Review
Pharmacology & Pharmacy
Yoon-Young Kim, Jin-Soo Kim, Jeong-Hwan Che, Seung-Yup Ku, Byeong-Cheol Kang, Jun-Won Yun
Summary: Immunodeficient animal models serve as valuable tools for stem cell research, with different gene defects resulting in a variety of phenotypes. Selecting the most appropriate immunodeficient strain, target gene, and animal species based on research type, mutant gene effects, and similarity to human immunological features is crucial for guiding researchers in stem cell research.
Article
Biotechnology & Applied Microbiology
Isain Zapata, M. Leanne Lilly, Meghan E. Herron, James A. Serpell, Carlos E. Alvarez
Summary: This study found that multiple genetic markers are associated with canine behavioral traits and diagnoses. Small body size is associated with various problem behaviors, while large body size is associated with increased trainability. Having children in the home is associated with canine anxiety, while illness and other animals in the home are associated with coprophagia. Pit Bull-type dogs are strongly associated with leash pulling behavior.
Review
Toxicology
Paul Baldrick
Summary: Drug development of imaging agents, contrast agents, and radiopharmaceuticals focuses on diagnostics and disease monitoring, requiring different nonclinical safety testing approaches. Regulatory guidelines aim to streamline testing processes, but interaction with regulatory agencies remains crucial to avoid development surprises and delays.
JOURNAL OF APPLIED TOXICOLOGY
(2021)
Article
Chemistry, Medicinal
Payal Rana, Sanaa Khan, Seda Arat, David Potter, Nasir Khan
Summary: This study evaluated liver toxicity signals for 249 approved drugs and identified predictive factors for human liver injury. The findings suggest that liver safety signals observed in animal toxicity studies can be used to predict the risk of DILI in humans.
CHEMICAL RESEARCH IN TOXICOLOGY
(2022)
Article
Agriculture, Dairy & Animal Science
Clodagh M. Kearney, Nicoline M. Korthagen, Saskia G. M. Plomp, Margot C. Labberte, Janny C. de Grauw, P. Rene van Weeren, Pieter A. J. Brama
Summary: This study investigates the use of repeated low-dose lipopolysaccharide (LPS) injections in equine joints as a model for recurrent joint inflammation. The results suggest that this model can produce consistent inflammatory responses with minimal impact on animal welfare, making it a potential refined translational model for studying recurrent joint inflammation.
Article
Medicine, Legal
Paul Baldrick, Andreas Reichl
Summary: The review of 58 non-oncology drug candidates tested in healthy volunteers confirmed the importance of nonclinical pharmacology and toxicology testing in setting clinical starting doses. The starting doses were conservative, with a high margin of safety observed in both small molecules and biopharmaceuticals. The transition from nonclinical testing to Phase I testing was found to be remarkably safe.
REGULATORY TOXICOLOGY AND PHARMACOLOGY
(2021)
Review
Pharmacology & Pharmacy
Michelle Hemkens, Katie Stamp, Lise I. Loberg, Kevin Moreau, Tim Hart
Summary: Targeted protein degraders (TPDs) are a new type of small-molecule drugs that function through the ubiquitin proteasome system (UPS). Since the first clinical trial of ARV-110 in cancer patients in 2019, the field has rapidly grown. However, there are some theoretical concerns regarding the absorption, distribution, metabolism, and excretion (ADME) as well as safety of TPDs. The International Consortium for Innovation and Quality in Pharmaceutical Development (IQ Consortium) Protein Degrader Working Group (WG) conducted surveys to benchmark preclinical practices for TPDs and address these concerns.
DRUG DISCOVERY TODAY
(2023)
Editorial Material
Biotechnology & Applied Microbiology
Francesco Marchetti, Renato Cardoso, Connie L. L. Chen, George R. Douglas, Joanne Elloway, Patricia A. Escobar, Tod Harper Jr, Robert H. Heflich, Darren Kidd, Anthony M. Lynch, Meagan B. Myers, Barbara L. Parsons, Jesse J. Salk, Raja S. Settivari, Stephanie L. Smith-Roe, Kristine L. Witt, Carole Yauk, Robert R. Young, Shaofei Zhang, Sheroy Minocherhomji
Summary: Error-corrected next-generation sequencing (ecNGS) is a promising technology that can significantly impact the field of genetic toxicology. An expert working group convened to discuss the potential applications, advantages, and challenges of implementing ecNGS in nonclinical safety studies.
NATURE REVIEWS DRUG DISCOVERY
(2023)
Review
Biochemistry & Molecular Biology
Tiphaine Raia-Barjat, Margaux Digonnet, Antoine Giraud, Taghreed Ayash, Seline Vancolen, Mohamed Benharouga, Celine Chauleur, Nadia Alfaidy, Guillaume Sebire
Summary: Preterm birth and chorioamnionitis have significant impacts on both infant and maternal health. Effective treatments and diagnostic methods are still lacking. Animal models can provide insights into the underlying mechanisms and aid in the development of novel therapies.
Article
Chemistry, Medicinal
Raya Stoyanova, Paul Maximilian Katzberger, Leonid Komissarov, Aous Khadhraoui, Lisa Sach-Peltason, Katrin Groebke Zbinden, Torsten Schindler, Nenad Manevski
Summary: This study used a dataset of mouse and rat PK studies at Roche to predict PK properties, such as plasma clearance (CLp), volume of distribution at steady-state (Vss), and oral bioavailability (F), using chemical structure alone. The results showed that AutoGluon, Gaussian Process Regressor (GP), and ChemProp had the best performance. Various methods, such as prediction variance, molecular clustering, and dimensionality-reduction, provided valuable insights into prediction uncertainty and applicability domains. SHAPley Additive exPlanations (SHAPs) highlighted molecular features contributing to the prediction outcomes of Vss, providing explanations for drug design.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Review
Neurosciences
Garikoitz Azkona, Rosario Sanchez-Pernaute
Summary: Animal models are crucial in neuroscience research, but there are recurring issues in data collection and interpretation, a lack of biomarkers, and an over-reliance on mice, leading to low translation efficiency. Non-human primates, with their higher brain complexity and similarity to humans, can provide more relevant translational information. Therefore, resources for training, education, husbandry, and data sharing should be prioritized to improve translational efficiency.
PROGRESS IN NEUROBIOLOGY
(2022)
Review
Chemistry, Multidisciplinary
Saweta Garg, Ashwin Sachdeva, Marloes Peeters, Jake McClements
Summary: Prostate cancer is the second most common male cancer, causing over 375,000 deaths annually. Prostate specific antigen (PSA) is a crucial biomarker for prostate cancer, and measuring PSA levels is important for diagnosis. However, current automated immunoassays require specialized equipment and trained personnel, resulting in high costs and limited accessibility. The development of point-of-care (PoC) PSA tests that offer accurate, low-cost, and rapid results is therefore a priority. This review evaluates the translational advantages and limitations of emerging laboratory-level and commercial PoC tests for PSA determination, and suggests ways to optimize their potential for clinical implementation and global improvement in prostate cancer diagnosis.
Review
Medicine, General & Internal
Vinamr Rastogi, Sanne J. M. Stefens, Judith Houwaart, Hence J. M. Verhagen, Jorg L. de Bruin, Ingrid van der Pluijm, Jeroen Essers
Summary: Aortic aneurysms are dilations of the aorta that can be fatal upon rupture. Diagnostic radiological techniques such as ultrasound, MRI, and CT are used for early diagnosis and follow-up, but have limitations in predicting aneurysm enlargement or rupture risk. Molecular imaging techniques show potential for understanding aneurysm pathogenesis and facilitating early diagnostic analysis.
FRONTIERS IN MEDICINE
(2022)
Article
Cardiac & Cardiovascular Systems
Yaoshan Dun, Thomas P. Olson, Jeffrey W. Ripley-Gonzalez, Kangling Xie, Wenliang Zhang, Ying Cai, Yuan Liu, Yanan Shen, Nanjiang Zhou, Xun Gong, Suixin Liu
Summary: This 18-year cross-sectional study provides data on the safety of exercise testing in the clinical Chinese population. The low rate of adverse events related to exercise testing might be due to changes in clinical practice over time.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2021)
Article
Medicine, Legal
Paul Baldrick
Summary: In the past few years, therapies have been developed for COVID-19 vaccination and treatment. Nonclinical studies were conducted to obtain authorization, and it was found that the number and types of studies required for regulatory agency authorization have not been reduced.
REGULATORY TOXICOLOGY AND PHARMACOLOGY
(2022)
Editorial Material
Toxicology
Thomas B. Knudsen, Douglas A. Keller, Miriam Sander, Edward W. Carney, Nancy G. Doerrer, David L. Eaton, Suzanne Compton Fitzpatrick, Kenneth L. Hastings, Donna L. Mendrick, Raymond R. Tice, Paul B. Watkins, Maurice Whelan
TOXICOLOGICAL SCIENCES
(2015)
Letter
Reproductive Biology
Paul A. Andrews, Douglas A. Keller
REPRODUCTIVE TOXICOLOGY
(2016)
Article
Toxicology
Daland R. Juberg, Thomas B. Knudsen, Miriam Sander, Nancy B. Beck, Elaine M. Faustman, Donna L. Mendrick, John R. Fowle, Thomas Hartung, Raymond R. Tice, Emmanuel Lemazurier, Richard A. Becker, Suzanne Compton Fitzpatrick, George P. Daston, Alison Harrill, Ronald N. Hines, Douglas A. Keller, John C. Lipscomb, David Watson, Tina Bahadori, Kevin M. Crofton
TOXICOLOGICAL SCIENCES
(2017)
Editorial Material
Medicine, Research & Experimental
Lorna Ewart, Kristin Fabre, Ananthsrinivas Chakilam, Yvonne Dragan, David B. Duignan, Jeetu Eswaraka, Jinping Gan, Peggy Guzzie-Peck, Monicah Otieno, Claire G. Jeong, Douglas A. Keller, Sonia M. de Morais, Jonathan A. Phillips, William Proctor, Radhakrishna Sura, Terry Van Vleet, David Watson, Yvonne Will, Danilo Tagle, Brian Berridge
EXPERIMENTAL BIOLOGY AND MEDICINE
(2017)
Article
Pathology
Sherry J. Morgan, Jessica Couch, Peggy Guzzie-Peck, Douglas A. Keller, Ray Kemper, Monicah A. Otieno, Robert J. Schulingkamp, Thomas W. Jones
TOXICOLOGIC PATHOLOGY
(2017)
Article
Pathology
Frank D. Sistare, Daniel Morton, Carl Alden, Joel Christensen, Douglas Keller, Sandra De Jonghe, Richard D. Storer, M. Vijayaraj Reddy, Andrew Kraynak, Bruce Trela, Jean-Guy Bienvenu, Sivert Bjurstrom, Vanessa Bosmans, David Brewster, Karyn Colman, Mark Dominick, John Evans, James R. Hailey, Lewis Kinter, Matt Liu, Charles Mahrt, Dirk Marien, James Myer, Richard Perry, Daniel Potenta, Arthur Roth, Philip Sherratt, Thomas Singer, Rabih Slim, Keith Soper, Ronny Fransson-Steen, James Stoltz, Oliver Turner, Susan Turnquist, Marjolein van Heerden, Jochen Woicke, Joseph J. DeGeorge
TOXICOLOGIC PATHOLOGY
(2011)
Article
Toxicology
Douglas A. Keller, Daland R. Juberg, Natasha Catlin, William H. Farland, Frederick G. Hess, Douglas C. Wolf, Nancy G. Doerrer
TOXICOLOGICAL SCIENCES
(2012)
Article
Chemistry, Medicinal
Chu-Biao Xue, Lihua Chen, Ganfeng Cao, Ke Zhang, Anlai Wang, David Meloni, Joseph Glenn, Rajan Anand, Michael Xia, Ling Kong, Taisheng Huang, Hao Feng, Changsheng Zheng, Mei Li, Laurine Galya, Jiacheng Zhou, Niu Shin, Fredric Baribaud, Kim Solomon, Peggy Scherle, Bitao Zhao, Sharon Diamond, Tom Emm, Douglas Keller, Nancy Contel, Swamy Yeleswaram, Kris Vaddi, Gregory Hollis, Robert Newton, Steven Friedman, Brian Metcalf
ACS MEDICINAL CHEMISTRY LETTERS
(2010)
Article
Physiology
Bruce A. Corliss, Leon J. Delalio, T. C. Stevenson Keller, Alex S. Keller, Douglas A. Keller, Bruce H. Corliss, Jody M. Beers, Shayn M. Peirce, Brant E. Isakson
FRONTIERS IN PHYSIOLOGY
(2019)
Review
Biochemical Research Methods
Matthew F. Peters, Allison L. Choy, Carmen Pin, Derek J. Leishman, Annie Moisan, Lorna Ewart, Peggy J. Guzzie-Peck, Radhakrishna Sura, Douglas A. Keller, Clay W. Scott, Kyle L. Kolaja
Review
Biochemical Research Methods
Jonathan A. Phillips, Taraka Sai Pavan Grandhi, Myrtle Davis, Jean-Charles Gautier, Niresh Hariparsad, Douglas Keller, Radhakrishna Sura, Terry R. Van Vleet
Review
Biochemical Research Methods
Andreas R. Baudy, Monicah A. Otieno, Philip Hewitt, Jinping Gan, Adrian Roth, Douglas Keller, Radhakrishna Sura, Terry R. Van Vleet, William R. Proctor
Article
Pharmacology & Pharmacy
J. S. Prescott, P. A. Andrews, R. W. Baker, M. S. Bogdanffy, F. O. Fields, D. A. Keller, D. M. Lapadula, N. M. Mahoney, D. E. Paul, S. J. Platz, D. M. Reese, S. A. Stoch, J. J. DeGeorge
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2017)
Article
Toxicology
J MacDonald, JE French, RJ Gerson, J Goodman, T Inoue, A Jacobs, P Kasper, D Keller, A Lavin, G Long, B McCullough, FD Sistare, R Storer, JW van der Laan
TOXICOLOGICAL SCIENCES
(2004)