A high throughput screen showed the ability of a 1-amino-2,4-dicyanopyrido[1,2-a]benzimidazole analogue to directly inhibit the lytic activity of the pore-forming protein perforin. A series of analogues were prepared to study structure-activity relationships (SAR) for the this activity, either directly added to cells or released in situ by KHYG-1 NK cells, at non-toxic concentrations. These studies showed that the pyridobenzimidazole moiety was required for effective activity, with strongly basic centres disfavoured. This class of compounds was relatively unaffected by the addition of serum, which was not the case for a previous class of direct inhibitors.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.bmc.2011.05.013 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
UBE2J1 is identified as a novel plasma cell-related gene involved in the prognosis of high-grade serous ovarian cancer.
J Transl Med
January 2025
Department of Gynecology, The Fourth Hospital of Hebei Medical University, No.12 Jiankang Road, Shijiazhuang, 050000, Hebei, China.
Background: Immune cells within tumor tissues play important roles in remodeling the tumor microenvironment, thus affecting tumor progression and the therapeutic response. The current study was designed to identify key markers of plasma cells and explore their role in high-grade serous ovarian cancer (HGSOC).
Methods: We utilized single-cell sequencing data from the Gene Expression Omnibus (GEO) database to identify key immune cell types within HGSOC tissues and to extract related markers via the Seurat package.
Sorafenib enhanced the function of myeloid-derived suppressor cells in hepatocellular carcinoma by facilitating PPARα-mediated fatty acid oxidation.
Mol Cancer
January 2025
Department of Radiation Oncology, Peking University Third Hospital, Beijing, 100191, China.
Background: Sorafenib, an FDA-approved drug for advanced hepatocellular carcinoma (HCC), faces resistance issues, partly due to myeloid-derived suppressor cells (MDSCs) that enhance immunosuppression in the tumor microenvironment (TME).
Methods: Various murine HCC cell lines and MDSCs were used in a series of in vitro and in vivo experiments. These included subcutaneous tumor models, cell viability assays, flow cytometry, immunohistochemistry, and RNA sequencing.
Inhibition of NLRP3 enhances pro-apoptotic effects of FLT3 inhibition in AML.
Cell Commun Signal
January 2025
Department of Biosciences and Medical Biology, Paris-Lodron University Salzburg, Hellbrunner Strasse 34, Salzburg, 5020, Austria.
FLT3 mutations occur in approximately 25% of all acute myeloid leukemia (AML) patients. While several FLT3 inhibitors have received FDA approval, their use is currently limited to combination therapies with chemotherapy, as resistance occurs, and efficacy decreases when the inhibitors are used alone. Given the highly heterogeneous nature of AML, there is an urgent need for novel targeted therapies that address the disease from multiple angles.
View Article and Find Full Text PDFA new NCL-targeting aptamer-drug conjugate as a promising therapy against esophageal cancer.
J Nanobiotechnology
January 2025
School of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, China.
Esophageal cancer (EC) is one of the most common highly malignant tumors of the digestive system, with a poor prognosis under current treatment regimens. Nucleolin (NCL) is overexpressed in many tumors, and drugs specifically targeting NCL may offer a promising strategy for treating esophageal cancer. Here, we designed and prepared a novel aptamer-conjugated drug targeting NCL by AS1411 aptamer-human serum albumin (HSA)-the apoprotein of lidamycin (LDP)-active enediyne chromophore (AE), in order to achieve targeted treatment of esophageal cancer.
View Article and Find Full Text PDFLncRNA-ANRIL regulates CDKN2A to promote malignant proliferation of Kasumi-1 cells.
Cell Div
January 2025
Center for Clinical Laboratories, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou Province, 550004, China.
Objective: This study aimed to investigate the regulatory effects of long non-coding RNA-ANRIL on CDKN2A in the cell cycle of Kasumi-1 cells and elucidate the underlying molecular mechanisms.
Methods: ANRIL and CDKN2A expression levels were quantified using RT-qPCR in peripheral blood samples from acute myeloid leukemia (AML) patients. CDKN2A knockdown efficiency was validated via RT-qPCR, and cell cycle distribution was analyzed using flow cytometry.
Want 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!