Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
A series of novel M inhibitors was designed and synthesized to combat the coronavirus, such as HCoV-OC43 and SARS-CoV-2, and several compounds showed comparable antiviral activity to nirmatrelvir. Among them, an octahydroindole-based peptidomimetic covalent inhibitor showed strong inhibitory activity against Ms and exhibited broad-spectrum anticoronavirus activity with EC values ranging from 0.027 to 4.41 μM. Besides, this compound displayed potent antiviral activity against EV71. Compared to , displayed better pharmacokinetic properties, and the value of oral bioavailability in CD-1 mice and Beagle dogs was improved to 10.4 and 10.2%, respectively. In addition, oral treatment with could significantly reduce the viral loads of HCoV-OC43 in mice, and compound could also effectively reduce lung viral loads in a K18-hACE2 transgenic mouse model without ritonavir. Taken together, compound is a promising orally bioavailable broad-spectrum antiviral drug candidate that deserves further research.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1021/acs.jmedchem.4c03024 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
The Discovery of RP-2119: A Potent, Selective, and Orally Bioavailable Polθ ATPase Inhibitor.
J Med Chem
September 2025
Repare Therapeutics, 7171 Frederick-Banting, Building 2, H4S 1Z9 Montréal, Québec, Canada.
DNA polymerase theta (Polθ) plays a critical role in repairing DNA double-strand breaks through microhomology-mediated end joining (MMEJ) and has emerged as a key synthetic lethal drug target in cancers with homologous recombination (HR) deficiencies. Its inhibition has shown a strong potential to synergize with PARP inhibitors, particularly in tumors with deleterious or mutations. Here, we describe the discovery and preclinical development of RP-2119, a selective, potent, and bioavailable Polθ ATPase inhibitor.
View Article and Find Full Text PDFProfile of NT-0527, a brain penetrant NLRP3 Inflammasome inhibitor suitable as an tool compound for neuroinflammatory disorders.
RSC Med Chem
September 2025
NodThera Ltd. Suite 8, The Mansion, Chesterford Research Park, Little Chesterford, Saffron Walden Essex CB10 1XL UK
Inhibition of the NLRP3 inflammasome has emerged as a high potential treatment paradigm for the treatment of neuroinflammation, with demonstrated anti-neuroinflammatory effects in Parkinson's disease patients and a strong rationale in Alzheimer's disease and amyotrophic lateral sclerosis. To facilitate further progress in this field, brain penetrant NLRP3 inflammasome inhibitors as leads and tool compounds are required. We discovered a small molecule NLRP3 inflammasome inhibitor, NT-0527 (11), and extensively profiled this to reveal a highly potent, selective and brain penetrant compound.
View Article and Find Full Text PDFIt's getting hot in here: Heating up the tumor microenvironment with an oral HO-1 inhibitor.
Sci Immunol
September 2025
Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
A new orally bioavailable HO-1 inhibitor enhances tumor clearance after chemotherapy in mice by enhancing the recruitment of CD8 T cells.
View Article and Find Full Text PDFDiscovery of novel 3-Benzyloxyaminopyridines as orally available and intracranially active selective ROS1 inhibitors for combating the resistant ROS1 mutation.
Eur J Med Chem
August 2025
NMPA Key Laboratory for Research and Evaluation of Drug Metabolism & Guangdong Provincial Key Laboratory of New Drug Screening & Guangdong-Hongkong-Macao Joint Laboratory for New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China. Electronic addr
The selectivity, central nervous system progression and drug-resistant mutations have raised significant concerns regarding the effectiveness of ROS1 inhibitors. Novel entities have been designed through precise molecular simulation. Introducing larger biphenyl groups in the hydrophobic region enhances ROS1 selectivity and improves lipid solubility for better blood-brain barrier penetration.
View Article and Find Full Text PDFImportance: Effective and well-tolerated pharmacotherapies for generalized anxiety disorder (GAD), which is one of the most common psychiatric disorders, are needed.
Objective: To determine the dose-response relationship of MM120 (lysergide D-tartrate) in adults with moderate to severe GAD.
Design, Settings, And Participants: This phase 2b, multicenter, randomized, double-blind, placebo-controlled study enrolled 198 adults aged 18 to 74 years with a primary GAD diagnosis who presented with moderate to severe symptoms (defined by a Hamilton Anxiety Rating Scale [HAM-A] score ≥20) and was conducted at 22 outpatient psychiatric research sites in the US from August 2022 to August 2023.