Unlocking Molecular Potential: The Evolution of Topliss Tree and Bioisosteric Strategies in Modern Drug Discovery

Unlocking Molecular Potential: The Evolution of Topliss Tree and Bioisosteric Strategies in Modern Drug Discovery Systematic Optimization Foundation: The Topliss tree methodology established fundamental principles for systematic molecular optimization that remain relevant in modern computational drug design approaches Bioisosteric Strategy Evolution: Classical bioisosterism has expanded to encompass sophisticated replacements addressing multiple optimization parameters simultaneously, from […]

JAK2-V617F and the Evolution of Targeted Therapy: Precision Medicine Transforms Myeloproliferative Neoplasm Treatment

JAK2-V617F and the Evolution of Targeted Therapy: Precision Medicine Transforms Myeloproliferative Neoplasm Treatment https://www.marcdeller.com/wp-content/uploads/2025/09/v617f_540p.mp4 Link to JAK2-V617F Poster Link to Clinical Trial Mutation-Specific Targeting: JAK2-V617F occurs in 95% of polycythemia vera cases, driving development of selective inhibitors with enhanced mutant protein affinity Combination Synergy: Pelabresib plus ruxolitinib achieved 65% spleen reduction in 2024 trials, demonstrating […]

Building a Comprehensive Protein Production, X-ray Crystallography, and Cryo-EM Laboratory from Scratch

Building a Comprehensive Protein Production, X-ray Crystallography, and Cryo-EM Laboratory from Scratch https://www.marcdeller.com/wp-content/uploads/2025/09/glacios_540p.mp4 Infrastructure Integration: Seamless workflow design connecting protein production through structural determination requires comprehensive planning and standardized protocols that maximize efficiency while maintaining quality control across all platforms Automation Excellence: Implementation of AI-driven crystallization screening and automated vitrification systems dramatically reduces manual intervention […]

Imidaz0[1,2-a]pyrimidine-5(1 h)-ones having a covalent warhead at the 3-position as wrn inhibitors

Imidaz0[1,2-a]pyrimidine-5(1 h)-ones Having a Covalent Warhead at the 3-Position as WRN Inhibitors Link to Google Patent Synthetic Lethality Mechanism: WRN inhibitors exploit the dependency of MSI-H cancer cells on Werner helicase for survival, inducing selective DNA damage and apoptosis while sparing microsatellite-stable cells Covalent Warhead Strategy: The 3-position covalent warhead design enables irreversible binding to […]

Imidaz0[1,2-a]pyrimidine-5(1 h)-ones as wrn inhibitors

Imidaz0[1,2-a]pyrimidine-5(1 h)-ones as WRN Inhibitors Link to Google Patent Selective Targeting: Imidazo[1,2-a]pyrimidine-5(1H)-ones demonstrate exceptional selectivity for MSI-high cancer cells while sparing normal tissues Mechanistic Innovation: WRN helicase inhibition represents a novel synthetic lethal approach distinct from traditional DNA damage agents Clinical Promise: Multiple WRN inhibitors have entered clinical trials with encouraging early efficacy signals in […]

Advancing Precision Oncology: A Deep Dive into Four Breakthrough Targeted Therapies Transforming Cancer Treatment

Advancing Precision Oncology: A Deep Dive into Four Breakthrough Targeted Therapies Transforming Cancer Treatment Link to KRAS-G12D Trial (INCB161734) Link toJAK2-V617F Trial (INCB160058) Link to anti-CALR antibody Trial (INCA033989) Link to CDK2 Trial (INCB123667) Mutation-Selective Targeting: INCB161734 achieves over 80-fold selectivity for KRAS-G12D versus wild-type KRAS, demonstrating unprecedented precision in oncogenic mutation targeting Immunological Elimination: […]

Call Me A Jerk: Persuading AI to Comply with Objectionable Requests

Call Me A Jerk: Persuading AI to Comply with Objectionable Requests Link to Paper Persuasive Vulnerability: AI systems designed to be helpful and conversational inherit human-like susceptibility to social engineering attacks, achieving 92%+ success rates against advanced models Systematic Exploitation: A comprehensive taxonomy of 40 persuasion techniques from social science research enables automated generation of […]

Approaches to automated protein crystal harvesting

Approaches to automated protein crystal harvesting Link to Paper Precision Robotics: Six-axis anthropomorphic robots achieve submicron positioning accuracy for crystals as small as 10 micrometers Smart Microgrippers: MEMS-fabricated tools provide controlled pressure application while enabling direct X-ray data collection Acoustic Processing: Non-contact ejection systems operate at hundreds of droplets per second for high-throughput applications AI […]

Crystal structure of a two-subunit TrkA octameric gating ring assembly

Crystal structure of a two-subunit TrkA octameric gating ring assembly Link to Paper Ancient Architecture Revealed: The two-subunit TrkA system represents an evolutionary precursor to modern single-subunit potassium transporters, offering insights into protein evolution Sophisticated Regulation: The octameric assembly employs multiple nucleotide binding sites and allosteric networks to achieve precise control over potassium transport Thermophilic […]