Metrics for Drug likeness

There are some indexes about drug likeness.
Of course, I sometime use LE, LLE for lead optimization.
Recently QED is new metrics for estimation of drug likeness.
Which parameters do you like ?
I read following paper that reported Patrick Barton et. al.
It’s interesting for me.

The author proposed new index named “AEI” ADMET efficiency index.
AEI is defined following formula.
AEI = pActivity -|logP| / PSA x 100.

The key difference of AEI and LE is that AEI is considered not only lipophilicity but also polarity(PSA).

The concept based on 75/3 Rules.
I think the proposal is useful, Fig2 shows cleanly separate BCS class II/III compounds using logP and PSA.

The author proposed compound classification system using AEI and provided decision tree(Fig8) .

Compounds falling into class A have AEI>7 with an AEI ranging from 7 to 31 and a mean of 9.9. For this class the median daily dose is 25 mg with 93% of this class having a total daily dose of <300 mg. Compounds within the range 4 < AEI 300 mg. Class C compounds where AEI < 4 are the most concerning representing a relatively poor LLE and ADMET profile.

The tree helpful for chemist to understand the compound profile.
I’ll try to calculate AEI for inhouse dataset.


Published by iwatobipen

I'm medicinal chemist in mid size of pharmaceutical company. I love chemoinfo, cording, organic synthesis, my family.

Leave a Reply

Fill in your details below or click an icon to log in: Logo

You are commenting using your account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s

This site uses Akismet to reduce spam. Learn how your comment data is processed.

%d bloggers like this: