Yes, leronlimab is competitive inhibition (blocks
Post# of 155523
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Posted On: 08/28/2019 4:21:58 AM
Yes, leronlimab is competitive inhibition (blocks the point hiv attaches) where as maraviroc is non-competitive or allosteric. The inhibition curve will look different, non-competitive plateau or level off at some point, where as competitive goes to 100% as the concentration is higher (see image below).
With Maraviroc,alters the geometry of CCR5, so the binding site is not recognized or is hidden, but the resistance strains within R5 work around this by changing their geometry to again match. Leronlimab still blocks these resistant R5 strains to Maraviroc
There are three main chemokines that interact with CCR5: CCL3/MIP-1-alpha, CCL4/MIP-1-beta and CCL5/RANTES. Leronlimab was selected from 16 or so possible compounds, the paper is linked here somewhere, to minimize interfering with these chemokine activity while still blocking HIV. It does still inhibit signaling, but at higher concentrations, though I believe RANTES is the main one. which has allowed leronlimab to work in the cancer setting. So this allows for a good safety profile. Where as Maraviroc blocks the activity much more giving terrible side-effects sometimes.
The exact IC50 values, etc, of leronlimab, I have listed the paper here somewhere, I would have to find it. But I remember posting this image in my image history from the paper.
With Maraviroc,alters the geometry of CCR5, so the binding site is not recognized or is hidden, but the resistance strains within R5 work around this by changing their geometry to again match. Leronlimab still blocks these resistant R5 strains to Maraviroc
There are three main chemokines that interact with CCR5: CCL3/MIP-1-alpha, CCL4/MIP-1-beta and CCL5/RANTES. Leronlimab was selected from 16 or so possible compounds, the paper is linked here somewhere, to minimize interfering with these chemokine activity while still blocking HIV. It does still inhibit signaling, but at higher concentrations, though I believe RANTES is the main one. which has allowed leronlimab to work in the cancer setting. So this allows for a good safety profile. Where as Maraviroc blocks the activity much more giving terrible side-effects sometimes.
The exact IC50 values, etc, of leronlimab, I have listed the paper here somewhere, I would have to find it. But I remember posting this image in my image history from the paper.
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