Drug-like Properties and Fraction Lipophilicity Index as a combined metric
Autor: | Anna Tsantili-Kakoulidou, Vassilis J. Demopoulos |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
Drug
Index (economics) media_common.quotation_subject fungi Medicine (miscellaneous) RM1-950 Combinatorics Drug likeness Chemistry (miscellaneous) Metric (mathematics) Lipophilicity Lipinski's rule of five Pharmacology (medical) Fraction (mathematics) drug-likeness oral drugs Fraction Lipophilicity Index Rule of 5 Molecular weight Polar atoms Therapeutics. Pharmacology General Pharmacology Toxicology and Pharmaceutics Mathematics media_common |
Zdroj: | ADMET and DMPK, Vol 9, Iss 3 (2021) ADMET and DMPK Volume 9 Issue 3 |
ISSN: | 1848-7718 |
Popis: | Fraction Lipophicity Index (FLI) has been developed as a composite drug-like metric combining logP and logD in a weighted manner. In the present study an extended data set confirmed the previously established drug-like FLI range 0-8 using two calculation systems for logP /logD assessment, the freeware MedChem Designer and ClogP. The dataset was split into two classes according to percentage of fraction absorbed (%FA) - class 1 including drugs with high to medium absorption levels and class 2 including poorly absorbed drugs. The FLI and FLI© (ClogP based FLI) drug-like range covers 93% and 90 % of class 1 drugs, respectively. The dependence of the degree of ionization to intrinsic lipophilicity within the FLI (FLI©) drug-like range as well as the inter-relation between the other Ro5 properties (Mw, HD, HA) was explored, so as to define drug-like / non drug-like combinations as a safer alternative to single properties for drug candidates’ prioritization. In this sense we propose a combined metric of Mw and number of polar atoms (Mw/NO) to account for both size and polarity. Setting the value 50 as cut off, a distinct differentiation between class 1 and class 2 drugs was obtained with Mw/NO>50 for more than 70% of class 1 drugs, while the opposite was observed for class 2 drugs. |
Databáze: | OpenAIRE |
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