Unlocking the potential of DEL | Inspire Hit Discovery

March 4, 2020 – By going commercial, DNA Encoded Library (DEL) technology facilitates rapid discovery and provides access to more chemical entities at lower cost. Over the years, DEL has become a disruptive drug discovery technology in comparison to traditional high-throughput screening (HTS) where it allows expedition of early stage drug discovery. However, DEL platforms don’t succeed in isolation, as they depend on upstream and downstream activities. To create the best hit generating engine, the entire process must be optimized from target acquisition to follow-up confirmation assays. Additionally, structural information acquired through crystallography can be necessary to turn a hit molecule into a lead series.

WuXi AppTec has recently launched the HitS (Hit Success) business unit to integrate upstream and downstream technologies of DEL to better empower the early stage drug discovery process. WuXi’s goal is to boost R&D productivity by providing more and better hit molecules, and helping to set the stage for follow-up Med-Chem optimization. To find out more about this new initiative, we interviewed Dr. Xuanjia Peng, head of the HitS business unit of WuXi AppTec.

Why HitS? Starting with DEL…

Talking about why the HitS (Hit Success) division was established, Dr. Xuanjia Peng said: “This is back to the mission of WuXi AppTec: to continue strengthening our open-access capability and technology platforms to enable anyone and any company to discover and develop pharmaceuticals and healthcare products to benefit patients. As part of this mission, HitS was created to provide comprehensive hit discovery services of the highest quality, short timelines, and lower costs to benefit both pharmaceutical companies/institutes and the patients they serve.

As one of the core strength in the integrated HitS business unit, WuXi DNA-Encoded Library platform (WuXi DEL) has constructed DEL libraries with more than 90 billion synthetic compounds and also offers tailored DEL services including library production and affinity screening services to global customers. By combining combinatorial chemistry and affinity screening with next generation sequencing technologies, DEL technology can shorten the usual screening time of several months to just 4 weeks, realizing the vision of accelerating the process of hit discovery.

However, a complete DEL screening can still be too expensive for some researchers. “We are working on ways to reduce the cost of DEL services to lower the threshold of drug discovery and to improve the efficiency of early stage research. For instance, as one of the main contributors, the open source DELopen platform facilitates hit discovery for academic targets. In addition, we have launched the affordable DELight option to entice a wider DEL market.” said Dr. Xuanjia Peng.

Compared to traditional DEL services, DELight is a more convenient, efficient and economical service package, allowing researchers to perform their own affinity selection with minimum assay development and without disclosing target information. “We have selected more than 14 billion compounds from our 90 billion DEL pool to be included in this DELight kit for early drug discovery.”, said Dr. Peng. “Now that our DEL services are underway for startups and smaller institutes, we are starting to think bigger about how we can do it even better.”

Empowering DEL: from protein science to biophysical technology

“After communicating with DEL customers for the last 2 years, we have noticed that our DEL clients faced challenges in acquiring qualified target proteins for DEL screens. Many of our clients are interested in “first-in-class” targets that needs special design and optimization to become suitable for DEL condition settings and screens.” Dr. Peng said. Hence by integrating WuXi AppTec’s related capabilities in protein expression with DEL screening helps break through the problem of protein acquisition and quality assessment. More importantly, a tailored protein production proposal prior to screening ensures that the protein is the optimal construct.

Furthermore, the integrated HitS platform aims to provide the client with a clearer picture of the mechanism of actions (MOA) of the lead compound with the target. As pointed out by Dr. Xuanjia Peng, hit compounds from previous DEL screens were often directly assayed biochemically to determine their inhibitory effects and no thorough understanding in the interaction between the compound and the target protein was conducted. Lack of biophysical studies has impeded the success rate of downstream lead optimization and development. The integration of biophysical assays, crystallography and DEL screening will better able the validation of the binding activity of selected hit compounds and help the client to proceed with Med-Chem SAR.

“The big idea here is that clients will only need to provide us with the name of the target and the HitS team will provide a one-stop solution from target acquisition, to compound screening, to target-compound interaction studies. We are looking forward to further accelerate the process and solve the pain points for clients during the drug discovery by the technical integration and business model innovation of HitS.”

The future of HitS

The establishment of HitS enables companies in the pharmaceutical, biotech and health care industries worldwide to advance the productivity of the new drug discovery. “It is likely that the future drug discovery can be accelerated by in silico efforts”, Dr. Peng is very excited. “At that point, the early-stage development of drug discovery will no longer be limited by funding or capacity. Here at HitS, we are committed in building the most advanced technology platform in the drug discovery industry to fulfill our vision that ‘every drug can be made and every disease can be treated’.”

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