Why do Top20 pharmaceutical companies, such as Johnson & Johnson and Pfizer, choose the same technology layout for small molecule new drug research and development?

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In 2017, GSK closed the Shanghai Zhangjiang Neurological Research and Development Center; Lilai Pharmaceutical closed the Shanghai Zhangjiang China Research and Development Center; Novartis closed its cell and gene therapy department in 2016; and Aberwei closed the Nephropathy Research Center in 2015. ... Compared with the prosperity of multinational pharmaceutical enterprises in the past 15 years, the drastic reduction or even closure of their R&D centers and investment resources in China in recent years has caused worries about the prospects of new drug R&D.
According to Deloitte's report released in December 2017, the return on investment in R&D of new drugs in 2017 was only 3.2%, and the cost of a new drug on the market was as high as $1.99 billion.

In addition to the huge R&D investment, the initial patent protection period of compounds is usually very few when new drugs are on the market. If the patent protection period can not even support the peak sales of new drugs, the siege of generic drugs and patent challenges will be faced.
On the premise of guaranteeing the quality of new drugs, how to shorten the research and development cycle and improve the success rate has become a topic of concern to all pharmaceutical professionals. Whether it is cooperation in R&D, IP-VC-CRO, overall outsourcing, or in-depth study of targets, improve screening technology and other means, scientists are actively trying.
In June 2018, AstraZeneca scientists counted 66 new drug discovery articles published in Journal of Medicinal Chemistry from 2016 to 2017 to explore commonly used drug discovery strategies. Five commonly used technologies were summarized, including derivative methods based on known structural compounds, random high-throughput screening, and structure-based methods. Drug design, fragment-based lead compound discovery and DNA coding library screening. Among them, DNA coding compound library technology is one of the emerging technologies in the research and development of new drugs, which has made great progress in the past few years and has been favored by large pharmaceutical enterprises and investors at home and abroad.
It has been reported that AstraZeneca has indicated that the use of DEL technology is one of the reasons to improve its R&D productivity.
The research and application of DNA coding compound library technology, which was included in PubMed database from 1992 to July 2018, has been on the rise since 2012 in academia and industry. Many new drug research and development achievements based on DEL technology, large-scale trading cooperation and DNA coding combination have been carried out. Firms in the repository have also emerged intensively since that time. Large-scale cooperative transactions such as Sanofi's $2.3 billion new drug R&D cooperation with DICE.
From 1992 to 2018, the data of literature classification based on DNA coding compound library technology in PubMed were further collected. Among the pharmaceutical enterprises of Top 20 (ranked by sales in 2016), 19 of them used DNA coding compound library technology to lay out new drug research and development through external cooperation or internal research and development.

Research and Development of Enabling New Drugs by DNA Coding Compound Library Technology

Traditional compound libraries are limited by the high cost of compound synthesis, large storage space requirements, strict screening conditions and high automation requirements. The capacity of compound libraries for screening is often in the order of millions. An important condition for the discovery of lead compounds is the need for a sufficient number of compounds to be screened. Large chemical libraries often require decades of accumulation and substantial and sustained funding. For Chinese companies committed to new drug research and development, it is not the best choice to build a multi-million-level chemical libraries by conventional methods. But scientists have never stopped pursuing a larger chemical space and have focused their attention on the technology of DNA coding compounds library.
The discovery of RIP1 inhibitors is a typical case of the application of DNA coding compounds technology.
At the beginning of the project, GlaxoSmithKline scientist Harris and others used the fluorescence polarization screening method to screen the kinase library containing 40,000 compounds, and high throughput screening technology to screen the library containing 2 million compounds, but no ideal lead compounds were obtained. Finally, 7.7 billion compounds were screened by DNA coding library technology, and a novel compound GSK481, which can specifically bind to RIP1 targets and efficiently block TNF-dependent cellular pathways, was obtained at one time. In the follow-up optimization process, only two atoms of heterocyclic ring were modified and directly entered the clinic. At present, the compound is in phase II clinical research.
Compared with traditional technology, DNA-coded compounds library can not only reach a broader chemical space, but also reduce the cost of synthesis and screening because of the relatively easier requirements for reagents and hardware facilities.

Compared with traditional technology, DEL technology has advantages not only in the quantity and cost of screening compounds, but also in the efficiency and time of screening.
Generally, it takes only a few weeks to synthesize a library of DNA-coding compounds, and only a few months to screen 10 billion-grade compounds, which greatly shortens the discovery cycle of new drugs. In addition, this technology can quickly and efficiently find new structures of compounds for mature targets and avoid low-level duplication; it can screen seedling compounds for targets that are traditionally considered to be difficult to prepare small molecules, such as PPI targets, IL17 targets; it can efficiently find Starting Point for emerging targets, after rapid development. Continuous research provides the possibility to seize the first opportunity in this field.

DNA coding library technology can screen for traditional, challenging and emerging targets and successfully produce high-quality seedling compounds Med. Chem. Commun., 2016, 7, 1898-1909.
China's Strategies to Deal with the Crisis of New Drug Research and Development

DNA coding compound library technology is a highly integrated multi-disciplinary technology platform. At present, X-Chem, Nuevolution and HitGen (Chengdu Pioneer) are the main technologies that can provide large-scale external research and development cooperation of new drugs based on DNA coding compound library.
Among them, as China's first biotechnology company engaged in new drug research and development based on DNA coding compound library technology, since 2015, the company has disclosed 22 new drug research and development partners, many of them with Pfizer, Merchant and other expanding cooperation.

Data sources of Chengdu Pioneer Open Partners (sorted by cooperation time): Chengdu Pioneer Official Website worldwide, according to incomplete statistics of public data such as company websites, since 2015, the number of new drug R&D cooperation based on DNA coding compound library technology has been 64 globally, and Chengdu Pioneer Cooperation accounts for 3 percent. 4.4%, 25% in the U.S. X-Chem and 12.5% in Denmark Nuevolutions.

From 2015 to 2018, the global open cooperative distribution based on DNA coding compound library technology (total number of global open transactions: 64) DNA coding compound library technology can screen high-quality lead compounds that may be missed by other technologies according to the mechanism of a disease, ensuring the breadth of screening, improving the efficiency of screening, and for China. Local biotechnology companies devoted to new drug R&D or traditional pharmaceutical enterprises in transition have laid out new drug R&D solutions in hot or emerging targets with low cost and high efficiency.
Conclusion: Innovation Leads the Future

The fundamental purpose of new drug research and development is to find new molecular entities that can effectively regulate disease targets in the field of diseases that do not meet the treatment needs. Although in the long struggle against diseases, mankind has successfully transformed many malignant diseases into chronic diseases, many chronic diseases have been cured, but the war is far from over, more "stubborn" diseases have been found with the development of science and technology, and become a new threat to the quality of human life.
In the face of new challenges, innovation is imperative.
As the title points out, 19 of Top20 pharmaceutical companies around the world choose to use DNA-coded compound library technology to layout new drug research and development. On the one hand, it proves the great potential of this technology in new drug research and development, on the other hand, it also shows that in the face of severe challenges, even multinational pharmaceutical companies adopt innovative technology for new drug research and development. It is an important means to achieve the strategic objectives of enterprises quickly.