"Being a small molecule blocker like maraviroc it
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Posted On: 10/20/2020 12:08:08 AM
"Being a small molecule blocker like maraviroc it might be causing liver issues."
Was going to ask why would maraviroc and other small molecule CCR5 inhibitors possibly cause liver issues, but leronlimab wouldn't? Having gotten no answer, I decided to look again some more and found only that maraviroc is metabolized in the liver by P450 / CYP3A.
A discussion when CCR5 antagonists were first in development about possible class effect of small molecule inhibitors having liver toxicity:
https://www.natap.org/2005/EACS/eacs_5.htm
I'm guessing nobody knows why, and Abbvie is just being very cautious with the potential liver toxicity issue. They too are doing trials of cenicriviroc for NASH. Blocking CCR2 and CCR5 may lead to better anti-inflammatory and anti-fibrotic activity, but have to see what the trials show.
Was going to ask why would maraviroc and other small molecule CCR5 inhibitors possibly cause liver issues, but leronlimab wouldn't? Having gotten no answer, I decided to look again some more and found only that maraviroc is metabolized in the liver by P450 / CYP3A.
A discussion when CCR5 antagonists were first in development about possible class effect of small molecule inhibitors having liver toxicity:
https://www.natap.org/2005/EACS/eacs_5.htm
I'm guessing nobody knows why, and Abbvie is just being very cautious with the potential liver toxicity issue. They too are doing trials of cenicriviroc for NASH. Blocking CCR2 and CCR5 may lead to better anti-inflammatory and anti-fibrotic activity, but have to see what the trials show.
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