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.
http://www.sciencedirect.com/science/article/pii/S1359644615003505

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.

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Published by iwatobipen

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

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