Core Viewpoint - The article discusses a groundbreaking study that utilizes optogenetics to discover compounds that can selectively modulate the Integrated Stress Response (ISR), which has therapeutic potential for various diseases including viral infections, cancer, and neurodegenerative disorders [2][4]. Group 1: Research Overview - The research was published in the journal Cell by a team from the Broad Institute, led by Professor James Collins, and included Felix Wong and Maxwell Wilson [3]. - The study developed an optogenetics platform for drug discovery, enabling the identification of compounds that can selectively eliminate cells with high ISR under various stress conditions [4][14]. Group 2: Methodology and Findings - The research team utilized double-stranded RNA-dependent protein kinase R (PKR) as a key sensor for ISR activation, simulating natural activation during viral infections [7]. - A high-throughput screening of 370,830 compounds was conducted, identifying those that enhance cell death without cytotoxicity across different cell types and stressors [7][14]. - The identified compounds were shown to upregulate Activating Transcription Factor 4 (ATF4), increasing cellular sensitivity to stress and apoptosis, with GCN2 identified as a molecular target [8]. Group 3: Antiviral Activity - The compounds demonstrated broad-spectrum antiviral activity, with one compound significantly reducing viral load in a mouse model of herpes simplex virus infection [9][14]. - Structure-activity relationship and toxicology studies highlighted opportunities for optimizing therapeutic effects [9]. Group 4: Significance of the Study - The study showcases a novel optogenetics approach for drug discovery and introduces ISR enhancers with potential therapeutic applications [10].

Core Insights - Chengdu Xian Dao's revenue for 2024 reached 427 million yuan, marking a year-on-year growth of 14.99%, achieving a historical high [1] - The company's net profit attributable to shareholders, excluding non-recurring gains and losses, surged by 1563.94% to 57.44 million yuan [1] - In Q1 2025, the company maintained a robust growth trajectory with revenue of 107 million yuan and a net profit of 17.51 million yuan, reflecting a year-on-year increase of 113.63% [1] Business Performance - The DEL (DNA-encoded library) segment, a cornerstone of the company, generated approximately 200 million yuan in revenue, up 8.55% year-on-year, solidifying its industry-leading position [1] - The drug design business, benefiting from milestone revenue recognition from the UK subsidiary Vernalis, reported revenue of about 120 million yuan, a 30.99% increase [1][2] - The delivery molecule commercialization project achieved a breakthrough in revenue conversion, generating 48.03 million yuan, a 39.72% increase [2] - Chemical services and biological services segments reported revenues of 17.07 million yuan and 18.37 million yuan, reflecting year-on-year growth of 8.09% and 15.71% respectively [2] R&D Investment - In 2024, the company invested 67.33 million yuan in R&D, accounting for 15.77% of its revenue, and secured 32 authorized invention patents while submitting 27 new patent applications [3] - The company published 8 scientific papers in core industry journals and 5 peer-reviewed papers, indicating a continuous enhancement of its technological innovation and academic contributions [3] - The self-developed drug pipeline, HG146, officially entered clinical phase II by the end of 2024, showcasing the company's commitment to advancing its proprietary research [3] Strategic Positioning - The establishment of the first global DEL alliance with major international pharmaceutical companies aims to share resources and accelerate drug discovery [2] - The company has built a "technology moat + financial stability + strategic foresight" framework, demonstrating resilience and growth potential in the biopharmaceutical sector [4] - The explosive growth in 2024 and Q1 2025 is attributed to the commercialization breakthroughs of core technology platforms and strategic ecological layout [4]