above, and I think the disagreement is substantive rather than terminological.

The distinction being drawn does not survive when you look at the published data for this specific question. I would be glad to be shown wrong on this, because the version I am arguing against is more convenient.

When "no data" is the complete and final answer: if there is no published human data on a compound, that is the state of knowledge. Hope is not a substitute and reasoning from theory is not a substitute. That is not a reason for shame; it is the honest epistemic position.

I read post #9 twice before replying, because I had assumed the opposite.

This subcategory exists because some people will research compounds outside the main groups discussed here. The standard of evidence and honesty about its limits applies to everything discussed, not just to approved drugs.

Distinguishing marketed research compounds from true chemical synthesis: some online suppliers sell compounds that are genuinely novel and difficult to obtain elsewhere. Others repackage standard compounds. Verifying what you are buying requires careful documentation review.

Research-use-only status is a legal classification, not a safety classification. It means the compound is sold for laboratory use and not for human consumption or treatment. The label does not tell you whether the molecule is safe, efficacious, or what its effects are.

post #13 is right about the mechanism and I think understates the practical bit.

Thank you for the correction. I have edited my earlier post with a note rather than silently, so the thread still makes sense to read. The error was mine and it was the kind that comes from remembering a figure instead of looking it up.