Article
Endocrinology & Metabolism
Yazeid Alhaidan, Henrik Thybo Christesen, Elena Lundberg, Mohammed A. Al Balwi, Klaus Brusgaard
Summary: This study identified a novel candidate gene, ADCY7, to cause CHI via activation of the GSIS pathway.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Article
Chemistry, Medicinal
Esteban G. Vega Hissi, Antonella B. De Costa Guardamagna, Adriana D. Garro, Cristian R. Falcon, Marko Anderluh, Tihomir Tomasic, Danijel Kikelj, Agustin Yaneff, Carlos A. Davio, Ricardo D. Enriz, Adolfo R. Zurita
Summary: This study reported a derivative of N-(piperidin-4-yl)-1H-pyrrole-2-carboxamide as a new inhibitor for the adenylate cyclase of Giardia lamblia, and developed a model for this specific enzyme. The new inhibitor was found to have a competitive mechanism of action against the enzyme, serving as an excellent starting point for the development of new metabolic inhibitors for G. lamblia.
Article
Cell Biology
Vendula Markova, Lucie Hejnova, Ales Benda, Jiri Novotny, Barbora Melkes
Summary: Beta-arrestins play a crucial role in GPCR-mediated transmembrane signaling processes, but the roles of beta-arrestin 1 and beta-arrestin 2 in MOR-regulated signaling differ, with beta-arrestin 1 more effectively modulating AC activity. This study demonstrates the distinct roles of beta-arrestin isoforms in MOR signaling and reveals their potential interactions with AC.
CELLULAR SIGNALLING
(2021)
Article
Chemistry, Medicinal
Makoto Fushimi, Hannes Buck, Melanie Balbach, Anna Gorovyy, Jacob Ferreira, Thomas Rossetti, Navpreet Kaur, Lonny R. Levin, Jochen Buck, Jonathan Quast, Joop van den Heuvel, Clemens Steegborn, Efrat Finkin-Groner, Stacia Kargman, Mayako Michino, Michael A. Foley, Michael Miller, Nigel J. Liverton, David J. Huggins, Peter T. Meinke
Summary: In this study, a successful design of sAC inhibitor TDI-10229 (12) was described, showing nanomolar inhibition of sAC in both biochemical and cellular assays, with mouse pharmacokinetic properties suitable for in vivo use as a tool compound.
ACS MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Chemistry, Medicinal
Michal Cesnek, Michal Safranek, Martin Dracinsky, Eva Tloust'ova, Helena Mertlikova-Kaiserova, Michael P. Hayes, Val J. Watts, Zlatko Janeba
Summary: A series of potent acyclic nucleoside phosphonates (ANPs) were designed as inhibitors of bacterial ACs, showing substantial selectivity and significant inhibitory effects in cell-based and cell-free assays. These compounds represent the most effective ACT/EF inhibitors based on ANPs reported to date.
Article
Chemistry, Medicinal
Meredith S. Eno, Jason D. Brubaker, John E. Campbell, Chris De Savi, Timothy J. Guzi, Brett D. Williams, Douglas Wilson, Kevin Wilson, Natasja Brooijmans, Joseph Kim, Aysegul Ozen, Emanuele Perola, John Hsieh, Victoria Brown, Kristina Fetalvero, Andrew Garner, Zhuo Zhang, Faith Stevison, Rich Woessner, Jatinder Singh, Yoav Timsit, Caitlin Kinkema, Clare Medendorp, Christopher Lee, Faris Albayya, Alena Zalutskaya, Stefanie Schalm, Thomas A. Dineen
Summary: While EGFR tyrosine kinase inhibitors have revolutionized the treatment of NSCLC, the development of resistance mutations remains a challenge. This study introduces a novel reversible inhibitor, BLU-945, that shows promising activity against different resistance mutations. Clinical trials are currently underway to evaluate its efficacy and safety.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Mohamed Hagras, Moshira A. El Deeb, Heba S. A. Elzahabi, Eslam B. Elkaeed, Ahmed B. M. Mehany, Ibrahim H. Eissa
Summary: Newly synthesized quinoline derivatives exhibited superior cytotoxic activities and inhibitory effects against tubulin polymerisation in human cancer cell lines, potentially serving as promising anticancer agents.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Wei Liu, Youyou He, Zhongjie Guo, Miaomiao Wang, Xiaodong Han, Hairui Jia, Jin He, Shanshan Miao, Shengzheng Wang
Summary: The study aimed to design and optimize analogues of 2-aryl-4-amide-quinoline derivatives targeting the colchicine binding site of tubulin. Analogues C1 similar to J2 were obtained with diverse substituents and scaffolds. Among them, G13 analogue with a hydroxymethyl group exhibited good tubulin polymerisation inhibitory activity (IC50 = 13.5 μM) and potent antiproliferative activity (IC50 values: 0.65 μM to 0.90 μM). G13 effectively inhibited migration, invasion, and angiogenesis of MDA-MB-231 cells, and induced intracellular ROS increase, MMP decrease, and microtubule network fragmentation and disassembly. Moreover, G13 demonstrated significant in vivo antitumour efficacy in MDA-MB-231 xenograft model (TGI = 38.2%; i.p., 30 mg/kg).
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2023)
Article
Ophthalmology
Shakarr V. V. Wiggins, Ryan Schreiner, Jacob Ferreira, Alan D. D. Marmorstein, Lonny R. R. Levin, Jochen Buck
Summary: This study investigated whether a clinically used carbonic anhydrase inhibitor (CAIs) can modulate intraocular pressure (IOP) through soluble adenylyl cyclase (sAC) signaling. IOP was measured 1 h after topical treatment with brinzolamide, a topically applied and clinically used CAIs, using direct cannulation of the anterior chamber in sAC knockout (KO) mice or C57BL/6J mice in the presence or absence of the sAC inhibitor (TDI-10229). The results showed that mice treated with the sAC inhibitor TDI-10229 had elevated IOP. On the other hand, CAIs treatment significantly decreased increased IOP in wild-type, sAC KO mice, as well as TDI-10229-treated mice. These findings suggest that inhibiting carbonic anhydrase reduces IOP independently from sAC in mice, and brinzolamide regulates IOP through a signaling cascade that does not involve sAC.
JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS
(2023)
Article
Multidisciplinary Sciences
Rumiana Simeonova, Vessela Vitcheva, Ivanka Kostadinova, Iva Valkova, Irena Philipova, Georgi Stavrakov, Nikolai Danchev, Irini Doytchinova
Summary: This study evaluated in vivo activities of novel AChE inhibitors with dual-site binding, revealing that one exhibited toxicity while the other only slightly improved memory functions, indicating that the bulkiness of inhibitors may influence brain bioavailability and should be considered in the design of multi-target ligands for Alzheimer's disease treatment.
COMPTES RENDUS DE L ACADEMIE BULGARE DES SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Grace Victoria Govada, Sabbasani Rajasekhara Reddy
Summary: An efficient metal-free approach for site selective C-N coupling reaction of benzo[d]isoxazole and 2H-chromene derivatives has been designed and developed against AchE. The synthesized BC derivatives displayed potent activity and high selectivity against AChE inhibition, with compound 4l showing the lowest binding energy of -11.2260 kcal/mol. These BC analogs hold potential for promoting suitable studies in medicinal chemistry research.
CHEMISTRY & BIODIVERSITY
(2023)
Article
Biochemistry & Molecular Biology
Mesfer Al Shahrani, Mohammad Abohassan, Mohammad Y. Alshahrani, Abdulrahim R. Hakami, Prasanna Rajagopalan
Summary: CB-1, a novel and potent dual B-Raf/c-Raf inhibitor, was effective against colon cancer cells expressing wild-type and mutant variants of B-Raf. Experimental results showed that CB-1 can inhibit cell proliferation by reducing B-Raf expression and inducing apoptosis, making it a potential therapeutic drug for colon cancer.
JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN
(2021)
Article
Chemistry, Medicinal
Satyanarayana Pochampally, Kelli L. Hartman, Rui Wang, Jiaxing Wang, Mi-Kyung Yun, Keyur Parmar, Hyunseo Park, Bernd Meibohm, Stephen W. White, Wei Li, Duane D. Miller
Summary: By modifying the pyrimidine dihydroquinoxalinone scaffold, we discovered a new tubulin-polymerization inhibitor, compound 12k, that exhibited potent anticancer activity and significant tumor growth inhibition in vivo.
ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE
(2023)
Article
Chemistry, Medicinal
Satyanarayana Pochampally, Kelli L. Hartman, Rui Wang, Jiaxing Wang, Mi-Kyung Yun, Keyur Parmar, Hyunseo Park, Bernd Meibohm, Stephen W. White, Wei Li, Duane D. Miller
Summary: A new compound that inhibits cancer cell proliferation has been discovered and shows high anticancer activity and a long half-life. It exhibits significant potency against a wide range of cancer cell lines and has the potential for further preclinical evaluation as a candidate for development.
ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE
(2023)
Article
Neurosciences
Yunjin Lee, Hannah Kim, Ji-Eun Kim, Jin-Young Park, Juli Choi, Jung-Eun Lee, Eun-Hwa Lee, Pyung-Lim Han
MOLECULAR NEUROBIOLOGY
(2018)
Article
Clinical Neurology
Young-Kyoung Ryu, Hye-Yeon Park, Jun Go, Yong-Hoon Kim, Jung Hwan Hwang, Dong-Hee Choi, Jung-Ran Noh, Myungchull Rhee, Pyung-Lim Han, Chul-Ho Lee, Kyoung-Shim Kim
JOURNAL OF NEURAL TRANSMISSION
(2018)
Article
Urology & Nephrology
Qian Wang, Patricia Cobo-Stark, Vishal Patel, Stefan Somlo, Pyung-Lim Han, Peter Igarashi
KIDNEY INTERNATIONAL
(2018)
Article
Cell Biology
Juli Choi, Hye-Jin Kwon, Jung-Eun Lee, Yunjin Lee, Ju-Young Seoh, Pyung-Lim Han
Review
Behavioral Sciences
Eun-Hwa Lee, Pyung-Lim Han
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
(2019)
Article
Neurosciences
Jung-Eun Lee, Hye-Jin Kwon, Juli Choi, Pyung-Lim Han
MOLECULAR NEUROBIOLOGY
(2019)
Editorial Material
Medicine, Research & Experimental
Young Jun Oh, Pyung-Lim Han, C. Justin Lee
EXPERIMENTAL NEUROBIOLOGY
(2019)
Article
Neurosciences
Jung-Eun Lee, So-Young Park, Pyung-Lim Han
Summary: Aging leads to alterations in gene expression in the hippocampus, affecting the ability to cope with stress in mice. Downregulation of SUV39H1 and subsequent changes in its signaling pathways may increase susceptibility to stress in aging individuals. Additionally, the phenolic compound rosmarinic acid shows promise in reversing stress-induced changes and producing antidepressant effects via a distinct mechanism from traditional antidepressants.
MOLECULAR NEUROBIOLOGY
(2021)
Article
Neurosciences
Jin-Young Park, Eun-Hwa Lee, Hye-Jin Kwon, In-Sun Baek, Ji-Seon Seo, Kyoung-Shim Kim, Pyung-Lim Han
Summary: Continual engagement with playable objects in mice subjected to chronic stress can alleviate depressive-like behaviors, possibly by modifying the reward system.
BIOLOGICAL PSYCHIATRY
(2022)
Article
Neurosciences
Juli Choi, Hyejin Kwon, Yoon-Keun Kim, Pyung-Lim Han
Summary: Chronic stress leads to changes in gut microbiota composition, which is related to depressive behavior. The study finds that certain probiotics can ameliorate stress-induced depressive-like behavior by restoring the changes in neurotrophic factors in the hippocampus.
MOLECULAR NEUROBIOLOGY
(2022)
Article
Multidisciplinary Sciences
Eun-Hwa Lee, Jin-Young Park, Hye-Jin Kwon, Pyung-Lim Han
Summary: This study demonstrates that repeated exposure to short-term stress can reverse depressive-like behavior induced by chronic stress. The anti-depressive effects of short-term stress can be mimicked by repeated injection of low doses of glucocorticoids. Additionally, both short-term stress exposure and glucocorticoid injection activate neurons in overlapping brain regions and reverse stress-induced gene expression profiles.
NATURE COMMUNICATIONS
(2021)
Article
Medicine, Research & Experimental
Yunjin Lee, Pyung-Lim Han
EXPERIMENTAL NEUROBIOLOGY
(2019)
Article
Medicine, Research & Experimental
Juli Choi, Yoon-Keun Kim, Pyung-Lim Han
EXPERIMENTAL NEUROBIOLOGY
(2019)
Article
Medicine, Research & Experimental
Yunjin Lee, Hannah Kim, Pyung-Lim Han
EXPERIMENTAL NEUROBIOLOGY
(2018)
Article
Medicine, Research & Experimental
Jin-Young Park, So Young Park, Hyejin Kwon, Yumi Song, Boin Yun, Yubin Lee, Yeryung Cho, Ahran Joo, Pyung-Lim Han
EXPERIMENTAL NEUROBIOLOGY
(2018)