2020年7月16日木曜日

2020-2021 Protocol for Clinical trials of "15K",
1,2,3-triazolyl ester of ketorolac, against COVID-19, compared with Ivermectin as the positive control.


The above article of ours on “PAK1-blockers: Potential therapeutics against COVID-19” has been cited over 800 times during last 3 months since its publication in mid-April 2020, this “working hypothesis” of ours appears to be widely accepted or seriously considered among world medical/ scientific community.
Considering the current “gloomy” situation that  the COVID-19 pandemic, costing nearly 600,000 deaths during last 6 months, is still actively hanging around world-wide, in particular US, and it will take 6-12 more months till any effective vaccine becomes available world-wide, we will try to contact a pharma, asking for making 200 g of 15K, our potent PAK1-blocker, at GMP facility for its clinical trials against COVID-19, with at least 100 patients for 30 days, compared with Ivermectin (0.15 mg/kg once or twice) which has been proven to be effective clinically. For detail of the Ivermectin clinical trials against COVID-19, see below:
Once FDA approves 15K for marketing, we shall try to organize its clinical trials against chemo-resistant pancreatic cancers and many other PAK1-dependent diseases.  Sometimes we have to change a plan or strategy, depending on the given situation. Flexibility is the key for a great success.
The “clinical” protocol:
According to our own in vivo (pancreatic cancer xenografts in mice) test of 15K, its daily dose of 0.1 mg/kg is sufficient to suppress almost completely the growth of these cancers at least, and even 5 mg/kg (50 times of the EC) causes no side effect: 
Thus, the testing dose of 15K for COVID-19 patients treated at ICU (intensive care unit) would be around 0.1 mg/kg daily or less (6 mg/60 kg, twice a week). Thus, for the first round of trials, we need at least 20 g of 15K, around 6-7, 000 tablets of 3 mg, sufficient for treating at least 100 patients over 30 days. Since 15K is expected to lower the blood pressure to a certain extent, we shall monitor both their blood pressure and COVID-19 symptom closely during 15K treatment (up to 30 days, dead or alive). 

Of course, we shall ask more than a dozen "healthy" volunteers including myself for taking the precisely same dose of 15K over a month, making it sure that 15K causes no side effect on these "healthy" individuals in advance.  

The Protocol for 15K synthesis 
15K was synthesized from an old PAK1-blocking pain-killer called “Ketorolac” (R-form) via Click Chemistry (CC), which catalyzes the esterization of its COOH with 2-azido anisole in the presence of copper ion with a high yield. For detail, see the following website:
This CC boosts the cell-permeability (and thereby both anti-cancer and anti-PAK1 activities) of Ketorolac over 500 times, but without any loss of its water-solubility.

0 件のコメント:

コメントを投稿