The optimization of screening hits on a promising new target for therapy of certain cancers involving anaplastic lymphoma kinase (ALK) inspired the development of this efficient solid-phase chemistry. A series of novel pyridones have been recently discovered as inhibitors of ALK, which led to the design of focused libraries around the pyridone scaffold. A stepwise process involving iterative template modification based on both medicinal chemistry insights and computational ranking of virtual libraries was employed in the design. The unique solid-phase chemistry has addressed the need for rapid optimization of this "early lead" series. Herein the methodology and scope of the chemistry, as well as its application for library synthesis, are discussed.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1021/cc060018r | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Coexistence of a novel , double-fusion in a lung poorly differentiated adenocarcinoma patient and response to alectinib: a case report and literature review.
Front Oncol
December 2024
Department of Pathology, China-Janpan Friendship Hospital, Beijing, China.
Background: Anaplastic lymphoma kinase () rearrangement, the most common oncogenic rearrangement in lung adenocarcinoma, occurs in approximately 5% of non-small cell lung cancer (NSCLC) patients. gene is the most common partner of rearrangement, and distinct EML4-ALK fusions differ in their responsiveness to ALK tyrosine kinase inhibitors. However, the concurrence of two rearrangements in one patient and whose response to ALK-TKIs have rarely been reported so far.
View Article and Find Full Text PDFAnalysis of outcomes in resected early-stage NSCLC with rare targetable driver mutations.
Ther Adv Med Oncol
December 2024
Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre (PMCC), University Health Network (UHN), 700 University Avenue, 7-812, Toronto, ON M5G 2M9, Canada.
Background: Given advancements in adjuvant treatments for non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK)-targeted therapies, it is important to consider postoperative targeted therapies for other early-stage oncogene-addicted NSCLC. Exploring baseline outcomes for early-stage NSCLC with these rare mutations is crucial.
Objectives: This study aims to assess relapse-free survival (RFS) and overall survival (OS) in patients with resected early-stage NSCLC with rare targetable driver mutations.
Astrocyte-derived PTN alleviates deficits in hippocampal neurogenesis and cognition in models of multiple sclerosis.
Stem Cell Reports
December 2024
Department of Neurology, The Third Affiliated Hospital of Sun Yat-Sen University, 600 Tianhe Road, Guangzhou 510630, Guangdong Province, China. Electronic address:
Multiple sclerosis (MS) is an autoimmune inflammatory demyelinating disease that results in motor, sensory, cognitive, and affective deficits. Hippocampal demyelination, a common occurrence in MS, is linked to impaired cognitive function and mood. Despite this, the precise mechanisms underlying cognitive impairments in MS remain elusive.
View Article and Find Full Text PDFA Phase I Study of Romidepsin in Combination With Gemcitabine, Oxaliplatin, and Dexamethasone in Patients With Relapsed or Refractory Aggressive Lymphomas Enriched for T-Cell Lymphomas.
Clin Lymphoma Myeloma Leuk
December 2024
Division of Medical Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO. Electronic address:
Introduction: Histone deacetylase inhibitors (HDACi) and combination chemotherapy are independently used to treat relapsed/refractory (R/R) lymphoma. In vitro studies suggest that the addition of HDACi to platinum-based chemotherapy is synergistic.
Patients And Methods: We conducted a phase I study of romidepsin, gemcitabine, oxaliplatin and dexamethasone (Romi-GemOxD) in R/R aggressive lymphomas with an expansion cohort in T-cell lymphomas.
Proliferative Myositis of the Breast in a Patient with Contralateral Phyllodes Tumor: A Unique Pseudomalignant Lesion.
Ann Ital Chir
December 2024
Department of Pathology, Bakirkoy Dr. Sadi Konuk Education and Research Hospital, 34147 İstanbul, Türkiye.
Aim: We report a case of proliferative myositis (PM) of the breast, which is the second reported in the English literature.
Case Presentation: A 49-year-old woman underwent surgery due to a fibroadenoma in the right and phyllodes tumor in the left breast. One month after these surgeries, a right breast mass rapidly grew at the surgical site, and biopsy did not provide a diagnosis.
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!