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Is this the 4-HPR preclinical which you looked at?Nuclear...

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27/04/21

04:38

Post #: 52736546
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Originally posted by Mason14: ↑

Looks like a very interesting venture. Only looked at a review article for 4-HPR and the preclinical study evaluating 4-HPR.

Key points:
- unmet viral clinical need
- historic safety and efficacy data
- relatively low IC-50 value
- in vivo clinical efficacy for dengue fever in AG129 mice
- dosing in vivo comparable to historic dosing used in human trials

The table below summarises some of the studies that have evaluated 4-HPR. Notably, the bottom study used a more sophisticated packaging and achieved much higher plasma concentrations and fairly good response rate (1).

4-HPR treatment was similar in vitro to the previously researched nucleoside analogue NITD008. Unfortunately, due to toxicities, NITD008 was not an appropriate drug for dengue. Data supports the contention that 4-HPR acts at the RNA replication stage of infection, which I am assuming limits the production of proteins (2).

Response to treatment in vivo appears to increase as dose increases - twice daily dose improved survival better than a once daily dose. Curious as to whether a larger dose could provide greater efficacy. A 20 mg/kg dose in mice translates to a 60 mg/m2 dose in humans, which is much lower than the doses recorded above (2).

If I had some spare cash, I would be in this one. Will do some further reading and if anything comes up, I'll post it.

1 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5478002/pdf/10.1177_1535370217706952.pdf
2 https://pubmed.ncbi.nlm.nih.gov/24903662/

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Is this the 4-HPR preclinical which you looked at?

Nuclear Transport Inhibitor That Modulates the Unfolded Protein Response and Provides In Vivo Protection Against Lethal Dengue virus Infection

Johanna E. Fraser, Satoru Watanabe, Chunxiao Wang, Wing Ki Kitti Chan, Belinda Maher, Adam Lopez-Denman, Caroline Hick, Kylie M. Wagstaff, Jason M. Mackenzie, Patrick M. Sexton ... Show more

The Journal of Infectious Diseases, Volume 210, Issue 11, 1 December 2014, Pages 1780–1791,

https://academic.oup.com/jid/article/210/11/1780/2908496

========================

The article is dated 2014.
So it's taken seven years for not much to happen.
At least P1 can be skipped.

ILA Price at posting: 47.0¢ Sentiment: Buy Disclosure: Held
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