ALK inhibitor / LigaChem Biosci, Korea Research Institute of Chemical Technology - LARVOL DELTA

Development of a TBK1 and ALK dual inhibitor for alleviating depressive behavior via anti-inflammatory effects. (PubMed, Biomed Pharmacother) - "Furthermore, ALS-04 significantly alleviated depressive symptoms, including anhedonia and behavioral despair, in an LPS-induced mouse model of depression. These findings highlight the therapeutic potential of dual TBK1 and ALK inhibition in depression by modulating immune and inflammatory pathways."

Journal • CNS Disorders • Depression • Inflammation • Oncology • Psychiatry • ALK • STING

Design and evaluation of anaplastic lymphoma kinase degraders using a covalent fumarate handle. (PubMed, Bioorg Med Chem Lett) - "In this context, we endeavored to develop ALK degraders utilizing FDA-approved ALK inhibitors-crizotinib, ceritinib, brigatinib, and alectinib-as ALK binders, along with 4-methoxyphenylfumarate as a covalent handle to bind to RNF126 E3 ligase. However, the enhanced anti-proliferative activity of dALK-3 was found to be independent of RNF126, a presumed potential E3 ligase, suggesting the need for investigation of other components within the ubiquitin-proteasome system. Our findings further support the potential application of the fumarate moiety as a binder for E3 ligases in targeted protein degradation."

Journal • Oncology • Targeted Protein Degradation • ALK • EML4

Integrative transcriptomic analysis identifies emetine as a promising candidate for overcoming acquired resistance to ALK inhibitors in lung cancer. (PubMed, Mol Oncol) - "We demonstrated that emetine exhibited effectiveness in inhibiting the growth of ALKi-resistant cells, and further interpreted its impact on the resistant signatures through drug-induced RNA-sequencing data. Our transcriptome-guided systematic approach paves the way for efficient drug discovery to overcome acquired resistance to cancer therapy."

Journal • Preclinical • Lung Cancer • Oncology • Solid Tumor • ALK

DNA methylome and single-cell transcriptome analyses reveal CDA as a potential druggable target for ALK inhibitor-resistant lung cancer therapy. (PubMed, Exp Mol Med) - "In this study, we used an in vitro model of ceritinib-resistant NSCLC and employed genome-wide DNA methylation analysis in combination with single-cell (sc) RNA-seq to identify cytidine deaminase (CDA), a pyrimidine salvage pathway enzyme, as a candidate drug target. Treatment with epigenome-related nucleosides such as 5-formyl-2'-deoxycytidine selectively ablated CDA-overexpressing resistant cells via accumulation of DNA damage. Collectively, our data suggest that targeting CDA metabolism using epigenome-related nucleosides represents a potential new therapeutic strategy for overcoming ALK inhibitor resistance in NSCLC."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK