Hit-to-Lead: Engineering Value Through Precision
The Hit-to-Lead (H2L) phase is where initial screening hits are transformed into optimized lead candidates—compounds with the potential to advance into full-scale development. This transition demands a delicate balance of speed, precision, and innovation: rapidly expanding Structure-Activity Relationships (SAR) while maintaining synthetic control to identify core pharmacophores that maximize potency, selectivity, and developability.
At Oxeltis, we don’t just generate analogs—we strategically engineer value into your chemical series. With 15 years of expertise in medicinal chemistry and custom synthesis, we ensure every compound is optimized for success, securing your chemistry and maximizing your research investment.
01 — Advanced Synthesis Expertise
Cutting-Edge Synthesis for Unmatched Efficiency
Our team—composed of 50% Ph.D. and 50% M.Sc. chemists—deploys advanced chemical technologies to push the boundaries of synthesis. With deep expertise in both academic research and industrial applications, we combine theoretical knowledge and hands-on experience to tackle even the most challenging projects.
From flow chemistry and photochemistry to mechanochemistry and solid-phase peptide synthesis (SPPS), we utilize cutting-edge methodologies to accelerate your program. Supported by state-of-the-art instrumentation, including a high-performance SFC platform for both analytical and preparative purification, we deliver:
Scalable custom synthesis with rapid, high-purity scale-up capabilities of up to 25 grams per day—even for highly complex or chiral mixtures.
Efficiency, precision, and reproducibility at every stage of development.
02 — Lead Optimization Study
Hit-to-Lead Expertise in Action: A Case Study
To demonstrate our capabilities, explore this representative case study involving hit exploration from a DNA-encoded library screening.
01
The Challenge
Our medicinal chemistry team was tasked with refining an initial hit series featuring four points of diversity, with the following objectives:
- Identify the minimal core structure necessary for activity.
- Increase affinity for the target.
- Lower LogP (targeting a range of 0 to 3).
- Increase aqueous solubility (aiming for LogS > -4, or >100 µM).
02
Our Solution
Over 3 months, a dedicated team of 3 FTE chemists deployed advanced synthetic strategies, including:
- AI-supported design: Utilizing a virtual chemical library based on chemical accessibility.
- Diverse chemistry: Implementing solid-supported synthesis, homogeneous catalysis, and cross-coupling reactions.
- Structural innovation: Synthesizing mono/polycyclic, spirocyclic, and bridged moieties.
03
The Results
Through the design and synthesis of 96 targeted compounds, we:
- Confirmed the hit series and established early SAR trends.
- Achieved an average increase in solubility of 2 log units.
- Successfully identified several active compounds with high solubility.
Partner with Oxeltis
Transform your hits into high-potential leads—faster, smarter, and with unmatched precision. With Oxeltis, you gain a partner committed to accelerating your pipeline with scientific rigor and strategic foresight.
