Why is Rapamycin not a Rapalog?

Just to settle things on this issue:

Rapamycin (sirolimus) is an immunosuppressive drug approved by the Food and Drug Administration (FDA). It is also a leading candidate for targeting aging. Rapamycin and its analogs (everolimus, temsirolimus, ridaforolimus) inhibit the mammalian target of rapamycin (mTOR) kinase by binding to FK506-binding proteins (FKBP) and have a similar chemical structure that only differs in the functional group present at carbon-40. Analogs of rapamycin were developed to improve its pharmacological properties, such as low oral bioavailability and a long half-life. The analogs of rapamycin are referred to as ‘rapalogs.’ Rapamycin is the parent compound and should there with not be called a ‘rapalog.’


I don’t have the access to the full paper, what’s the conclusion of the paper? Do they compare the pro and con of Rapamycin (sirolimus) with other Raplogs? Do they conclude that sirolimus is superior than everolimus, temsirolimus, ridaforolimus? Or vice the versa?

I just bought many packs of evrolimus and still waiting the shipping from india, I finally decide to replace sirolimus with evrolimus due to its shorter half-life, and less disturbance of insulin sensitivity.

There are also price and shipping advantage of everolimus, everolimus is cheaper than sirolimus (per mg).

  • 1 pack of Siromus, 6tablets*1mg=6mg, total USD 6.8, average 6.8USD/6mg= 1.133 USD/mg
  • 1 pack of Everolimus, 7tablets*10mg=70mg, total USD 50, average 50USD/70mg= 0.714 USD/mg

Also, a bigger package of Everolimus means that you can bring more packs a time without detained by the customs(Sirolimus 6mg vs Everolimus 70mg in one pack). I don’t know if there are anyone also considering replacing Sirolimus with Everolimus, and any opinion is welcomed.


I agree with the advantages you list with sirolimus especially w.r.t the logistics w.r.t customs, shipping, traveling, etc.

I have in fact been using it recently. I felt the short half-life should definitely help.

My only concern is that there have not been enough studies with it for longevity outside of the Mannick paper. Do you happen to have found any particular literature that makes you more confident about using it?

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Are there mouse studies using everolimus?

The Everolimus molecule is virtually identical to the rapamycin molecule, and the researchers I’ve talked to, like Matt Kaeberlein, believe that they are effectively the same drug (the only reason everolimus was created was to get around the intellectual property patents that Pfizer held on rapamycin/sirolimus).

I do like the higher dose tablets of rapamycin and plan to use Everolimus in the future, possibly alternating between it and rapamycin just to balance any of the minor differences between the two.

There are no longevity-oriented mouse studies using everolimus, that I’m aware of. It would probably be impossible to get funding for something like that because rapamycin is so well studied and the difference between the two molecules is so small.

There is a new everolimus human longevity clinical study being started soon by Adam Konopka at the University of Wisconsin - so we’ll eventually get more data. Full details and interview, with lots of good info on rapamycin and everolimus in this interview: Rapamycin and Beyond: Presentation by Dudley Lamming & Adam Konopka

More reading on everolimus here:


No - this is just a clarification on the nomenclature around rapamycin and rapalogs. Some researchers like Blagosklonny have referred to the general class of all of these molecules (rapamycin and all the similar molecules; e.g. everolimus, temsirolimus, etc.) as rapalogs. But that is wrong - because rapamycin was identified first. Then people created new drugs that “act like” rapamycin and are extremely similar from a chemical structure standpoint. The point of the paper above is that only these follow-on drugs are rapalogs because it is those drugs that were developed later to “act like/look like” rapamycin.

The net take-away here is there is rapamycin. And there are a few other drugs called “rapalogs” that function the same as rapamycin to block mTOR.


My decision of choosing Everolimus is mainly due to the short half-life time, however I didn’t find particular convincing evident that Everolimus is over Sirolimus in longevity purpose.

I think the strategy of alternating between Everolimus and Sirolimus is a good way as RapAdmin mentioned.

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