4.7 Review

Trends in small molecule drug properties: A developability molecule assessment perspective

Related references

Note: Only part of the references are listed.
Article Medicine, Research & Experimental

The Influence of the Strength of Drug-Polymer Interactions on the Dissolution of Amorphous Solid Dispersions

Kweku K. Amponsah-Efah et al.

Summary: The interaction between ketoconazole (KTZ) and poly(acrylic acid) (PAA) helps maintain supersaturation in solution and enhances the ability to resist drug crystallization.

MOLECULAR PHARMACEUTICS (2021)

Article Chemistry, Applied

Implementing Continuous Manufacturing for the Final Methylation Step in the AMG 397 Process to Deliver Key Quality Attributes

Janine K. Tom et al.

Summary: This article discusses process development efforts to improve the final methylation step in the AMG 397 drug substance process, culminating in the execution of a Good Manufacturing Practice (GMP) continuous manufacturing process. Through batch kinetic studies and detailed NMR analysis, the critical factors for consistent reaction conversion and obtaining high purity API were identified. Lessons learned from the manufacturing campaign resulted in the development of a second-generation continuous process, which successfully demonstrated improved reaction processing on a 100 g scale.

ORGANIC PROCESS RESEARCH & DEVELOPMENT (2021)

Article Pharmacology & Pharmacy

Structural characterization and developability assessment of sustained release hydrogels for rapid implementation during preclinical studies

Prashant Agarwal et al.

Summary: Sustained-release formulations are important for converting efficacious molecules into therapeutic products. Research on hydrogel-based drug delivery has focused on synthesizing new materials, but there is limited attention to factors like structural characterization and technology development. Commercially available thermosensitive hydrogel systems have shown potential for delaying drug release, with one system demonstrating higher complex viscosity and slower diffusivity compared to another.

EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES (2021)

Article Chemistry, Medicinal

A Decade of FDA-Approved Drugs (2010-2019): Trends and Future Directions

Dean G. Brown et al.

Summary: Evaluation of 378 novel drugs and 27 biosimilars approved by the U.S. FDA between 2010 and 2019 revealed oncology as the top therapy area, potential increase in clinical development times, and rapid progress in innovation in new modalities.

JOURNAL OF MEDICINAL CHEMISTRY (2021)

Article Pharmacology & Pharmacy

Clinical Pharmacokinetics of Oral Semaglutide: Analyses of Data from Clinical Pharmacology Trials

Rune V. Overgaard et al.

Summary: A population pharmacokinetic model was used to investigate the absorption, distribution, and elimination of oral semaglutide for treating type 2 diabetes. The model accurately described concentration profiles across trials, with factors such as post-dose fasting time and body weight affecting semaglutide exposure. Despite relatively high within-subject variability in oral bioavailability, it was reduced considerably at steady state.

CLINICAL PHARMACOKINETICS (2021)

Article Chemistry, Medicinal

Target-Based Evaluation of Drug-Like Properties and Ligand Efficiencies

Paul D. Leeson et al.

Summary: The study compares the physicochemical properties of drugs approved between 2010-2020 with compounds reported to bind to their efficacious target. It finds that drugs differ from their target comparators in terms of potency, ligand efficiency, and other descriptors. Furthermore, 96% of drugs have values of LE or LLE greater than the median values of their target comparator compounds.

JOURNAL OF MEDICINAL CHEMISTRY (2021)

Article Biochemistry & Molecular Biology

Assessing the Cell Permeability of Bivalent Chemical Degraders Using the Chloroalkane Penetration Assay

Caroline A. Foley et al.

ACS CHEMICAL BIOLOGY (2020)

Article Chemistry, Medicinal

Utility of Physicochemical Properties for the Prediction of Toxicological Outcomes: Takeda Perspective

Tomoya Yukawa et al.

ACS MEDICINAL CHEMISTRY LETTERS (2020)

Review Pharmacology & Pharmacy

Systemic delivery of peptides by the oral route: Formulation and medicinal chemistry approaches

D. J. Brayden et al.

ADVANCED DRUG DELIVERY REVIEWS (2020)

Article Chemistry, Medicinal

Facts, Patterns, and Principles in Drug Discovery: Appraising the Rule of 5 with Measured Physicochemical Data

Christopher P. Tinworth et al.

JOURNAL OF MEDICINAL CHEMISTRY (2020)

Review Multidisciplinary Sciences

Multispecific drugs herald a new era of biopharmaceutical innovation

Raymond J. Deshaies

NATURE (2020)

Article Biochemistry & Molecular Biology

Improving Membrane Permeation in the Beyond Rule-of-Five Space by Using Prodrugs to Mask Hydrogen Bond Donors

Nicholas Barlow et al.

ACS CHEMICAL BIOLOGY (2020)

Review Pharmacology & Pharmacy

Fsp(3): A new parameter for drug-likeness

Wenxiu Wei et al.

DRUG DISCOVERY TODAY (2020)

Article Chemistry, Medicinal

The Most Common Functional Groups in Bioactive Molecules and How Their Popularity Has Evolved over Time

Peter Ertl et al.

JOURNAL OF MEDICINAL CHEMISTRY (2020)

Article Chemistry, Medicinal

Two Decades under the Influence of the Rule of Five and the Changing Properties of Approved Oral Drugs

Michael D. Shultz

JOURNAL OF MEDICINAL CHEMISTRY (2019)

Article Chemistry, Organic

Molecular Complexity as a Driver for Chemical Process Innovation in the Pharmaceutical Industry

Seb Caille et al.

JOURNAL OF ORGANIC CHEMISTRY (2019)

Article Multidisciplinary Sciences

Molecular Complexity Calculated by Fractal Dimension

Modest von Korff et al.

SCIENTIFIC REPORTS (2019)

Article Chemistry, Medicinal

Are We Opening the Door to a New Era of Medicinal Chemistry or Being Collapsed to a Chemical Singularity?

Yan A. Ivanenkov et al.

JOURNAL OF MEDICINAL CHEMISTRY (2019)

Article Multidisciplinary Sciences

The clinical KRAS(G12C) inhibitor AMG 510 drives anti-tumour immunity

Jude Canon et al.

NATURE (2019)

Article Chemistry, Medicinal

Aminergic GPCR-Ligand Interactions: A Chemical and Structural Map of Receptor Mutation Data

Marton Vass et al.

JOURNAL OF MEDICINAL CHEMISTRY (2019)

Article Chemistry, Medicinal

The CSD Drug Subset: The Changing Chemistry and Crystallography of Small Molecule Pharmaceuticals

Mathew J. Bryant et al.

JOURNAL OF PHARMACEUTICAL SCIENCES (2019)

Article Chemistry, Medicinal

SCScore: Synthetic Complexity Learned from a Reaction Corpus

Connor W. Coley et al.

JOURNAL OF CHEMICAL INFORMATION AND MODELING (2018)

Article Chemistry, Medicinal

Impact of Dynamically Exposed Polarity on Permeability and Solubility of Chameleonic Drugs Beyond the Rule of 5

Matteo Rossi Sebastiano et al.

JOURNAL OF MEDICINAL CHEMISTRY (2018)

Article Chemistry, Medicinal

Matched Molecular Pair Analysis on Large Melting Point Datasets: A Big Data Perspective

Michael Withnall et al.

CHEMMEDCHEM (2018)

Article Biochemistry & Molecular Biology

Target class drug discovery

Kimberly D. Barnash et al.

NATURE CHEMICAL BIOLOGY (2017)

Letter Biochemistry & Molecular Biology

The Drug Repurposing Hub: a next-generation drug library and information resource

Steven M. Corsello et al.

NATURE MEDICINE (2017)

Review Chemistry, Medicinal

Review and analysis of FDA approved drugs using lipid-based formulations

Ronak Savla et al.

DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY (2017)

Review Pharmacology & Pharmacy

The many roles of molecular complexity in drug discovery

Oscar Mendez-Lucio et al.

DRUG DISCOVERY TODAY (2017)

Review Biochemistry & Molecular Biology

Combinatorial chemistry in drug discovery

Ruiwu Liu et al.

CURRENT OPINION IN CHEMICAL BIOLOGY (2017)

Review Chemistry, Medicinal

Toxicology Strategies for Drug Discovery: Present and Future

Eric A. G. Blomme et al.

CHEMICAL RESEARCH IN TOXICOLOGY (2016)

Article Biochemistry & Molecular Biology

WITHDRAWN-a resource for withdrawn and discontinued drugs

Vishal B. Siramshetty et al.

NUCLEIC ACIDS RESEARCH (2016)

Article Pharmacology & Pharmacy

Lipophilicity in Drug Development: Too Much or Not Enough?

Christel A. S. Bergstrom et al.

AAPS JOURNAL (2016)

Review Pharmacology & Pharmacy

Molecular inflation, attrition and the rule of five

Paul D. Leeson

ADVANCED DRUG DELIVERY REVIEWS (2016)

Review Pharmacology & Pharmacy

Quantifying the chameleonic properties of macrocycles and other high-molecular-weight drugs

Adrian Whitty et al.

DRUG DISCOVERY TODAY (2016)

Review Chemistry, Multidisciplinary

Inherent formulation issues of kinase inhibitors

M. Herbrink et al.

JOURNAL OF CONTROLLED RELEASE (2016)

Review Chemistry, Multidisciplinary

Facts and fictions about polymorphism

Aurora J. Cruz-Cabeza et al.

CHEMICAL SOCIETY REVIEWS (2015)

Article Toxicology

Computational toxicology: Its essential role in reducing drug attrition

R. T. Naven et al.

HUMAN & EXPERIMENTAL TOXICOLOGY (2015)

Article Medicine, Research & Experimental

Drug-Polymer-Water Interaction and Its Implication for the Dissolution Performance of Amorphous Solid Dispersions

Yuejie Chen et al.

MOLECULAR PHARMACEUTICS (2015)

Article Biotechnology & Applied Microbiology

An analysis of the attrition of drug candidates from four major pharmaceutical companies

Michael J. Waring et al.

NATURE REVIEWS DRUG DISCOVERY (2015)

Review Chemistry, Multidisciplinary

Conformational Polymorphism

Aurora J. Cruz-Cabeza et al.

CHEMICAL REVIEWS (2014)

Review Pharmacology & Pharmacy

Novel tactics for designing water-soluble molecules in drug discovery

Michael A. Walker

EXPERT OPINION ON DRUG DISCOVERY (2014)

Article Chemistry, Medicinal

Rings in Drugs

Richard D. Taylor et al.

JOURNAL OF MEDICINAL CHEMISTRY (2014)

Article Chemistry, Medicinal

Acidic and Basic Drugs in Medicinal Chemistry: A Perspective

Paul S. Charifson et al.

JOURNAL OF MEDICINAL CHEMISTRY (2014)

Article Medicine, Research & Experimental

Computational Predictions of Glass-Forming Ability and Crystallization Tendency of Drug Molecules

Amjad Alhalaweh et al.

MOLECULAR PHARMACEUTICS (2014)

Editorial Material Biotechnology & Applied Microbiology

R&D productivity: on the comeback trail

Ulrik Schulze et al.

NATURE REVIEWS DRUG DISCOVERY (2014)

Article Biotechnology & Applied Microbiology

The role of ligand efficiency metrics in drug discovery

Andrew L. Hopkins et al.

NATURE REVIEWS DRUG DISCOVERY (2014)

Article Chemistry, Medicinal

A Chemogenomic Analysis of Ionization Constants-Implications for Drug Discovery

David T. Manallack et al.

CHEMMEDCHEM (2013)

Article Biochemistry & Molecular Biology

Inflation of correlation in the pursuit of drug-likeness

Peter W. Kenny et al.

JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN (2013)

Editorial Material Biotechnology & Applied Microbiology

Does size matter in R&D productivity? If not, what does?

Michael Ringel et al.

NATURE REVIEWS DRUG DISCOVERY (2013)

Review Pharmacology & Pharmacy

Strategies to Address Low Drug Solubility in Discovery and Development

Hywel D. Williams et al.

PHARMACOLOGICAL REVIEWS (2013)

Article Pharmacology & Pharmacy

Mechanically Induced Amorphization of Drugs: A Study of the Thermal Behavior of Cryomilled Compounds

Niraj S. Trasi et al.

AAPS PHARMSCITECH (2012)

Review Chemistry, Medicinal

How hydrogen bonds impact P-glycoprotein transport and permeability

Prashant V. Desai et al.

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS (2012)

Article Chemistry, Medicinal

Use of 3D Properties to Characterize Beyond Rule-of-5 Property Space for Passive Permeation

Cristiano R. W. Guimaraes et al.

JOURNAL OF CHEMICAL INFORMATION AND MODELING (2012)

Article Chemistry, Medicinal

Relating Molecular Properties and in Vitro Assay Results to in Vivo Drug Disposition and Toxicity Outcomes

Jeffrey J. Sutherland et al.

JOURNAL OF MEDICINAL CHEMISTRY (2012)

Article Chemistry, Medicinal

Structural Modifications that Alter the P-Glycoprotein Efflux Properties of Compounds

Stephen A. Hitchcock

JOURNAL OF MEDICINAL CHEMISTRY (2012)

Article Pharmacology & Pharmacy

Physicochemical Property Space of Hepatobiliary Transport and Computational Models for Predicting Rat Biliary Excretion

Manthena V. S. Varma et al.

DRUG METABOLISM AND DISPOSITION (2012)

Article Chemistry, Medicinal

Improved Pharmacokinetics of AMG 517 Through Co-crystallization Part 2: Analysis of 12 Carboxylic Acid Co-crystals

Mary K. Stanton et al.

JOURNAL OF PHARMACEUTICAL SCIENCES (2011)

Article Biotechnology & Applied Microbiology

The influence of the 'organizational factor' on compound quality in drug discovery

Paul D. Leeson et al.

NATURE REVIEWS DRUG DISCOVERY (2011)

Review Biochemistry & Molecular Biology

Impact of ion class and time on oral drug molecular properties

Paul D. Leeson et al.

MEDCHEMCOMM (2011)

Article Biophysics

Exploring the P-Glycoprotein Binding Cavity with Polyoxyethylene Alkyl Ethers

Xiaochun Li Blatter et al.

BIOPHYSICAL JOURNAL (2010)

Review Pharmacology & Pharmacy

Lipophilicity in drug discovery

Michael J. Waring

EXPERT OPINION ON DRUG DISCOVERY (2010)

Article Chemistry, Medicinal

A Classification System to Assess the Crystallization Tendency of Organic Molecules from Undercooled Melts

Jared A. Baird et al.

JOURNAL OF PHARMACEUTICAL SCIENCES (2010)

Article Multidisciplinary Sciences

Structure of the Human Dopamine D3 Receptor in Complex with a D2/D3 Selective Antagonist

Ellen Y. T. Chien et al.

SCIENCE (2010)

Review Biochemical Research Methods

Formulation and manufacturability of biologics

Steven J. Shire

CURRENT OPINION IN BIOTECHNOLOGY (2009)

Article Chemistry, Medicinal

Escape from Flatland: Increasing Saturation as an Approach to Improving Clinical Success

Frank Lovering et al.

JOURNAL OF MEDICINAL CHEMISTRY (2009)

Article Chemistry, Medicinal

Developability Assessment in Pharmaceutical Industry: An Integrated Group Approach for Selecting Developable Candidates

Vishal Saxena et al.

JOURNAL OF PHARMACEUTICAL SCIENCES (2009)

Article Chemistry, Medicinal

Physiochemical drug properties associated with in vivo toxicological outcomes

Jason D. Hughes et al.

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS (2008)

Article Chemistry, Medicinal

Straightforward recursive partitioning model for discarding insoluble compounds in the drug discovery process

Claudia Lamanna et al.

JOURNAL OF MEDICINAL CHEMISTRY (2008)

Review Chemistry, Medicinal

Generation of a set of simple, interpretable ADMET rules of thumb

M. Paul Gleeson

JOURNAL OF MEDICINAL CHEMISTRY (2008)

Article Medicine, Research & Experimental

Cocrystal or salt:: Does it really matter?

Christer B. Aakeroy et al.

MOLECULAR PHARMACEUTICS (2007)

Review Biotechnology & Applied Microbiology

Lipids and lipid-based formulations: optimizing the oral delivery of lipophilic drugs

Christopher J. H. Porter et al.

NATURE REVIEWS DRUG DISCOVERY (2007)

Review Chemistry, Medicinal

Structure-brain exposure relationships

Stephen A. Hitchcock et al.

JOURNAL OF MEDICINAL CHEMISTRY (2006)

Article Chemistry, Medicinal

Dependence of molecular properties on proteomic family for marketed oral drugs

Michal Vieth et al.

JOURNAL OF MEDICINAL CHEMISTRY (2006)

Article Chemistry, Medicinal

A bioavailability score

YC Martin

JOURNAL OF MEDICINAL CHEMISTRY (2005)

Article Chemistry, Multidisciplinary

ADME evaluation in drug discovery. 5. Correlation of Caco-2 permeation with simple molecular properties

TJ Hou et al.

JOURNAL OF CHEMICAL INFORMATION AND COMPUTER SCIENCES (2004)

Article Chemistry, Medicinal

Time-related differences in the physical property profiles of oral drugs

PD Leeson et al.

JOURNAL OF MEDICINAL CHEMISTRY (2004)

Article Chemistry, Medicinal

Characteristic physical properties and structural fragments of marketed oral drugs

M Vieth et al.

JOURNAL OF MEDICINAL CHEMISTRY (2004)

Article Biotechnology & Applied Microbiology

Prospects for productivity

B Booth et al.

NATURE REVIEWS DRUG DISCOVERY (2004)

Article Biochemistry & Molecular Biology

Construction of a sequence motif characteristic of aminergic G protein-coupled receptors

ES Huang

PROTEIN SCIENCE (2003)

Article Biochemical Research Methods

Hydrogen bonding descriptors in the prediction of human in vivo intestinal permeability

S Winiwarter et al.

JOURNAL OF MOLECULAR GRAPHICS & MODELLING (2003)

Article Chemistry, Medicinal

Molecular properties that influence the oral bioavailability of drug candidates

DF Veber et al.

JOURNAL OF MEDICINAL CHEMISTRY (2002)

Article Chemistry, Multidisciplinary

Ritonavir: An extraordinary example of conformational polymorphism

J Bauer et al.

PHARMACEUTICAL RESEARCH (2001)

Article Chemistry, Applied

Crystallization and polymorphism of conformationally flexible molecules: Problems, patterns, and strategies

L Yu et al.

ORGANIC PROCESS RESEARCH & DEVELOPMENT (2000)