Article
Endocrinology & Metabolism
Kazunori Kageyama, Rie Hagiwara, Kanako Niioka, Shinobu Takayasu, Makoto Daimon
Summary: Cushing's disease is primarily caused by autonomous production of ACTH from pituitary corticotroph adenomas. SOM230 has potent effects in decreasing ACTH levels in patients with Cushing's disease. Treatment with SOM230 increased β-arrestin1 mRNA levels, while dexamethasone treatment decreased β-arrestin2 mRNA levels.
Article
Biochemistry & Molecular Biology
Iva Zonjic, Lidija-Marija Tumir, Ivo Crnolatac, Filip Supljika, Livio Racane, Sanja Tomic, Marijana Radic Stojkovic
Summary: Interactions between a series of benzothiazole ligands and nucleic acid structures were screened using competition dialysis. Two compounds demonstrated high affinities against 13 nucleic acid structures, while another compound showed high selectivity among the studied compounds. Additionally, some compounds exhibited specific effects on certain nucleic acid structures.
Article
Biochemistry & Molecular Biology
Jens D. Mikkelsen, Sanjay S. Aripaka, Sif Kaad, Burcu A. Pazarlar, Lars Pinborg, Bente Finsen, Andrea Varrone, Benny Bang-Andersen, Jesper F. Bastlund
Summary: A newly developed radioligand [JNJ-64413739] that selectively binds to the purinergic receptor P2X7R has been found to detect neuroinflammation in the brain. The binding properties of JNJ-64413739 in human brain tissue were investigated, and it was found to have different binding abilities in gray and white matter. These findings demonstrate that JNJ-64413739 is suitable for evaluating the distribution and expression of P2X7R in the human brain.
ACS CHEMICAL NEUROSCIENCE
(2023)
Article
Multidisciplinary Sciences
Xiaohua Xue, Aimee De Leon-Tabaldo, Rosa Luna-Roman, Glenda Castro, Michael Albers, Freddy Schoetens, Samuel DePrimo, Damayanthi Devineni, Thomas Wilde, Steve Goldberg, Thomas Hoffmann, Anne M. Fourie, Robin L. Thurmond
Summary: JNJ-61803534 is a potent and selective ROR gamma t inhibitor that effectively inhibits Th17 differentiation and inflammation, demonstrating therapeutic potential in animal models and in vitro experiments.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Kazunori Kageyama, Yasumasa Iwasaki, Yutaka Watanuki, Shingo Murasawa, Kanako Niioka, Mizuki Tasso, Ai Kosugi, Makoto Daimon
Summary: This study investigated the regulatory effects of dexamethasone on Gdf15 expression in murine corticotroph cells and found that GDF15 modulates ACTH synthesis by suppressing Pomc expression, contributing to pituitary stress response and homeostasis.
Article
Oncology
Andrew Chow, Sara Schad, Michael D. Green, Matthew D. Hellmann, Viola Allaj, Nicholas Ceglia, Giulia Zago, Nisargbhai S. Shah, Sai Kiran Sharma, Marissa Mattar, Joseph Chan, Hira Rizvi, Hong Zhong, Cailian Liu, Yonina Bykov, Dmitriy Zamarin, Hongyu Shi, Sadna Budhu, Corrin Wohlhieter, Fathema Uddin, Aditi Gupta, Inna Khodos, Jessica J. Waninger, Angel Qin, Geoffrey J. Markowitz, Vivek Mittal, Vinod Balachandran, Jennifer N. Durham, Dung T. Le, Weiping Zou, Sohrab P. Shah, Andrew McPherson, Katherine Panageas, Jason S. Lewis, Justin S. A. Perry, Elisa de Stanchina, Triparna Sen, John T. Poirier, Jedd D. Wolchok, Charles M. Rudin, Taha Merghoub
Summary: The study revealed that metastatic cancer in the pleural and peritoneal cavities leads to poor clinical outcomes after immune checkpoint blockade therapy, mainly due to the high expression of Tim-4 by cavity-resident macrophages, which suppresses tumor-reactive CD8(+) T cells. Blocking Tim-4 can enhance the efficacy of immunotherapy in these microenvironments.
Article
Biochemistry & Molecular Biology
Joost Neijssen, Rosa M. F. Cardoso, Kristen M. Chevalier, Luus Wiegman, Thomas Valerius, G. Mark Anderson, Sheri L. Moores, Janine Schuurman, Paul W. H. Parren, William R. Strohl, Mark L. Chiu
Summary: This study focused on developing a bispecific antibody targeting EGFR and MET pathways to overcome resistance to targeted therapies in nonsmall cell lung cancer patients. By sequentially screening a panel of BsAbs and selecting the optimal bispecific molecule, amivantamab was generated and demonstrated superior antitumor activity in preclinical models. The unique mode of action of amivantamab may provide benefits to patients with malignancies associated with aberrant EGFR and MET signaling.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Nathalie Mertens, Mark E. Schmidt, Anja Hijzen, Donatienne Van Weehaeghe, Paulien Ravenstijn, Marleen Depre, Jan de Hoon, Koen Van Laere, Michel Koole
Summary: The study evaluated a minimally invasive approach for accurate PET quantification of [F-18]JNJ-64413739 by using postdose MR angiography guided image derived input function (IDIF) along with baseline blood and metabolite data, showing limited bias compared to an invasive arterial input function approach. The results confirmed high correlation and reliability of the new IDIF method, indicating its potential use in repeated PET studies for P2X7R receptor occupancy evaluation.
SCIENTIFIC REPORTS
(2021)
Article
Chemistry, Medicinal
Jun-Wei Xu, Yang-Li Qi, Jian-Wei Wu, Rui-Xiang Yuan, Xiao-Wen Chen, Jian-Qi Li
Summary: A series of potential antipsychotics were synthesized and evaluated, with compound 12a showing nanomolar affinity for specific receptors and demonstrating antipsychotic efficacy in an animal model. These compounds have potential as new antipsychotic drugs with good drug target selectivity.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Immunology
Jusi Wang, Tingyu Chen, Weifeng Tang, Mingqiang Kang, Shuchen Chen
Summary: The study found that the rs2227282 (C > G) and rs2243283 (C > G) loci in the IL4 gene play protective roles in the development of ESCC, reducing the risk for the disease.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Huilin Yang, Umut Y. Ulge, Alfredo Quijano-Rubio, Zachary J. Bernstein, David R. Maestas, Jung-Ho Chun, Wentao Wang, Jian-Xin Lin, Kevin M. Jude, Srujan Singh, Brian T. Orcutt-Jahns, Peng Li, Jody Mou, Liam Chung, Yun-Huai Kuo, Yasmin H. Ali, Aaron S. Meyer, Warren L. Grayson, Nicola M. Heller, K. Christopher Garcia, Warren J. Leonard, Daniel-Adriano Silva, Jennifer H. Elisseeff, David Baker, Jamie B. Spangler
Summary: In this study, IL-4 cytokine mimetics called Neo-4 were designed based on a de novo engineered IL-2 mimetic scaffold. These cytokines can mimic the physiological functions of IL-4 and offer insights into differential IL-4 signaling through type I versus type II receptors. The design workflow of this study can inform the development of targeted cytokine therapeutics.
NATURE CHEMICAL BIOLOGY
(2023)
Article
Chemistry, Medicinal
Anil Karbhari Shinde, Rajesh Kumar Badange, Veena Reballi, Pramod Kumar Achanta, Kumar Bojja, Sravanthi Manchineella, Nageswara Rao Muddana, Ramkumar Subramanian, Raghava Choudary Palacharla, Vijay Benade, Pradeep Jayarajan, Jagadeesh Babu Thentu, Bujji Babu Lingavarapu, Sivasekhar Yarra, Narendra Kagita, Mallikarjuna Rao Doguparthi, Abdul Rasheed Mohammed, Ramakrishna Nirogi
Summary: Compound 45 e, developed through a series of chemical optimizations, has been identified as a potent and selective H3R inverse agonist, with robust efficacy in fighting against dipsogenia induced by histamine. It has shown good oral exposure and half-life, along with significant effects in object recognition task and acetylcholine levels, suggesting potential for further treatment of cognitive disorders associated with Alzheimer's disease.
Article
Pharmacology & Pharmacy
Min Su Kang, Adjia Hamadjida, Dominique Bedard, Stephen G. Nuara, Jim C. Gourdon, Stephen Frey, Arturo Aliaga, Karen Ross, Robert Hopewell, Hussein Bdair, Axel Mathieu, Christine Lucas Tardif, Jean-Paul Soucy, Gassan Massarweh, Pedro Rosa-Neto, Philippe Huot
Summary: In this study, [C-11]-JNJ-42491293 was used as a PET ligand and showed high selectivity for mGlu(2) receptors in vitro. However, PET experiments in rats, macaques, and humans suggested that [C-11]-JNJ-42491293 could interact with a non-mGlu(2) receptor binding site. PET scans in common marmosets revealed that [C-11]-JNJ-42491293 mainly distributed in the midbrain, cerebellum, and thalamus, with the lowest distribution in the pons. Co-administration of the mGlu(2) PAM AZD8529 did not affect the distribution of [C-11]-JNJ-42491293, suggesting no competition between the two ligands.
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
(2023)
Article
Neurosciences
Molly Hodul, Bethany J. Rennich, Eric S. Luth, Caroline L. Dahlberg, Peter Juo
Summary: This study identifies an activity-dependent mechanism that regulates WDR-20 expression and shows that WDR-20 works together with USP-46 and WDR-48 to promote surface levels of the C. elegans AMPAR GLR-1.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Health Care Sciences & Services
Hitoshi Hirakawa, Taro Ikegami, Norimoto Kise, Hidetoshi Kinjyo, Shunsuke Kondo, Shinya Agena, Narumi Hasegawa, Junko Kawakami, Hiroyuki Maeda, Mikio Suzuki
Summary: This study investigated the roles of HPV infection and EGFR exon 20 mutations in sinonasal inverted papilloma (IP) and sinonasal squamous cell carcinoma (SNSCC). HPV DNA was found in a significant percentage of IP, IP-SCC, and SNSCC cases, along with p16 overexpression. EGFR exon 20 mutations were observed in IP and IP-SCC cases but not in SNSCC. The phosphorylation pattern of EGFR with exon 20 mutations resembled that of HPV-related SNSCC and oropharyngeal cancer. Further research is needed to understand the etiology of IP-SCC.
JOURNAL OF PERSONALIZED MEDICINE
(2023)