Next-Generation antibody drug conjugates. Expert insights into the scientific strategies shaping the future of ADC development. Developing successful antibody drug conjugates (ADCs) is becoming increasingly complex. Advances in payload design, linker chemistry, target selection and conjugation technologies are creating new opportunities, while introducing new scientific and development challenges. To help navigate this evolving landscape, Sygnature Discovery has developed this eBook, bringing together insights from 14 ADC experts at Sygnature Discovery on the strategies, technologies and emerging trends shaping the next generation of ADC development. In the eBook, you'll learn: Why payload optimization is becoming a key driver of ADC innovation and therapeutic differentiation How integrated design across antibodies, linkers, payloads and conjugation strategies can improve development outcomes The role of linker technologies in balancing stability, payload release, efficacy and safety Key considerations for target selection, antigen biology and effective antigen-payload combinations How analytical characterization, pharmacology and translational strategies support better development decisions Emerging innovations including dual-payload ADCs, novel conjugation approaches and degrader-antibody conjugates (DACs) Gain practical insights from ADC experts on the scientific strategies, technologies and innovations shaping the future of antibody-drug conjugate discovery. Ready to explore the future of ADC development? Download your copy of the eBook Meet the experts. This eBook brings together perspectives from 14 experts across medicinal chemistry, protein sciences, structural biology, bioinformatics, pharmacology and DMPK.

Supporting k[v]7 drug discovery: spotlight k[v]7.2/7.3. Why kv7.2/7.3 matters. The K[V] 7.2/7.3 (KCNQ2/KCNQ3) channel complex plays a critical role in regulating neuronal excitability through generation of the neuronal M-current. By limiting repetitive neuronal firing and helping to stabilize membrane potential, these channels are important regulators of normal neuronal signaling. Interest in K[V] 7-targeted therapeutics has grown due to increasing understanding of the role these channels play in disorders associated with neuronal hyperexcitability, including epilepsy, developmental and epileptic encephalopathies (DEEs), KCNQ2-related disorders and neuropathic pain. As a result, robust pharmacological tools are required to support the discovery and characterization of novel K[V] 7 modulators. Enabling reliable characterization of K[V] 7.2/7.3 modulators. At Sygnature Discovery, Sygnature Discovery has established a K[V] 7.2/7.3 assay designed to support the characterization of compounds targeting this channel complex. The assay captures both channel activation and inhibition, enabling comprehensive assessment of compound activity. Beyond assay performance, successful ion channel drug discovery often requires complementary technologies that support screening, characterization and translational research. Sygnature Discovery combine automated electrophysiology, for high-throughput screening and profiling, with manual patch clamp studies that provide gold-standard kinetic and mechanistic insights. These capabilities can be integrated with advanced cellular models and custom assay development to support a broad range of research objectives. For discovery teams working in ion channel research, the ability to confidently detect multiple modes of pharmacology is essential for compound profiling, mechanism-of-action studies and Structure-Activity Relationship (SAR) investigations. Through the detection of both channel activation and inhibition, its K[V] 7.2/7.3 assay provides a robust platform for the pharmacological characterization of K[V] 7 modulators. Demonstrating agonist and antagonist pharmacology. To evaluate assay suitability, reference modulators were assessed in both agonist and antagonist assay formats. Concentration-response studies with the K[V] 7.2/7.3 activator ML-213 and inhibitor ML-252 demonstrated clear, concentration-dependent modulation of channel activity (Figure 1). Reproducibility to support drug discovery campaigns. To assess longer-term assay robustness, K[V] 7.2/7.3 performance was evaluated across five separate days (Figure 2). These studies demonstrated consistent assay behavior and reproducible pharmacological responses over time. Long-term stability studies indicate consistent assay performance suitable for SAR-driven optimization. Want to discuss its K[V] 7.2/7.3 pharmacology capabilities and broader ion channel expertise?

Recombinant Factor C vs LAL: A more sustainable approach to endotoxin testing. Advancing endotoxin detection through recombinant Factor C technology. Innovative approaches that improve outcomes and support more sustainable laboratory practices are becoming increasingly important across drug discovery. At Sygnature Discovery's Protein Science division, Sygnature Discovery has recently implemented a recombinant Factor C (rFC)-based endotoxin detection assay that delivers robust analytical performance while reducing reliance on horseshoe crab-derived reagents. Endotoxins are lipopolysaccharide (LPS) components of the outer membrane of Gram-negative bacteria such as E. coli. These molecules are released as bacteria grow and die and can trigger a strong inflammatory response in humans. Excessive exposure may lead to septic shock and organ failure, making accurate endotoxin detection essential for pharmaceuticals, biologics, vaccines, medical devices and research materials that may come into contact with the body. Endotoxin contamination can also affect cell-based, in vivo and in vitro studies, potentially compromising experimental outcomes and data quality. The horseshoe crab (Limulus polyphemus) can be described as a living fossil. This species has survived for more than 450 million years and possesses a unique immune defence mechanism. Amoebocytes in horseshoe crab blood detect bacterial invasion and trigger a highly sensitive clotting response (Figure 1). This defence mechanism evolved because, unlike warm-blooded animals, horseshoe crabs cannot raise their body temperature to combat infection. The clotting cascade begins when LPS endotoxins bind to Factor C, initiating a serine protease pathway that ultimately forms a protective clot around the invading bacteria. Harm of harvesting horseshoe crabs. During the 1960s, researchers recognized the potential of this clotting mechanism as a highly sensitive method for detecting bacterial endotoxins. This led to the development of the Limulus amoebocyte lysate (LAL) assay, which was approved by the FDA in 1977 and remains the primary method for testing parenteral drugs, vaccines, intravenous fluids and many implanted medical devices. The LAL assay represented a significant advance over earlier animal-based pyrogen tests and has become one of the most important tools for ensuring product safety. For decades the LAL test has made use of the Factor C pathway (Figure1) to detect endotoxin contamination using a qualitative gel clot. Although Sygnature Discovery has moved onto a quantitative method, LAL remains the key ingredient and is generated by bleeding live horseshoe crabs. Crab bleeding is estimated to cause 70,000 horseshoe crab deaths per year in the USA [1], as many crabs do not survive the bleeding process (10-30%), and the long-term effects on those that do are poorly understood. Harvesting of horseshoe crabs for biomedical applications has raised concerns about the long-term sustainability of some populations and the wider ecological impact on species that depend upon them. Horseshoe crab eggs are a crucial food source for many species, including the red knot shorebird, which undertakes an annual 19,000-mile migration [2]. A recombinant alternative. Accurate endotoxin measurement is a critical component of many protein production, characterization and downstream application workflows at Sygnature Discovery. Its Protein Science team routinely works to minimize endotoxin contamination through carefully controlled purification processes and robust analytical testing, helping to ensure that client materials are suitable for downstream research applications. Within the Protein Science department, Sygnature Discovery has been trialling a new endotoxin detection test based on recombinant Factor C (rFC) and a small fluorescent peptide. By switching to this recombinant Factor C alternative, Sygnature Discovery is helping to reduce the number of live crabs that need to be bled, aligning with its commitment to more environmentally friendly practices. Sygnature Discovery has carried out internal experiments to ensure that it gives comparable results to previously used LAL assay. Beyond reducing reliance on animal-derived reagents, the rFC assay offers several scientific and practical advantages. The measurable range of endotoxin concentrations is substantially wider, from 0.05 EU/mL to 50 EU/mL, compared with 0.1 EU/mL to 1 EU/mL using its previous method. The assay also requires less sample material, is quicker to perform and provides more reliable standard curve generation (Figure 2 and 3). The graphs above show the old (endogenous Factor C) and new (rFC alternative) standard curves. The new standard curve is plotted on a logarithmic scale, this illustrates the wider range of endotoxin concentrations that are detectable with this kit. Conclusion - better data and happier crabs. Its evaluation of recombinant Factor C technology demonstrated performance comparable to traditional LAL-based methods while delivering a number of operational and analytical advantages. By transitioning to an rFC-based assay, Sygnature Discovery continues to combine scientific rigour with responsible laboratory practices. The adoption of rFC technology enables Sygnature Discovery to generate high-quality endotoxin data for its clients while reducing dependence on horseshoe crab-derived reagents. It is a practical example of how innovation can support both scientific excellence and more sustainable approaches to drug discovery.