Hello experts/colleagues!
I am currently designing a rat disease model experiment and need to screen a reliable myeloperoxidase (MPO) inhibitor for in vivo intervention. I have the following practical concerns:
Efficacy and species specificity:
Which MPO inhibitors have been verified for in vivo activity in rat models? For example, the inhibitory efficiency of classic drugs (such as ABAH, 4-ABAH) or new compounds on rat MPO enzymes (such as whether there is a public rat MPO-inhibitor binding IC50 data)? Is it necessary to pay special attention to the species differences between inhibitors and rat and human MPO?
Feasibility of administration:
For the commonly used administration routes of rats (such as oral or injection), which inhibitors have good bioavailability? For example, does the oral preparation need to consider solvent-assisted dissolution (such as whether DMSO/corn oil is required for poor water solubility), and are there any literature reports of solvent toxicity or injection site irritation for injectable inhibitors? Is there any reference data on the safe dosage range for long-term administration (such as 2-4 consecutive weeks)?
Selectivity and side effects:
Prioritize inhibitors with high selectivity for MPO (avoiding significant inhibition of other peroxidases such as EPO or off-target effects). Are there any studies showing that some inhibitors are prone to cause liver and kidney dysfunction or other side effects in rats? For example, have thrombocytopenia, gastrointestinal reactions, etc. been observed that need to be avoided?
In combination with your needs for MPO inhibitors in rat experiments, based on existing literature data and compound characteristics, we recommend two research tool drugs for your reference:
1. AZD5904 (Cat.NO.: HY-111341)
AZD5904 has been verified to have a clear inhibitory effect in vivo in mouse tumor models (PMID: 36805920) and has shown good tolerability. However, no dosing literature directly targeting rat models has been retrieved.
If AZD5904 is selected as a potential candidate for rat experiments. It is recommended to design a preliminary experiment in advance, and convert the effective dose and dosing method reported in the literature for mice to rats according to body surface area, and simultaneously monitor MPO enzyme activity and safety indicators (such as blood routine, liver and kidney function).
Please refer to MCE for the calculation guide of equivalent doses for different animals:
https://file.medchemexpress.com/HandlingInstruction/Compound%20Handling%20Instructions.pdf
2. Verdiperstat (Cat.NO.: HY-17646)
The in vivo activity of Verdiperstat has been verified in the rat acute lung injury (ALI) model (PMID: 35461824), which can significantly reduce tissue MPO expression and improve pathological damage.
I hope the above information will be helpful for your experimental design! If you need more details or pre-experimental planning suggestions, please feel free to communicate!
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