- Reaction score
- 3,025
I've been trying to compare various data to help with sorting out darolutamide's equivalent strength to RU58841, and for anyone else interested in the theory I will post that data here.
Inhibition strength is determined by the IC50 data, which represents the concentration of a given anti-androgen required to block 50% of the androgen receptors present in the solution. The stronger the anti-androgen, the lower the IC50 data.
The difficulty with this is IC50 can be calculated many different ways (based on different chemical techniques), so it is only useful to compare when you have an "apples to apples" comparison in the same study. Comparing the raw numbers is not useful if they come from different studies.
So I have gone through the studies that exist comparing anti-androgens, and tried to use their data to work out rough conversions.
If you're not into chemistry, just skip to the bottom.
RAW DATA
1) Darolutamide vs. Enzalutamide vs, Apalutamide:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4490394/
- Darolutamide = 26 nm
- Darolutamide's major metabolite ORM-15341 = 38 nM
- Enzalutamide = 219 nM
- Apalutamide = 200 nM
Therefore, for 50% inhibition, enzalutamide requires 8.4x more concentration as darolutamide.
2) RU58841 vs. Hydroxyflutamide:
https://www.researchgate.net/profil...in-the-Bald-Scalp-of-Stumptailed-Macaques.pdf
- RU58841 = 100 nM
- Hydroxyflutamide =~ 100 nM (states as "similar")
Therefore, for 50% inhibition, RU58841 and hydroxyflutamide require approximately the same concentrations.
3) Bicalutamide vs. Hydroxyflutamide:
https://www.nature.com/pcan/journal/v1/n6/abs/4500262a.html
- Bicalutamide = 100 nM
- Hydroxyflutamide = 300 nM
Therefore, for 50% inhibition, hydroxyflutamide requires 3x the concentration of bicalutamide. This may be controversial as other studies have found these two to be closer to 1:1. ref
4) Enzalutamide vs. Bicalutamide
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2981508/
Enzalutamide = 21.4
Bicalutamide = 160 nM
Therefore, for 50% inhibition, bicalutamide requires 7.4x the concentration of enzalutamide.
DAROLUTAMIDE vs. RU58841
Based on this we can approximate that darolutamide is 8.4x more potent than enzalutamide, which is in turn 7.4x more potent than bicalutamide, which is in turn between 1-3x more potent than RU58841.
Therefore, darolutamide is likely approximately 62.16-186.5x more potent than RU58841.
Equivalent % of darolutamide to 5% RU58841:
RU58841 molar mass = 369.3 g/mol
Darolutamide molar mass = 398.8 g/mol
5% RU58841 = 100 mg RU / 2 mL solvent = 0.135 mM
Equivalent darolutamide concentration range = 0.0007239 mM to 0.00217 mM = 0.0289% to 0.0865%
Therefore, RU58841 5% is roughly equivalent to darolutamide 0.029-0.087%.
Inhibition strength is determined by the IC50 data, which represents the concentration of a given anti-androgen required to block 50% of the androgen receptors present in the solution. The stronger the anti-androgen, the lower the IC50 data.
The difficulty with this is IC50 can be calculated many different ways (based on different chemical techniques), so it is only useful to compare when you have an "apples to apples" comparison in the same study. Comparing the raw numbers is not useful if they come from different studies.
So I have gone through the studies that exist comparing anti-androgens, and tried to use their data to work out rough conversions.
If you're not into chemistry, just skip to the bottom.
RAW DATA
1) Darolutamide vs. Enzalutamide vs, Apalutamide:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4490394/
- Darolutamide = 26 nm
- Darolutamide's major metabolite ORM-15341 = 38 nM
- Enzalutamide = 219 nM
- Apalutamide = 200 nM
Therefore, for 50% inhibition, enzalutamide requires 8.4x more concentration as darolutamide.
2) RU58841 vs. Hydroxyflutamide:
https://www.researchgate.net/profil...in-the-Bald-Scalp-of-Stumptailed-Macaques.pdf
- RU58841 = 100 nM
- Hydroxyflutamide =~ 100 nM (states as "similar")
Therefore, for 50% inhibition, RU58841 and hydroxyflutamide require approximately the same concentrations.
3) Bicalutamide vs. Hydroxyflutamide:
https://www.nature.com/pcan/journal/v1/n6/abs/4500262a.html
- Bicalutamide = 100 nM
- Hydroxyflutamide = 300 nM
Therefore, for 50% inhibition, hydroxyflutamide requires 3x the concentration of bicalutamide. This may be controversial as other studies have found these two to be closer to 1:1. ref
4) Enzalutamide vs. Bicalutamide
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2981508/
Enzalutamide = 21.4
Bicalutamide = 160 nM
Therefore, for 50% inhibition, bicalutamide requires 7.4x the concentration of enzalutamide.
DAROLUTAMIDE vs. RU58841
Based on this we can approximate that darolutamide is 8.4x more potent than enzalutamide, which is in turn 7.4x more potent than bicalutamide, which is in turn between 1-3x more potent than RU58841.
Therefore, darolutamide is likely approximately 62.16-186.5x more potent than RU58841.
Equivalent % of darolutamide to 5% RU58841:
RU58841 molar mass = 369.3 g/mol
Darolutamide molar mass = 398.8 g/mol
5% RU58841 = 100 mg RU / 2 mL solvent = 0.135 mM
Equivalent darolutamide concentration range = 0.0007239 mM to 0.00217 mM = 0.0289% to 0.0865%
Therefore, RU58841 5% is roughly equivalent to darolutamide 0.029-0.087%.
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