The MLK1-3 activity for a series of analogues of the indolocarbazole K-252a is reported. Addition of 3,9-bis-alkylthiomethyl groups to K-252a results in potent and selective MLK inhibitors. The in vitro and in vivo survival promoting activity of bis-isopropylthiomethyl-K-252a (16, CEP-11004/KT-8138) is reported.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/s0960-894x(01)00690-4 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
[Blinatumomab-based combination treatment for CD19-positive acute leukemia of an ambiguous lineage].
Zhonghua Xue Ye Xue Za Zhi
November 2024
The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, National Clinical Research Center for Hematologic Diseases, Key Laboratory of Thrombosis and Hemostasis Under Ministry of Health, Suzhou 215006, China.
Acute leukemia of ambiguous lineage (ALAL) is a rare type of acute leukemia and is extremely difficult to treat. Here, we present six patients with CD19-positive ALAL who were successfully treated with blinatumomab-based combination treatment in the front-line setting. Five were diagnosed with B-cell/myeloid mixed phenotype acute leukemia (MPAL) and one with B-cell/T cell MPAL.
View Article and Find Full Text PDFAn inflammatory state defines a high-risk T-lineage acute lymphoblastic leukemia subgroup.
Sci Transl Med
January 2025
Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2C4, Canada.
T-lineage acute lymphoblastic leukemia (ALL) is an aggressive cancer comprising diverse subtypes that are challenging to stratify using conventional immunophenotyping. To gain insights into subset-specific therapeutic vulnerabilities, we performed an integrative multiomics analysis of bone marrow samples from newly diagnosed T cell ALL, early T cell precursor ALL, and T/myeloid mixed phenotype acute leukemia. Leveraging cellular indexing of transcriptomes and epitopes in conjunction with T cell receptor sequencing, we identified a subset of patient samples characterized by activation of inflammatory and stem gene programs.
View Article and Find Full Text PDFVPO1 Promotes Programmed Necrosis of Cardiomyocytes in Rats with Chronic Heart Failure by Upregulating CYLD.
Front Biosci (Landmark Ed)
December 2024
Department of Cardiovascular Medicine, The Affiliated Changsha Hospital of Xiangya School of Medicine, Central South University, 410008 Changsha, Hunan, China.
Background: Chronic heart failure (CHF) is a serious cardiovascular condition. Vascular peroxidase 1 (VPO1) is associated with various cardiovascular diseases, yet its role in CHF remains unclear. This research aims to explore the involvement of VPO1 in CHF.
View Article and Find Full Text PDFProtein shapeshifting in necroptotic cell death signaling.
Trends Biochem Sci
December 2024
Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3052, Australia; Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, Australia. Electronic address:
Necroptosis is a mode of programmed cell death executed by the mixed lineage kinase domain-like (MLKL) pseudokinase following its activation by the upstream receptor-interacting protein kinase-3 (RIPK3), subsequent to activation of death, Toll-like, and pathogen receptors. The pathway originates in innate immunity, although interest has surged in therapeutically targeting necroptosis owing to its dysregulation in inflammatory diseases. Here, we explore how protein conformation and higher order assembly of the pathway effectors - Z-DNA-binding protein-1 (ZBP1), RIPK1, RIPK3, and MLKL - can be modulated by post-translational modifications, such as phosphorylation, ubiquitylation, and lipidation, and intermolecular interactions to tune activities and modulate necroptotic signaling flux.
View Article and Find Full Text PDFAn intracellular bacterial pathogen triggers RIG-I/MDA5-dependent necroptosis.
Curr Res Microb Sci
November 2024
CAS and Shandong Province Key Laboratory of Experimental Marine Biology, Institute of Oceanology; CAS Center for Ocean Mega-Science, Chinese Academy of Sciences, Qingdao, China.
RIG-I and MDA5 are members of RIG-I-like receptors (RLRs) that detect viral RNA within the cytoplasm and subsequently initiate antiviral immune responses. Necroptosis is a form of programmed cell death (PCD) executed by mixed lineage kinase domain-like (MLKL), which, upon phosphorylation by receptor-interacting protein kinase 3 (RIPK3), causes necrotic cell death. To date, no link between RLRs and necroptosis has been observed during bacterial infection.
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!