Replies to post #98171 on Anavex Life Sciences Corp (AVXL)

[Turner2017]

Amstocks, Would you say that 2-73 compared to all other Alzheimer's trials going on has the best chance at becoming SOC? I know that is a vague question but I would like to know your opinion on how 2-73 stacks up against the rest of the drugs and trials going on....(I believe there are 23 of them)

[jakebanner]

Good post. Agree with your analysis. That is why PK/PD data will be telling. Metabolism, absorption, distribution and excretion are key. Response will be appropriate to administration of 2-73. So far, so good; so far so good . . .

[Swan5995]

Bryostatin-1 has not been synthetically synthesized yet as far as I know. Most that read Neurotrope's Jan. 30 PR would assume a process has been found to synthesize this molecule. However, a careful read of the PR shows that this is not the case. It would have been a major breakthrough if it had been synthesized and would have been clearly stated. Only a licensing agreement was signed with a group attempting to synthesize bryostatin (if successful). A viable means of commercial production remains a fatal flaw for bryostatin.

Otherwise, excellent write up.

[F1ash]

"The next reason that I think bryostatin-1 probably does not have the same impact is because bryostatin-1 is a natural product that scientists/doctors noticed seemed to have a positive neurological impact. It was not created to have an impact on Alzheimer's disease. The impact it does have is an accident of nature just as the side effects are accidents of nature. "

(Emphasize in above is mine.)

Oh ya, you mean like penicillin? The drug that basically changed the world of medicine?

https://www.google.com/amp/io9.gizmodo.com/in-case-of-apocalypse-heres-how-to-make-penicillin-in-1110902296/amp


And some how starting with a base chemical used in industrial applications is "better and safer". I question the logic!

A2-73 base chemical......


"* Tetrahydrofuran should be handled as a CARCINOGEN--WITH EXTREME CAUTION."

"* Tetrahydrofuran may damage the liver and kidneys."

"* Tetrahydrofuran can cause headache, nausea and dizziness. Very high exposure can cause unconsciousness and death."

"* There is limited evidence that Tetrahydrofuran causes cancer in animals. It may cause cancer of the liver and kidneys"








I believe I have seen a few hats here hanging from remarks by the "Editor" of the following:


New Drugs from Marine Organisms in Alzheimer’s Disease


"Bry-1 is a potent modulator of PKC [49]. PKC comprises eight isoforms (conventional: a, ßI/ßII, ?; and novel: d, e, ?, ?) enclosing the regulatory C1 domains [49]. The rings of Bry-1 molecule, after binding to C1 domain, protrude forming a cap. Bry-1, although is a hydrophilic molecule, which binds strongly to PKC, with a potency similar to that of phorbol ester (a canonical hydrophobic ligand), causing PKC-a, ß and d down-regulation and no PKC-e and RasGRP3 (RAS guanyl releasing protein 3 (calcium and DAG-regulated)) induction [50,51]. In brief, Bry-1 awakens a fast short activation and self-phosphorylation of PKCs that consecutively induces PKCs membrane translocation with succeeding PKCs down-regulation. The down-regulation of PKC-d isozyme shows a distinctive biphasic pattern: at low concentrations—a down-regulation and at higher concentrations—a mechanism of protection [51]. This property contributes in making Bry-1 an attractive drug for pharmaceutical development.

Preclinical studies show that Bry-1 is able to:

(i) enhance spatial learning and long-term memory in rats, mice, rabbits and the nudibranch (Hermissenda) [52,53];

(ii) increase spinophilin (regulatory subunit of protein phosphatase-1 catalytic subunit highly enriched in dendritic spines) and synaptophysin (major synaptic vesicle protein p38), synaptic proteins levels causing synapses structural changes [52];


(iii) exert neuroprotective effects on AD transgenic mice [54];

(iv) improve memory (measured as reduction in latency to escape, after oral Bry-1) in APP/PS1 (mice containing human transgenes for both amyloid precursor protein (APP), bearing the Swedish KM670/671NL (rs63751263, rs63750445) mutation and PSEN1 containing an L166P mutation (rs63750265), both under the control of the Thy1 promoter) transgenic mouse [55];

(v) reduce Aß levels in monomeric Aß-treated cells “in vitro” [56];

(vi) reduce Aß levels in Tg2576 AD mouse (mice overexpressing a mutant form of APP (isoform 695)) and aged rat recovery [57];

(vii) recover neurotrophic activity and synapses loss [57];

(viii) prevent neuronal apoptosis [57];

(ix) inhibit t phosphorylation by GSK-3ß inhibition [57];

(x) enhance synaptogenesis, leading cognitive deficits recovery [57].


http://www.mdpi.com/1660-3397/14/1/5/pdf

Received: 5 November 2015; Accepted: 21 December 2015; Published: 25 December 2015 Academic Editor: George Perry


That name looks familiar, can't think of where I have seen it before?


More to come....

























Replies:
re. "That name looks familiar, can't think of
FooBarAndGrill on 3/29/2017 9:18:23 AM



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