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Author Topic: Navitoclax (ABT-263) induces apoptosis of fibroblasts  (Read 2179 times)

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AlmostBlue

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Navitoclax (ABT-263) induces apoptosis of fibroblasts
« on: March 11, 2018, 01:10:24 AM »

https://www.ncbi.nlm.nih.gov/pubmed/29237758

https://medicalxpress.com/news/2017-12-drug-apoptosis-myofibroblasts-fibrosis-scleroderma.html

Pushing cells to self-destruct combats deadly fibrosis | Science | AAAS

https://sclerodermanews.com/2018/01/11/cellular-self-destruction-trigger-explored-as-scleroderma-treatment/

Very interesting stuff. There are a few other articles out there. You guys can search something like "navitoclax fibrosis" and check them out. I am surprised this hasn't been posted yet.

This is very similar to the discovery of the anti-CD47 antibody and its ability to reverse fibrosis. There is already a thread on that in this section. Both new, non-FDA approved anti-cancer treatments work in a nearly identical way when it comes to eliminating fibrosis.

If you do a google search, Navitoclax can be bought online from chem suppliers it looks like. In the anti-cancer trials they did 120mg per day, if I remember reading correctly. It was well tolerated and the main side effects were dizziness, nasuea, etc. The possible side effect that caused alarm was that this drug can reduce the # of platelets with high doses.

Would trying a dose like 40 or 50mg per day for something like 5 days be a bad idea? I am pretty desperate at this point and I wonder if this could be a real fix. I have no intentions of that and I am not advocating for anyone to try, I would just like to spark conversation.

Between Navitoclax, the anti-cd47 antibody, that E4 peptide, I am a tad on the optimistic side for ridding ourselves of this horrible disease. These 3 drugs seem to be ways for the body to reverse/get rid of the fibrosis altogether. Additionally, i am optimistic for mediwound's mwpc003.
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Paolo

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Re: Navitoclax (ABT-263) induces apoptosis of fibroblasts
« Reply #1 on: March 11, 2018, 04:21:13 AM »

AlmostBlue, this is your first posting, to avoid conflict of interest can we have your story, do you have peyronie's ??? ???

If you want to 'spark conversation' let's have 'your' story please  :)
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skunkworks

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Re: Navitoclax (ABT-263) induces apoptosis of fibroblasts
« Reply #2 on: March 11, 2018, 08:36:30 AM »

Had not heard of navitoclax, thanks for the heads up. It certainly does seem like it could be interesting with regards to Peyronie's, but I doubt it will be safely available for quite some time. Definitely not playing Russian roulette with black market suppliers.

Crooked_Stick

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Re: Navitoclax (ABT-263) induces apoptosis of fibroblasts
« Reply #3 on: March 11, 2018, 10:59:47 AM »

Good post almostblue, I believe there will be a cure for Peyronies Disease...as I’ve stated before, MWPC003 has huge promise....itis the same enzyme used in Mediwound’s Nexibrid ans Escharex which are in phase II and III....they are waiting to get their first two products to market before proceeding with the injectable version that will be used for connective tissue disorders including Peyronies Disease.....I believe that MWPC003 could be used to dissolve the plaque followed by a stem cell treatment to grow blood vessels and nerves
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pey ron

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Re: Navitoclax (ABT-263) induces apoptosis of fibroblasts
« Reply #4 on: March 13, 2018, 03:50:13 PM »

@AlmostBlue: can you please send me a PM (private message) with all the websites where you have found this drug so far?

To send me a PM, just click on the symbol under my name to the left of this reply.

thank you!
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hope794

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Re: Navitoclax (ABT-263) induces apoptosis of fibroblasts
« Reply #5 on: June 03, 2018, 04:57:31 PM »

Anyone got news about this? Are they going to open trials?
If anyone knows something, please share.
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24 yo from Italy.Peyronie's probably since 2014.Since then,penis bends of about 10-15°, with a slight twist to the left.Moderate Erectile Dysfunction since 2 years and things getting worse.From pornstar-like to moderately depressed,but still fighting for a solution.

Werther

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Re: Navitoclax (ABT-263) induces apoptosis of fibroblasts
« Reply #6 on: December 03, 2018, 11:27:43 AM »

Is there any way to purchase this? It looks like it's been around for quite some time so far (e.g. ABT-263: A Potent and Orally Bioavailable Bcl-2 Family Inhibitor | Cancer Research).

Can a doctor prescribe it? Maybe an oncologist?
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Cacogen

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Re: Navitoclax (ABT-263) induces apoptosis of fibroblasts
« Reply #7 on: December 19, 2018, 01:27:19 AM »

Do we even know what specific anti-apoptotic proteins need to be targeted in Peyronie's myofibroblasts? Navitoclax might not block them, or not block them all. If this were likely to work well on all types of pathological fibrosis, I would think there would be papers out already studying efficacy in rodent models of idiopathic pulmonary fibrosis -- which is of course quite deadly.

Tempting though it may be, I'm not sure I would self-experiment -- Bcl-XL inhibition can cause thrombocytopenia:

Because navitoclax inhibits Bcl-XL, it reduces platelet lifespan, causing thrombocytopenia, and this makes it dose-limiting.

https://en.wikipedia.org/wiki/Navitoclax#Mechanism_of_action

You would want to make sure you got dosages right, and I'm not sure it's clear what the correct dosage would be, because this was a rodent study, right?

Interestingly, navitoclax also appears to be a senolytic agent, selectively destroying senescent cells -- just in case senescence plays some role in Peyronie's pathology.

Inducing myofibroblast apoptosis does sound extremely promising. It might even cure Peyronie's -- or perhaps stop and reverse a significant amount of the fibrosis (possibly Peyronie's-deposited ECM proteins are harder to reverse than those from scleroderma?). 
 
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Werther

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Re: Navitoclax (ABT-263) induces apoptosis of fibroblasts
« Reply #8 on: August 19, 2019, 07:49:15 PM »

I personally don't know if anything's being done with regards to this whole subject but it looks like some other steps were made further from the researchers working on this molecule.

Here is what I found: this is the first study to demonstrate that PF can be reversed by a senolytic drug such as ABT-263 after it becomes a progressive disease. Therefore, ABT-263 has the potential to be developed as a new treatment for PF (full text: https://www.ncbi.nlm.nih.gov/pubmed/28479002).

Then,you can see that, within the same year, it was reported that "Using a BH3 profiling assay to assess mitochondrial priming in dermal fibroblasts derived from patients with scleroderma, we demonstrate that the extent of apoptosis induced by BH3 mimetic drugs correlates with the extent of their mitochondrial priming, indicating that BH3 profiling could predict apoptotic responses of fibroblasts to BH3 mimetic drugs in patients with scleroderma. Together, our findings elucidate the potential efficacy of targeting myofibroblast antiapoptotic proteins with BH3 mimetic drugs in scleroderma and other fibrotic diseases (full text: https://www.ncbi.nlm.nih.gov/pubmed/29237758).

Now, having passed two years from the abovementioned papers, do you think that maybe any of us should get in contact with the  authours of these studies in order to ask them - at the very least - if peyronie's fibrosis  applyes to the mechanims of action of this drug and if their reply would be confirmative - as I hope - some of us could maybe get enrolled in their trial and then report to the forum!

What do you all think about this?
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hope794

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Re: Navitoclax (ABT-263) induces apoptosis of fibroblasts
« Reply #9 on: August 23, 2019, 02:50:34 PM »

Great question Werther! Is someone willing to do what Werther said?
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24 yo from Italy.Peyronie's probably since 2014.Since then,penis bends of about 10-15°, with a slight twist to the left.Moderate Erectile Dysfunction since 2 years and things getting worse.From pornstar-like to moderately depressed,but still fighting for a solution.

pey ron

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Re: Navitoclax (ABT-263) induces apoptosis of fibroblasts
« Reply #10 on: August 24, 2019, 04:18:56 AM »

While we find a way to get navitoclax or dasatinib, natural products with similar activities:

https://docdro.id/HtLwzZB
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hope794

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Re: Navitoclax (ABT-263) induces apoptosis of fibroblasts
« Reply #11 on: August 24, 2019, 07:41:31 AM »

Thanks for the infos, pey ron.
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24 yo from Italy.Peyronie's probably since 2014.Since then,penis bends of about 10-15°, with a slight twist to the left.Moderate Erectile Dysfunction since 2 years and things getting worse.From pornstar-like to moderately depressed,but still fighting for a solution.

Werther

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Re: Navitoclax (ABT-263) induces apoptosis of fibroblasts
« Reply #12 on: August 24, 2019, 01:00:34 PM »

Just one question that, apparently, was missed by everybody: is this drug actually marketed?

Put in layman's terms, can you actually buy this from the producer a franchisee or any other legitimate source or is there only the dark web (and its associated risks) for this?

I hope that anyobody with some knowledge on the subject can chime in and give helpful information. It would be helpful for everybody and it would be very appreciated.
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pey ron

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Re: Navitoclax (ABT-263) induces apoptosis of fibroblasts
« Reply #13 on: August 24, 2019, 01:11:03 PM »

If enough of us are willing to experiment, we could do a group-buy from a chemical supplier. I have contacts that have run mass-spectrometry tests and looked for solvent residuals several times before. But first we would need a good number of pioneers to achieve economy of scale.
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Patientxyz1992

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Re: Navitoclax (ABT-263) induces apoptosis of fibroblasts
« Reply #14 on: August 24, 2019, 01:43:56 PM »

This looks very promising, i posted multiple times in development drugs section about some researches about other possible treatmants like dickpof and ab007 but i dont know why they pop out with this researches and after that zero, nada , it looks like there is multiple promising treatmants for peyronie disease but in my opinion the cure will come secundary to primary cure fore other conditions like lung fibrosis etc... it really sucks because i seen dozens of potentional cures and thats it ,no further research....so i dont know what we can do to change that?
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Werther

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Re: Navitoclax (ABT-263) induces apoptosis of fibroblasts
« Reply #15 on: August 24, 2019, 06:18:06 PM »

If enough of us are willing to experiment, we could do a group-buy from a chemical supplier.

I agree with you but IMO this would only be really useful for drugs that are currently out of the market (nobody is producing them and they are not being sold anywhere).

Navitoclax however has been around for at least a decade (it has been tested on a clinical trial in 2009) so I don't know how worth is the risk experimenting with a synthesized compound supposedly similar to it when you could actually get your hands on the real thing. The same goes for other drugs out of there that sound promising.

That's why I was asking the above. I hope there's anyone who have info and can reach out. Send me a PM in case.
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pey ron

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Re: Navitoclax (ABT-263) induces apoptosis of fibroblasts
« Reply #16 on: August 25, 2019, 02:00:03 AM »

how can we actually get our hands on it? no doctor will prescribe it off-label because they will all be afraid of liabilities :(
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Werther

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Re: Navitoclax (ABT-263) induces apoptosis of fibroblasts
« Reply #17 on: August 25, 2019, 09:56:18 AM »

You are right but the same goes for other drugs that might be potentially useful but have never been experimented with regards to peyronie's. I'm thinking of metformin as an example: nobody (I'm talking about the medical community) ever tested it for peyronie's so you would never get an urologist to prescribe it for peyronie's but nonetheless there are ways to get it since it's on the market (e.g. you could trade it with diabetics or go as far as to falsify prescriptions in order to get it).

I think the same could be done for Navitoclax. Maybe a joint venture with scleroderma's patients could help...  ::)
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