Im not Castrate resistant but will eventually be so this is an important article in understanding and targeting resistance.
This is technical at first but if you work your way through it there are excellent data on why abiraterone, apilutamide, Enzalutimide fail, and how pretty awesome darolutamide is, but its not invincible.
Basically this article really delves into the N terminus, ligand binding and DNA binding domaines with excellent graphs. It also explains how the different AR Variants come about and how they progress and proliferate. Then the article shows present drugs some approved like niclosamide an anthilmentic fights the ARV-7 mutation, and a bunch of upcoming N-terminal domain inhibitors and other inhibitors.
So the future looks bright and for anyone that has failed Enz, apilutamide , abiraterone, even ( Darolutamide which I haven’t delved into that rabbit hole yet).
This article lists the new potential drugs and clinical trials.
Preclinical data show Niclosamide inhibits the expression of AR-V7 and lessens the resistance to LBD-targeting drugs in tumours with this variant, presumably by restoring the expression of full-length AR [96]. In fact, the combination of Enzalutamide and Niclosamide in Enzalutamide-resistant models allows for degradation of the constitutively active AR-V7, diminishing the concentration of AR protein without an LBD that Enzalutamide can bind to and inhibit and thus there is a higher percentage of full-length AR protein to be inhibited by Enzalutamide. A combination of this treatment showed inhibition of tumour cell growth and the induction of apoptosis, whilst also reducing recruitment of the AR to target gene promoter regions
Search for niclosamide in this forum. There are many posts and comments. The regular niclosamide does not work because is not well absorved in the gut. The clinical trial used a modify niclosamide which has a much better absorption. It is impossible to get outside the trial.
How do i get PURE 100% niclosamide?If you use DMSO everything has to be pure.
Do you know of a lab for pharmaceutical grade niclosamide?
Also one really has to be careful with dosing if your breaking new ground.
The other big problem with breaking new ground is testing and all us patients have for testing is the usual CMP, CBC, and other run of the mill labs that need to be prescribed if you don’t want to pay out of pocket
Looks legit. Still need to determine dosage if using it via dmso either topically or orally.Need to find completed clinical trials for dosing. At least completed phase 2.
I believe that even 100% pure niclosamide is not absorbed enough to reach a therapeutic level.
They used niclosamide/PDMX1001 in the trial. I tried to get this niclosamide and it was impossible. It is made by a biotech company in California and they do not want anybody using this compound outside a clinical trial. I would not experiment with niclosamide only, since the amount one has to take to get therapeutic level in the blood will cause intestinal problems.
All the information is on line. just check PUBMED for niclosamide and prostate cancer.
Thanks tango65, I searched for the modified niclosamide and here is a snipit on it for covid trials. On February 9, AzurRx entered into an agreement with the global contract research organization (CRO) PPD to oversee a planned Phase II clinical trial evaluating a proprietary formulation of micronized niclosamide as a treatment for COVID-19-associated gastrointestinal (GI) infections. PPD plans to manage the Phase II clinical trial for an immediate-release capsule formulation of micronized oral niclosamide.
So I wonder how they micronize it.
It is a small molecule anthilmentic.
Very interesting.
I was already thinking of starting up my fenbendazole (anthilmentic) with dmso infused with black walnut i made. I took this for 4 months as part of JTP and COC protocol. It didn’t work on stopping my cancer prior to going on ADT (lupron/darolutamide).
Im pretty confident lupron and darolutamide won’t terminate my cancer cells completely so adding an anthilmentic is fairly harmless except need to keep an eye on liver enzymes.
Did you stop fenben after four months? My PSA rose in months 3 and 4 after starting fenben, then began a long decline, hitting new lows a year later. Stable for the last 15 months. Not sure what is working, but you may want to give it a longer trial.
Hmmm, i was first doing fenben packets with fatty food for I forgot how long, then went to pure fenben with dmso, then went to Mebendazole via COC doctor.But i was running out of time as my psa kept climbing so I couldn’t take chance of mets going to bones. But now i can hit the cancer again with it now that it is stressed and presently under control
Just to clarify, I use fenben in addition to SOC treatment, not instead of. I was on Lupron 15 months before starting fenben, been on both (plus supplements, etc.) another 29 months. Lowest PSA was 0.5 in April 2021, now 0.66
I am still doing cbd which i grew and make my own RSO with it, I also do other sups, but i cut back on everything to bring my liver enzymes back to normal, they weren’t bad but were out of tolerance. So now I will slowly add things back in. No metformin or doxycycline as both cause intestinal issues. I was taking probiotics and eating prebiotic food but the metformin just caused to much stomach issues
I don't think it's really rising. I had one reading of 0.5 in 3.5+ years. On the other hand, I've had a number of 0.6 readings. And during the first two years (early 2019-2020), it bounced up and down from 0.7 to 1.4. So the last 19 months have been the most consistently low period since beginning Lupron. The period since beginning fenben has hit those consistent lows. Unless there's a trend upward, I don't know that a tenth is indication of a trend.
Here is a communication among chemists on reformulation of niclosamide to make it more bioavailable.
They made a statement in the communications
“However, NCL is classified according to the Biopharmaceutical Classification System as class II showing very limited oral bioavailability due to its poor solubility in water (5-8 mg/L)7,8. Consequently, its action is local in the intestine and does not reach suitable plasma levels for systemic therapeutic applications. Most of experiments showing in vitro activity are conducted by using DMSO solutions, which obviously cannot be used for systemic use in humans. Barbosa and collaborators (2019) reinforce that one of the biggest challenges for the use of niclosamide in systemic therapies (e.g. tumors or infections) is its low solubility in water, since its crystalline structure and high lipophilicity affect oral absorption9. ”
So the statement in middle of the above paragraph states”
Most of experiments showing in vitro activity are conducted by using DMSO solutions, which obviously cannot be used for systemic use in humans. “
So I know you can orally take DMSO but it needs to be cut after disolving fenbendazole init. Cut it with 50% distilled water : 50% pure DMSO
Niclosamide [N-(2′-chloro-4′-nitrophenyl)-5-chlorosalicylamide] (Figure 1) is an anthelmintic drug developed to treat tapeworm infections in early 1960 ́s1 and it is listed in the WHO list of essential medicines. Niclosamide has been evaluated in clinical studies for cancer treatment and, also several in vitro studies indicate that NCL has great potential to act as a broad-spectrum viral replication inhibitor, including major infections such as zika, hepatitis C, adenovirus, chikungunya, dengue, among others 2–5. Recently it has been identified as a potential candidate to treat SARS-CoV-2 infections5,6, which can be a solution in part to the ongoing pandemic. However, NCL is classified according to the Biopharmaceutical Classification System as class II showing very limited oral bioavailability due to its poor solubility in water (5-8 mg/L)7,8. Consequently, its action is local in the intestine and does not reach suitable plasma levels for systemic therapeutic applications. Most of experiments showing in vitro activity are conducted by using DMSO solutions, which obviously cannot be used for systemic use in humans. Barbosa and collaborators (2019) reinforce that one of the biggest challenges for the use of niclosamide in systemic therapies (e.g. tumors or infections) is its low solubility in water, since its crystalline structure and high lipophilicity affect oral absorption9. Thus, these undesirable characteristics can compromise its clinical efficacy, since they result in the need for administration of high doses to patients, which causes unwanted adverse effects such as, for example, colitis, diarrhea and gastrointestinal irritation, in addition to not reaching levels plasma levels for the desired therapeutic activity.
Some alternatives have been reported to advance in the state of the art and improve the solubility of niclosamide; however, the majority have clear limitations for the production of tablets and capsules for mass administration, due to the great challenge that this drug represents. In the present communication, we report the result of the screening of orally approved pharmaceutical polymers to form a relatively stable amorphous solid dispersion, which shows potential use in the reformulation of this drug in solid dosage forms aiming to improve its solubility and, consequently, its oral bioavailability.
Adverse events observed in patients on treatment are summarized in Table 2. No dose-limiting toxicities were observed during the first cycle of treatment at each dose level up to dose level 3 (DL3) with PDMX1001/niclosamide at 1200 mg po tid, abiraterone 1000 mg po qd and prednisone 5 mg po bid. Dose Level 4 (PDMX1001/niclosamide 1600 mg po tid) intra-patient escalation was considered optional as niclosamide levels already reached therapeutic concentration in plasma as shown below. Nevertheless, almost all patients were able to reach DL4. The combination of abiraterone acetate, prednisone, and niclosamide was well-tolerated, with few Grade 3 toxicities
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