731 replies to this topic

[PWAIN]

Dasatinib is looking very promising together with Quercetin as a senolytic. It is used to kill senescent cells which is believed to significantly increase health span.

 

I have been in contact with Nyles. If you are interested in getting some Dasatinib then please either post here or contact me with pm. Better to get in quick because I don't want this to drag out. This is supposed to be 99% pure. Once I have a few more interested, I will pass the info to Nyles. Please don't contact Nyles directly just yet, I would like to keep this orderly for him. You will ultimately be dealing with Nyles directly, not me, I'm just trying to co-ordinate it.

PLEASE NOTE: This is for testing on your rat only!! All communication with Nyles should only indicate unambiguously that this is for your pet rat.

[niner]

Thanks, PWAIN.  Any idea of the price?  There are pharmaceutical versions on the net for ~80 USD/70mg pill.  US wholesale average is 367 USD/dose.  We would need to figure out how much to take, presumably converting from the mouse dose.  We should also take into account the fact that mice were dose i.p.

[Decimus]

Any idea what country it will be sourced from? If it is a reliable source, I am in for 4 pills. Thanks.

[Geoffrey1]

definitely interested--- will await details re price and how to proceed

thanks

Geoffrey

[ClarkSims]

http://www.cancercur...ount-Price.aspx

 

for 70 mg tablets

60 tablets USD 5091 USD 84.85

 

[Logic]

... We would need to figure out how much to take, presumably converting from the mouse dose.  We should also take into account the fact that mice were dose i.p.

 

No it was'nt!  

 

From the study:

"...A single dose of D+Q (D: 5 mg/kg body weight and Q: 50 mg/kg by oral gavage
here and in the following studies)..."
(Mice)
http://onlinelibrary.../acel.12344/pdf

 

HED (mg/kg) = Animal Dose (mg/kg) x [Animal Km / Human Km]*
Human Km = 37
Mouse Km = 3
Rat Km = 6
http://www.longecity...nimal-to-human/

 

So
HED for D is:  0.4054054054054054 mg/kg = 28.4mg/70kg human
HED for Q is:  4.054054054054054 mg/kg = 283.8 mg/70kg human

 

(I am ~ 110kg = 44.6 mg D & 445.9 mg Q)

 

Unless there are other factors to consider?

Differences in bioavailability between mice and humans?

Edited by Logic, 05 April 2015 - 09:58 PM.

[niner]

 

... We would need to figure out how much to take, presumably converting from the mouse dose.  We should also take into account the fact that mice were dose i.p.

 

No it was'nt!  

 

From the study:

"...A single dose of D+Q (D: 5 mg/kg body weight and Q: 50 mg/kg by oral gavage
here and in the following studies)..." [...]

 

HED for D is:  0.4054054054054054 mg/kg = 28.4mg/70kg human
HED for Q is:  4.054054054054054 mg/kg = 283.8 mg/70kg human

 

(I am ~ 110kg = 44.6 mg D & 445.9 mg Q)

 

Unless there are other factors to consider?

Differences in bioavailability between mice and humans?

 

Thanks for catching that, Logic.  I must have been thinking about another paper.  It's great that they used oral dosing; that's one less variable.  The HED for Dasatinib is probably safe, but I worry about the bioavailability of quercetin in humans relative to rodents.  It would be nice to know the concentrations that are considered necessary for quercetin to have an effect on the pro-survival pathways.  It would also be nice to know if you needed the aglycone, or if a glucuronidated version would work.  My inclination at this point would be to use the HED for Dasatinib, or maybe just go ahead and use a typical therapeutic dose like 70 mg, but take a lot more quercetin, like multiple grams, because of its poor bioavailabilty, and because it's well tolerated in most people.

[Logic]

A pleasure, Niner  

Have you looked at the graphs in the study? (figure 2 at the bottom)
I worry that too high a dose of Q could kill off proliferating cells?

 

[niner]

Have you looked at the graphs in the study? (figure 2 at the bottom)
I worry that too high a dose of Q could kill off proliferating cells?

 

In the quercetin-only plots, quercetin was pretty clean up to 10 uM, but showed some fall-off in proliferating cells after that.  I wouldn't worry at all about this, since we'd never even see 10 uM in vivo.  We'd have a hard time reaching 5, assuming that the aglycone is the active agent.  If a glycoside or glucuronide were active, that would change the equation.

[Logic]

In the quercetin-only plots, quercetin was pretty clean up to 10 uM, but showed some fall-off in proliferating cells after that.  I wouldn't worry at all about this, since we'd never even see 10 uM in vivo.  We'd have a hard time reaching 5, assuming that the aglycone is the active agent.  If a glycoside or glucuronide were active, that would change the equation.

Thx

So we don't know if its the aglycone, glycoside or glucuronide which is active?

[forn eldur]

I finally made an account because of this thread. I'm very interested in getting in on this.

[Logic]

I finally made an account because of this thread. I'm very interested in getting in on this.

 

The price quoted here is high.
TLR is doing 100x 30mg D & 300mg Q for $99 IIRC.
They aren't popular atm due to a group buy that is taking much longer than expected...

[forn eldur]

I saw that on their page just yesterday. I had good luck with their NSI-189. I wouldn't mind having to wait a few months for this one as I imagine it will make you quite sick before the results come and planning around vacation time will probably be a good idea. I just want to be sure that I'm getting real dasatinib. I suppose there is even a concern about real quercetin on today's market.

[Kalliste]

Quercetin is harmless enough that you can megadose several times using different brands to avoid being cheap-skated.

[PWAIN]

Bit of a catch up.

 

Niner, I believe $120 with 1 gram minimum.

 

Decimus, I'm not sure of the source country but I think t is in the US, you can confirm with Nyles.

 

Logic, no problem, might be a better deal, not sure. Just know that Nyles is pretty reliable so personally I feel more comfortable getting from him.

 

If anyone is interested in being part of a buy, please contact Nyles directly.

 

I look forward to seeing peoples reports on how their rat experiments went.

 

[ClarkSims]

To increse bioavailability one could just disolve it in dmso / water solution.  According to this thread it is 30mg/ml solubiliy in DMSO. 30 mg/ml in DMSO  30 mg/ml in DMSO

 

http://www.researchg...etin_solubility

 

One could apply it topically or sublingually, or drink it.

 

Alternatively, if one emullsified it with a heavy fatty acid it would bypass the liver and go into the lymph system. Perhaps emulsifying it with olive oil and lecithin? http://www.ncbi.nlm....pubmed/11879062

[njurkovi]

I would be interested if not too late

[Kalliste]

Is he still selling it? Does anyone know any other source?

[Logic]

Is he still selling it? Does anyone know any other source?

 

https://teamtlr.com/...&submit_search=

[mikey]

So, what have rats experienced?

[niner]

So, what have rats experienced?

 

Check out this very informative report from Fafner55.

[Wilberforce]

 

So, what have rats experienced?

 

Check out this very informative report from Fafner55.

 

This is extremely interesting.  Are there any other first hand reports, I've been looking?

[Logic]

Dasatinib group buy?

 

I am currently busy with the 3rd, very successful, buy of Nilotinib and would like to get myself some Dasatinib, which they also stock.

It could easily be added to the same parcel.

I can get 99% pure Dasatinib for , $ 2310.00 for 500g from the Nilotinib supplier.  )
That's $ 4.62 per gram, untested.

3rd party testing will add $ 600.00 to the price, bringing it up to $ 2910.00 for 500 grams.
That's $ 5.82 per gram, tested.
Postage via USPS Priority Mail Small Flat Rate Box differs depending on where you are in the world.  Its $ 6.80 in the USA.

I have not searched to see what people are paying for Dasatinib, so have no idea how this price compares?
I do know that there is 95% pure D available at a much lower price..?

If anyone is interested; please post the # of grams you would like, tested or untested, here:

http://www.longecity...ndpost&p=783944

[niner]

That's a fantastic price, Logic.  I'm in for ten grams.

[Logic]

That's a fantastic price, Logic.  I'm in for ten grams.

 

Great Niner.

So its yourself and SearchingForAnswers so far.

http://www.longecity...ndpost&p=784060

We're still way off the 500 gram minimum though!  

I'll do a new thread for the buy. (and post the link here)

Hopefully that will get some interest going.

 

What are your thoughts on liposomal or micellized quercetin?

I know we want to improve bioavailability and get the aglycone metabolite of Quercetin IIRC.

 

A Review of Quercetin: Chemistry, Antioxidant Properties, and Bioavailability

2009

http://www.jyi.org/i...ioavailability/

 

2011

Its absorption and metabolism (as well as its molecular targets) have been extensively explored from the viewpoint of its potential for disease prevention. It is known that glucuronide and/or sulfate conjugates with or without O-methylation exclusively circulate in the human bloodstream after intake of a quercetin-containing diet. We propose that glucuronide conjugates of quercetin function not only as detoxified metabolites but hydrophilic bioactive agents to various ROS-generating systems and precursors of hydrophobic aglycone. Quercetin aglycone is assumed to emerge in the target site by the action of β-glucuronidase activity under oxidative stress such as inflammation. The cardiovascular system and central nervous system seem to be the major targets of conjugated quercetin glucuronides circulating in the human bloodstream.

http://www.ncbi.nlm....pubmed/21773581

[Logic]

SearchingForAnswers is in for 40 grams..?

Niner                                           10

Logic                                           10

Total                                            60

 

Only 440 to go!  

[Logic]

SearchingForAnswers is in for 40 grams..?
Niner                                           10
Logic                                           10

Fafner55                                     10
Total                                            70

430 grams to go! 

Edited by Logic, 30 July 2016 - 10:18 PM.

[mikey]

I will buy 5 grams.

[SearchingForAnswers]

OK,

I'm working in Iraq and I have crappy bandwidth and work 72+ hour weeks. So I have not had time to catch up with the thread, and if all I need is 300 mg every 3 - 6 months, then obviously I don't need so much.

 

So put me in form 6 grams, I'd like to try this for awhile.

 

My assumption was that you took it everyday when you take your quercetin. Apparently not...

[Kalliste]

5 grams would be no problem. Is it powder or caps?

Assuming this is done with QC, will you provide the report on an external webpage for us to confirm or do we have to take your word for it?