Abstract
Permeability is important in governing the ability of drug substances to transport across gastrointestinal membrane and also crucial for proper drug distribution to pharmacological target organs and cells, and is therefore frequently utilized in drug discovery and development. In this report, we have performed a systematic analysis, using principal component analysis on the historically measured permeability data from in-house Caco-2 and parallel artificial membrane permeability assays on discovery new chemical entities from multiple projects. This work allows for establishment of a permeability diagnosis model by purposefully identifying most influencing physicochemical properties of the permeability issues, including polarity-lipophilicity line contributed primarily by polar surface area and LogP, number of rotation bond, fractional ionization at neutral pH and efflux ratio. A number of cases were also shown to demonstrate the applicability of the current model. The analysis of the model over internal drug discovery compounds exhibited promising diagnostic and predictive power of the model. The advantages and limitation of the model as well as the integral strategy to apply it in drug discovery to guide projects for permeability-related optimization were also presented.
Keywords: Permeability diagnosis, ADME, oral absorption, gastrointestinal permeability, transporter, Caco-2 and PAMPA.
Call for Papers in Thematic Issues
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...read more
Related Journals
Anti-Cancer Agents in Medicinal Chemistry
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry
Current Bioactive Compounds
Current Cancer Drug Targets
Combinatorial Chemistry & High Throughput Screening
Current Cancer Therapy Reviews
Current Diabetes Reviews
Current Drug Safety
Current Drug Targets
Current Drug Therapy
Related Books
Drug Addiction Mechanisms in the Brain
The NLRP3 Inflammasome: An Attentive Arbiter of Inflammatory Response
Botanicals and Natural Bioactives: Prevention and Treatment of Diseases
Software and Programming Tools in Pharmaceutical Research
Objective Pharmaceutics: A Comprehensive Compilation of Questions and Answers for Pharmaceutics Exam Prep
Medicinal Chemistry of Drugs Affecting Cardiovascular and Endocrine Systems
Frontiers In Medicinal Chemistry
Advanced Pharmacy
Plant-derived Hepatoprotective Drugs
Frontiers in Natural Product Chemistry
90
