Article
Chemistry, Analytical
Yinghua Guo, Lei Yin, Xuhong Qian, Youjun Yang, Xiao Luo
Summary: A new principle called PET/d-PET (PdP) pairing is reported for the rational design of two-channel probes. Two fluorophores in a PdP-type probe mutually quench their fluorescence. When an analyte-of-interest is present, the PdP pair converts to a FRET pair for signaling. Rh-TROX, which combines a rhodamine fluorophore with an ROS-sensitive probe (TotalROX), is an embodiment of this principle. The PdP principle offers the possibility to develop probes for a range of substrates.
ANALYTICAL CHEMISTRY
(2023)
Article
Pharmacology & Pharmacy
Ian E. Templeton, Karen Rowland-Yeo, Hannah M. Jones, Christopher J. Endres, Ariel R. Topletz-Erickson, Hao Sun, Anthony J. Lee
Summary: A physiologically-based pharmacokinetic (PBPK) model was developed to simulate plasma concentrations of tucatinib. The model accurately predicted tucatinib concentrations and drug-drug interactions in different scenarios after refinement and validation with clinical data.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Infectious Diseases
Marcus Tindall, Michael J. Chappell, James W. T. Yates
Summary: Mathematical modelling has played a significant role in optimizing the use of antimicrobial treatments. This article discusses the key processes that should be captured by such modelling, with a particular emphasis on quantifying the response of the host immune system and presenting a novel model structure.
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2022)
Review
Chemistry, Multidisciplinary
Andrew R. Willmer, Jiayi Nie, Mery Vet George De la Rosa, Winnie Wen, Steven Dunne
Summary: Clofazimine can be used to construct inert and stimulus responsive drug depots within cells. It self-assembles into stable drug inclusions that accumulate in macrophages and can be activated to combat infections.
JOURNAL OF CONTROLLED RELEASE
(2022)
Article
Pharmacology & Pharmacy
Meng Fu, Lin Luo, Sheng Feng, Hongda Lin, Zekun Lu, Fei Gu, Yang Fan, Bing Wu, Jianying Huang, Kai Shen
Summary: This study evaluated the effects of SHR0302 on the pharmacokinetics of cytochrome P450 (CYP) probe substrates. The results demonstrated that co-administration of SHR0302 did not have a clinically meaningful effect on the exposure of drugs metabolized by CYP3A4, CYP2C8, CYP2C9 and CYP2C19 in healthy subjects.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2023)
Review
Pharmacology & Pharmacy
Mary E. E. Palmer, Lauren J. J. Andrews, Taylor C. C. Abbey, Ashley E. E. Dahlquist, Eric Wenzler
Summary: A deep understanding of pharmacokinetic and pharmacodynamic properties is crucial for optimizing drug use and increasing the chances of successful drug development. Recent advances in pharmacokinetic and pharmacodynamic studies have renewed confidence in their value and made them a fundamental component of drug development programs.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Chung-Ping Yu, Pei-Ling Tsai, Pei-Ying Li, Pei-Wen Hsu, Shiuan-Pey Lin, Pei-Dawn Lee Chao, Yu-Chi Hou
Summary: The ingestion of cranberry juice affected the activities and protein levels of P-gp, BCRP, CYP3A4 and CYP2D6.
Review
Chemistry, Multidisciplinary
Yang Ding, Zheng Li, Chenchen Xu, Wenjing Qin, Qiong Wu, Xuchun Wang, Xiamin Cheng, Lin Li, Wei Huang
Summary: Beta-lactam antibiotics are important inventions in treating infections, but the emergence of beta-lactamase in bacteria leads to drug resistance. Various detection methods and inhibitors are available, and designing improved probes may help overcome bacterial resistance.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Biochemistry & Molecular Biology
Giuseppe Zagotto, Marco Bortoli
Summary: Medicinal chemistry is advancing rapidly with the use of new tools and methods, such as considering folding intermediates or the catalytic process of proteins as targets for discovering new hits, as well as machine learning. These advancements are leading to important progress in drug discovery and patient care.
Article
Chemistry, Multidisciplinary
Lara Garcia-Varela, Pascalle Mossel, Pablo Aguiar, Daniel A. Vazquez-Matias, Aren van Waarde, Antoon T. M. Willemsen, Anna L. Bartels, Nicola A. Colabufo, Rudi A. J. O. Dierckx, Philip H. Elsinga, Gert Luurtsema
Summary: This study found that small changes in P-gp function caused by low doses of tariquidar could be detected by [F-18]MC225-K-1 values, confirming the high sensitivity of the radiotracer.
JOURNAL OF CONTROLLED RELEASE
(2022)
Article
Pharmacology & Pharmacy
Louise Breuil, Nora Ziani, Sarah Leterrier, Gaelle Hugon, Fabien Caille, Viviane Bouilleret, Charles Truillet, Maud Goislard, Myriam El Biali, Martin Bauer, Oliver Langer, Sebastien Goutal, Nicolas Tournier
Summary: This study investigated the impact of CYP inducers and inhibitors on the brain and plasma kinetics of [C-11]metoclopramide using PET imaging. The results showed that CYP induction or inhibition had negligible effects on the plasma kinetics and metabolism of [C-11]metoclopramide, but ritonavir significantly increased brain penetration.
Article
Engineering, Environmental
Xin-Fang Zhai, Jing-Jing Fan, Yang Yi, Meng Zhang, Xia Yuan, Xue Qiao, Lei Liang, Min Ye
Summary: This research reports the first sensitive and selective fluorescent off-on UGT1A10 probe substrate called UPr6, which can be used to monitor the function of UGT1A10 in biological systems. Through a collaborative modification strategy, the researchers designed UPr6 by introducing a rigid propyl morpholine group and a methoxy group to the amide and 4'-phenoxy positions, respectively. The study also discovered two natural products from licorice as potent UGT1A10 inhibitors, which improved the sensitivity of CPT-11 against a resistant human cancer cell line. This work established a feasible strategy for designing isoform-specific UGT probe substrates.
CHEMICAL ENGINEERING JOURNAL
(2023)
Review
Pharmacology & Pharmacy
Orestis Kontogiannis, Dimitrios Selianitis, Nefeli Lagopati, Natassa Pippa, Stergios Pispas, Maria Gazouli
Summary: The medical application of nanotechnology in drug delivery has made significant progress in treating various human diseases, offering advantages such as targeted drug delivery, low toxicity, and personalized medicine. Innovative drug delivery carriers using polymers, surfactants, and their combinations have been developed and tested pre-clinically, enabling simultaneous delivery of multiple therapeutic entities and combining therapy with diagnosis. This review focuses on the applications of surfactant-based, polymer-based, and mixed surfactant-polymer nanoparticle drug formulations in the medical field, providing detailed information on the materials used, formulation steps, physicochemical characteristics, and pharmacokinetic behavior of these systems.
Article
Endocrinology & Metabolism
Louise Breuil, Solene Marie, Sebastien Goutal, Sylvain Auvity, Charles Truillet, Wadad Saba, Oliver Langer, Fabien Caille, Nicolas Tournier
Summary: This study investigates differences in vulnerability to P-gp inhibition among radiolabeled substrates and emphasizes the importance of considering partial inhibition of transporter function as a primary criterion in evaluating the sensitivity of radiolabeled substrates to detect moderate but physiologically-relevant changes in transporter function in vivo.
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
(2021)
Review
Cell Biology
Munmun Panda, Surya Kant Tripathi, Gokhan Zengin, Bijesh K. Biswal
Summary: Evodiamine, a major alkaloid component found in the fruit of Evodia rutaecarpa, has shown promising anticancer potential by suppressing cell growth, invasion, and metastasis and inducing apoptosis in various cancers. It modulates aberrant signaling pathways and can enhance the efficacy of chemotherapeutic drugs. Although its bioavailability is poor, efforts have been made to improve it and reduce toxicity. This review summarizes the ongoing research on the mechanisms and therapeutic implications of evodiamine in cancer biology.
CELL BIOLOGY AND TOXICOLOGY
(2023)
Article
Chemistry, Medicinal
Filipa Mota, Alvaro A. Ordonez, George Firth, Camilo A. Ruiz-Bedoya, Michelle T. Ma, Sanjay K. Jain
JOURNAL OF MEDICINAL CHEMISTRY
(2020)
Article
Infectious Diseases
Dewi Lokida, Usman Hadi, Chuen-Yen Lau, Herman Kosasih, C. Jason Liang, Musofa Rusli, Pratiwi Sudarmono, Nurhayati Lukman, Kanti Laras, Rizka Humardewayantie Asdie, Dewi Murniati, I. Made Susila Utama, Risna Halim Mubin, Muhammad Karyana, Muhammad Hussein Gasem, Bachti Alisjahbana
BMC INFECTIOUS DISEASES
(2020)
Article
Radiology, Nuclear Medicine & Medical Imaging
Alvaro A. Ordonez, Sudhanshu Abhishek, Alok K. Singh, Mariah H. Klunk, Babak Benham Azad, Eric O. Aboagye, Laurence Carroll, Sanjay K. Jain
MOLECULAR IMAGING AND BIOLOGY
(2020)
Article
Infectious Diseases
Mansyur Arif, Patricia Tauran, Herman Kosasih, Ninny Meutia Pelupessy, Nurhayana Sennang, Risna Halim Mubin, Pratiwi Sudarmono, Emiliana Tjitra, Dewi Murniati, Anggraini Alam, Muhammad Hussein Gasem, Abu Tholib Aman, Dewi Lokida, Usman Hadi, Ketut Tuti Merati Parwati, Chuen-Yen Lau, Aaron Neal, Muhammad Karyana
PLOS NEGLECTED TROPICAL DISEASES
(2020)
Article
Chemistry, Medicinal
Filipa Mota, Ravindra Jadhav, Camilo A. Ruiz-Bedoya, Alvaro A. Ordonez, Mariah H. Klunk, Joel S. Freundlich, Sanjay K. Jain
ACS INFECTIOUS DISEASES
(2020)
Article
Cell Biology
Oren Gordon, Robert J. Miller, John M. Thompson, Alvaro A. Ordonez, Mariah H. Klunk, Dustin A. Dikeman, Daniel P. Joyce, Camilo A. Ruiz-Bedoya, Lloyd S. Miller, Sanjay K. Jain
DISEASE MODELS & MECHANISMS
(2020)
Article
Infectious Diseases
Abu Tholib Aman, Tri Wibawa, Herman Kosasih, Rizka Humardewayanti Asdie, Ida Safitri, Umi Solekhah Intansari, Yuli Mawarti, Pratiwi Sudarmono, Mansyur Arif, Dwiyanti Puspitasari, Bachti Alisjahbana, Ketut Tuti Merati Parwati, Muhammad Hussein Gasem, Dewi Lokida, Nurhayati Lukman, Teguh Sarry Hartono, Yan Mardian, C. Jason Liang, Sophia Siddiqui, Muhammad Karyana, Chuen-Yen Lau
Summary: This study in Indonesian tertiary hospitals identified the burden, clinical characteristics, and etiologies of SARI. Influenza patients were frequently misdiagnosed, highlighting the need for public health strategies including widespread prevention measures and improved diagnostic capacity.
INFLUENZA AND OTHER RESPIRATORY VIRUSES
(2021)
Review
Infectious Diseases
Michael E. Urbanowski, Alvaro A. Ordonez, Camilo A. Ruiz-Bedoya, Sanjay K. Jain, William R. Bishai
LANCET INFECTIOUS DISEASES
(2020)
Article
Medicine, General & Internal
Alberto Signore, Vera Artiko, Martina Conserva, Guillermina Ferro-Flores, Mick M. Welling, Sanjay K. Jain, Soren Hess, Mike Sathekge
JOURNAL OF CLINICAL MEDICINE
(2020)
Article
Cell Biology
Yingda L. Xie, Veronique R. de Jager, Ray Y. Chen, Lori E. Dodd, Praveen Paripati, Laura E. Via, Dean Follmann, Jing Wang, Keith Lumbard, Saher Lahouar, Stephanus T. Malherbe, Jenna Andrews, Xiang Yu, Lisa C. Goldfeder, Ying Cai, Kriti Arora, Andre G. Loxton, Naadira Vanker, Michael Duvenhage, Jill Winter, Taeksun Song, Gerhard Walzl, Andreas H. Diacon, Clifton E. Barry
Summary: Early bactericidal activity studies in individuals with tuberculosis (TB) monitor daily sputum bacterial counts during experimental drug treatment, providing critical information for the development of new TB drugs. Radiological responses to drug treatment using [F-18]FDG-PET/CT imaging can offer comparative measures of single and combination drug activity that correlate closely with clinical outcomes. Rifampicin-containing drug combinations were most effective in reducing lung lesion volume and associated inflammation, while moxifloxacin did not outperform rifampicin in PET/CT imaging, consistent with recent phase 3 clinical trial results. Synergy was observed between isoniazid and pyrazinamide, with pyrazinamide showing activity limited to lung lesions.
SCIENCE TRANSLATIONAL MEDICINE
(2021)
Article
Chemistry, Multidisciplinary
Brett M. Babin, Gabriela Fernandez-Cuervo, Jessica Sheng, Ori Green, Alvaro A. Ordonez, Mitchell L. Turner, Laura J. Keller, Sanjay K. Jain, Doron Shabat, Matthew Bogyo
Summary: FLASH is a fast, luminescent, and affordable sensor developed for detecting and monitoring drug susceptibility of Mycobacterium tuberculosis (Mtb). It is selective for the Mtb protease Hip1 and can detect low amounts of Mtb cells with high sensitivity within minutes. FLASH can distinguish live from dead cells and has the potential to enhance TB diagnostics and drug resistance monitoring in resource-limited settings.
ACS CENTRAL SCIENCE
(2021)
Article
Biochemical Research Methods
Filipa Mota, Patricia De Jesus, Sanjay K. Jain
Summary: Researchers developed a method to synthesize F-18-FDS for positron emission tomography imaging to visualize infections. Clinical study in 26 patients showed that F-18-FDS PET was safe and could differentiate infections caused by Enterobacterales from other pathologies such as sterile inflammation or cancer.
Article
Microbiology
Jianhao Lai, Swati Shah, Rekeya Knight, Neysha Martinez-Orengo, Reema Patel, Amelia Mitchell, Zeping Wang, Falguni Basuli, Alvaro A. Ordonez, Sanjay K. Jain, Dima A. Hammoud
Summary: The diagnosis of fungal infections, especially with Aspergillus fumigatus, is still challenging. The study found low uptake of the newly described Enterobacterales imaging ligand FDS by A. fumigatus, suggesting that FDS is not a suitable imaging agent for Aspergillus.
Article
Microbiology
Stefanie Krug, Pankaj Prasad, Shiqi Xiao, Shichun Lun, Camilo A. A. Ruiz-Bedoya, Mariah Klunk, Alvaro A. A. Ordonez, Sanjay K. K. Jain, Geetha Srikrishna, Igor Kramnik, William R. R. Bishai
Summary: Despite advances in TB drug development, multidrug resistance remains a major challenge for global TB control. Host-directed therapies, such as inhibition of the integrated stress response (ISR), have the potential to improve the efficacy of tuberculosis antibiotics. In this study, we evaluated the impact of ISR inhibition on bacterial clearance, relapse, and lung pathology in a mouse model of TB. Our findings suggest that adjunctive ISR inhibition can accelerate bacterial clearance, reduce relapse rates, and improve lung health.
Letter
Medicine, General & Internal
Jessica H. Rubens, Petros C. Karakousis, Sanjay K. Jain
NEW ENGLAND JOURNAL OF MEDICINE
(2020)