Previously, we reported a series of novel benzimidazole based Itk inhibitors that exhibited excellent enzymatic potency and selectivity but low microsomal stability. Employing a structure based approach a new series of inhibitors with comparable potency and selectivity to the original series and with a potential for improved microsome stability was identified.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.bmcl.2008.09.017 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
D dopamine / mu opioid receptor interactions in operant conditioning assays of pain-depressed responding and drug-induced rate suppression, and a conditioned place preference procedure: assessment of therapeutic index in male Sprague Dawley rats.
Psychopharmacology (Berl)
January 2025
Department of Psychology, University of New England, Biddeford, ME, USA.
Rationale And Objectives: In vivo receptor interactions vary as a function of behavioral endpoint, with key differences between reflexive and non-reflexive measures that assess the motivational aspects of pain and pain relief. There have been no assessments of D dopamine agonist / mu opioid receptor (MOR) agonist interactions in non-reflexive behavioral measures of pain. We examined the hypothesis that D/MOR mixtures show enhanced effectiveness in blocking pain depressed behaviors while showing decreased side effects such as sedation and drug reward.
View Article and Find Full Text PDFGM-CSF and IL-21-armed oncolytic vaccinia virus significantly enhances anti-tumor activity and synergizes with anti-PD1 immunotherapy in pancreatic cancer.
Front Immunol
January 2025
Sino-British Research Centre for Molecular Oncology, National Centre for International Research in Cell and Gene Therapy, State Key Laboratory of Esophageal Cancer Prevention & Treatment, School of Basic Medical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, China.
Pancreatic cancer is one of the most aggressive cancers and poses significant challenges to current therapies because of its complex immunosuppressive tumor microenvironment (TME). Oncolytic viruses armed with immunoregulatory molecules are promising strategies to overcome limited efficacy and target inaccessible and metastatic tumors. In this study, we constructed a tumor-selective vaccinia virus (VV) with deletions of the TK and A49 genes (VVLΔTKΔA49, VVL-DD) using CRISPR-Cas9-based homologous recombination.
View Article and Find Full Text PDFNext-Generation Carbazole-Linked 1,2,4-Triazole-Thione Derivatives: Strategic Design, Synthesis, Molecular Docking, and Evaluation of Antidiabetic Potential.
ACS Omega
January 2025
Department of Pharmacy, Faculty of Medicine and Health Sciences, An-Najah National University, 00433 Nablus, Palestine.
Currently, available therapies for diabetes cannot achieve normal sugar values in a high percentage of treated patients. This work synthesized a series of carbazole-triazole-thione derivatives, and their potential antidiabetic activity was investigated against the key diabetic enzymes α-amylase and glycosidase. Normal human hepatic stellate cells (LX-2) were employed to assess their cytotoxicity and safety, followed by in vivo testing to investigate the hypoglycemic effect of the most promising agent.
View Article and Find Full Text PDFA review of click chemistry in the synthesis of organophosphorus triazoles and their biological activities.
Eur J Med Chem
January 2025
Department of Chemistry and Earth Sciences, College of Arts and Sciences, Qatar University, Doha, 2713, Qatar. Electronic address:
Organophosphorus compounds, characterized by the incorporation of phosphorus into organic molecules, play a critical role in various fields such as medicine, agriculture, and industry. Their unique electronic properties and versatility make them essential in developing therapeutic agents, pesticides, and materials. One prominent class of organophosphorus compounds is organophosphorus heterocycles, which combine the benefits of both phosphorus and cyclic structures.
View Article and Find Full Text PDFSingle-plate kinome screening in live-cells to enable highly cost-efficient kinase inhibitor profiling.
SLAS Discov
January 2025
Institute for Pharmaceutical Chemistry, Johann Wolfgang Goethe-University, Frankfurt am Main, Germany; Structural Genomics Consortium (SGC), Buchmann Institute for Life Sciences, Frankfurt am Main, Germany; German Cancer Consortium (DKTK)/German Cancer Research Center (DKFZ), DTKT Site Frankfurt-Mainz, Heidelberg, Germany.
Cancer research, cancer treatment, and the field of chemical biology are examples which heavily rely on the discovery of selective kinase inhibitors. While determining on-target potency is often feasible for most laboratories, the equally critical but frequently neglected selectivity screening remains less accessible to the broader scientific community. This limitation can stem from various factors, such as the unavailability of a large number of purified kinases or the costs associated with commercial screening systems.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!