I’m glad @Joseph is happy to take the risks and experiment on behalf of the rest of us and I hope he will share his results.
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We discussed trametinib earlier, here:
Cost is prohibitive (for me), based on Joseph’s own post.
I did a search in the India Pharmacy Pharmaceutical Market.
₹ 78,000
At today’s ( 02/18/2023) Exchange Rate cost is $942.42
I opined that myricetin is a MEK inhibitor; but it only inhibits MEK1, unlike trametinib (MEK1 and MEK2).
Sandra Kaufmann also says dihydromyricetin is a Sirt3 activator.
Minute 18:14
Original paper is below:
https://www.pnas.org/doi/10.1073/pnas.1913212116
In organisms ranging from invertebrates to mammals, reducing the activity of the nutrient-sensing mechanistic target of rapamycin (mTOR) and insulin/insulin-like growth factor signaling (IIS) network can promote longevity and health during aging (2, 3).
Lowering network activity can also protect against the pathology associated with genetic models of age-related diseases (1, 2). The network contains many drug targets, including mTOR, mitogen-activated protein kinase kinase (MEK), and glycogen synthase kinase-3 (GSK-3) (Fig. 1A).
Down-regulation of mTOR activity by rapamycin, GSK-3 by lithium, or MEK by trametinib can each individually extend lifespan in laboratory organisms (5–11),
and brief inhibition of mTOR has recently been shown to increase the response of elderly people to immunization against influenza (12). In addition, both mTOR and MEK inhibitors have been shown to reduce senescent phenotypes in human cells (13),
while increasing concentrations of lithium levels in drinking water correlate with reduced all-cause mortality in a Japanese population (10).
So mTOR inhibition, MEK inhibition, and lithium supplementation is the approach.
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Would you take rapamycin everyday for longevity?
Most likely not.
In my view trametinib is the same.
I will not be taking trametinib everyday.
Like rapamycin once a week.
Planning strategy, all subject to change.
Anyone besides myself considering trying the three compounds?
Rapamycin
Lithium Orotate
Trametinib
“If you wait until you are ready, it is almost certainly too late.”
~Seth Godin
“Keep waiting till you are ready and your time waiting will be gone forever. You will never get that time back.”
~Joseph
“I am not the waiting type.”
~Joseph
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Are you thinking of buying it from China?
No, looking at India and/or considering API mix in capsules.
It’ll become costly if you plan on using it for an extended period.
30 2mg tablet cost around $900.00 plus shipping from India
I would have preferred buying a few grams from a reliable Chinese supplier and then having it third-party tested. The drug has high oral bioavailability.
Do you know of someone?
Ask them.
WhatsApp +86 16621006118
Or:
WhatsApp +86 2784888682
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So I’m very interested in all this, particularly a lithium-rapa combo since my studies show the main issue with rapa and cancer is ubiquination mediated by GSK-3 preventing mtor inhibition in cancer.
However, I’m very wary of MEK inhibitors as I started taking dihydromyricetin high dose (2 grams) in January of this year and it seemed to cause profound skin aging effects that are only recently starting to go away.
I took dihydromyricetin years ago and didn’t have these problems.
I’m still wary of lithium until more research.
But all these molecules have long history of supplementation so like with many things - it appears the dose makes the poison. 
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At what interval?
2g every?
My thoughts are like take rapamycin for longevity weekly
Starting 2g a week of trametinib to start
Are you taking 2g a day for treatment for?
Do not take trametinib for longevity purposes. I worked on synthetic lethal chemo combinations in cancer at a startup for years. We tested this compound and it is not a good idea. The Erk pathway is very important for most epithelial cells. Stick to low risk acarbose and rapamycin combinations and do not consider trametinib. If you have melanoma or another type of solid tumor type then you could consider trametinib. Just trying to prevent you from causing long term damage.
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@Livin @Vlasko Thanks for sharing this vital piece of information. You may have just saved a few people from making a dangerous mistake.
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Livin, if you have reference to published paper please provide.
The problem is most targeted protein kinase inhibitor clinical trials are done in patients that failed first line chemo so this is a drug population that can’t be studied long term since they often have less than a year to live. I expect most long term side effects are not documented. The side effect profile does not look promising for a drug used for longevity purposes. The study of combination longevity effect also observed a significant reduction of fecundity so I hope you do not plan on having children. This is presumably also going to be combined with rapa which is also known to reduce fecundity. So I will restate that MEKi drugs all around are a bad class of drugs to consider for longevity based on my risk reward calculations.
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Wow - really good information. Thanks for posting this. Its great to have people here who have some in-depth experience with some of these compounds and biochemistry.
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