A series of hybrid compounds of bestatin (1) and actinonin (3), which promote degradation of cellular inhibitor of apoptosis protein 1 (cIAP1), were designed and synthesized. Structure-activity relationship studies indicated that absolute configuration, hydrophobicity at the alpha-position of the internal amide carbonyl group, and the presence of a small substituent at the alpha-position of the ester group are important factors for the expression of potent cIAP1 degradation-promoting activity. HAB-5A (30b) showed the most potent activity (IC(50)=0.53 microM) among the compounds prepared.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.bmc.2008.02.024 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
The role of the NOTCH1 signaling pathway in the maintenance of mesenchymal stem cell stemness and chondrocyte differentiation and its potential in the treatment of osteoarthritis.
J Orthop Surg Res
January 2025
Department of Knee Surgery, The First Hospital of Hebei Medical University, Hebei, China.
Objective: This study aims to explore the potential role of mesenchymal stem cells (MSCs) in the treatment of osteoarthritis (OA), particularly the function of the NOTCH1 signaling pathway in maintaining the stemness of MSCs and in chondrocyte differentiation.
Methods: Utilizing diverse analytical techniques on an osteoarthritis dataset, we unveil distinct gene expression patterns and regulatory relationships, shedding light on potential mechanisms underlying the disease. Techniques used include the culture of MSCs, induction of differentiation into chondrocytes, establishment of stable cell lines, Western Blot, and immunofluorescence.
CYP3A5 promotes glioblastoma stemness and chemoresistance through fine-tuning NAD/NADH ratio.
J Exp Clin Cancer Res
January 2025
School of Medicine, Chinese PLA General Hospital, Nankai University, Beijing, China.
Background: Glioblastoma multiforme (GBM) exhibits a cellular hierarchy with a subpopulation of stem-like cells known as glioblastoma stem cells (GSCs) that drive tumor growth and contribute to treatment resistance. NAD(H) emerges as a crucial factor influencing GSC maintenance through its involvement in diverse biological processes, including mitochondrial fitness and DNA damage repair. However, how GSCs leverage metabolic adaptation to obtain survival advantage remains elusive.
View Article and Find Full Text PDFCrisdesalazine alleviates inflammation in an experimental autoimmune encephalomyelitis multiple sclerosis mouse model by regulating the immune system.
BMC Neurosci
January 2025
Laboratory of Veterinary Internal Medicine, Department of Clinical Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul, 08826, Republic of Korea.
Microglia/macrophages participate in the development of and recovery from experimental autoimmune encephalomyelitis (EAE), and the macrophage M1 (pro-inflammatory)/M2 (anti-inflammatory) phase transition is involved in EAE disease progression. We evaluated the efficacy of crisdesalazine (a novel microsomal prostaglandin E2 synthase-1 inhibitor) in an EAE model, including its immune-regulating potency in lipopolysaccharide-stimulated macrophages, and its neuroprotective effects in a macrophage-neuronal co-culture system. Crisdesalazine significantly alleviated clinical symptoms, inhibited inflammatory cell infiltration and demyelination in the spinal cord, and altered the phase of microglial/macrophage and regulatory T cells.
View Article and Find Full Text PDFPNMA1 is a novel immune modulator and therapeutic target in hepatocellular carcinoma linked to bile acid metabolism.
Sci Rep
January 2025
Department of Breast Surgery, China-Japan Union Hospital of Jilin University, Changchun, 130033, China.
Hepatocellular carcinoma (HCC) necessitates innovative prognostic biomarkers and therapeutic targets. By investigating PNMA1 in HCC via the TCGA and GEO databases and our clinical data, we found that its overexpression is associated with worse survival. The relevance of PNMA1 extends to immune factors such as M1 macrophages, CD8 T cells, and immune checkpoints.
View Article and Find Full Text PDFCinnamic acid conjugated with triazole acetamides as anti-Alzheimer and anti-melanogenesis candidates: an in vitro and in silico study.
Sci Rep
January 2025
Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
In this study, new cinnamic acid linked to triazole acetamide derivatives was synthesized and evaluated for anti-Alzheimer and anti-melanogenesis activities. The structural elucidation of all analogs was performed using different analytical techniques, including H-NMR, C-NMR, mass spectrometry, and IR spectroscopy. The synthesized compounds were assessed in vitro for their inhibitory activities against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and tyrosinase enzymes.
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!