In this technique, phosphatidylserine (PS 1 2), which is abundantly expressed in tumor site, is used as a significant target molecule to combine drugs to fight cancer. After more than four years, with the support of the Ministry of Economic Affairs, the R&D team successfully developed a new anticancer drug DBPR 186, which is a candidate drug for the transmission system (DM- 1) developed in August this year (2020).
The compound delivers the anticancer drug DM- 1 to tumor tissues and tumor tissues, and releases DM- 1 after combining with high-concentration PS, which can increase the drug concentration in tumors, enhance the anticancer efficacy, and greatly reduce the side effects of drugs. In addition to the above characteristics, the delivery system of dimethyl pyridine amine derivatives has another bright spot, that is, the delivered drugs can once again enhance the recognition of PS signals, so that the ability of the delivery system to find signals can be doubled, thus optimizing the therapeutic effect.
The research team of anti-cancer drug delivery system in the Institute of Biotechnology and Medicine of our hospital includes four laboratories: medicinal chemistry, molecular biology, pharmacokinetics and animal drug toxicology. Each laboratory carries out different tasks in stages, and jointly produces a new candidate drug DBPR 186 with development potential and patent. The first is the research team of medicinal chemistry (Pan Peiyun, Lai, Wu Weiting, Liu, etc. ), associate researcher Zou Lun, has been trying to synthesize more than 20 kinds of dimethyl pyridine amine derivatives modified by specific functional groups.
The evaluation of surface plasmon resonance (SPR) and the confirmation of Xu Research Laboratory show that the derivatives of dimethyl pyridine amine can effectively increase the binding capacity with PS. The research team of medicinal chemistry combined it with anti-cancer drug DM- 1 to synthesize more than 90 complexes, and optimized the hydrophilicity of the drug delivery system through the linker, which improved the efficiency of the complexes in vivo. The pharmacokinetic test of the synthetic complex was conducted by Associate Professor Ye's laboratory. At the same time, the research team of medicinal chemistry also designed a new linker to combine with DM- 1, which improved the pharmacokinetic stability of the complex and delivered DM- 1 to tumor tissue. After binding with PS, the linker breaks and the anticancer drug DM- 1 is released.
Immediately afterwards, the laboratory team of researcher Jidong Chen (Dr. Qiu, Dr. Xu Jiayu and several research assistants) took over the animal pharmacology and toxicity test. The animal test results of triple negative breast cancer (HCC 1806) showed that DBPR 186(3 mg/Kg, once a week 1 time, lasting for 3 weeks) could make breast cancer large.
At present, the patent layout of DBPR 186 has been carried out. And cooperated with domestic pharmaceutical companies to achieve the phased goal of continuing intellectual property rights and creating product value. In this study, the research and development strategy of new drugs and quasi-new drugs is adopted, and the integrated technical team of the Institute of Biotechnology and Drugs of our hospital is used to carry out drug research and development, so as to provide high-quality technical sources for the domestic biotechnology pharmaceutical industry, and hope that the research results with industrial development potential will be transferred to domestic and foreign biotechnology pharmaceutical companies as soon as possible, and the new drug technologies and products developed in China will be introduced to the international market, so as to achieve the ultimate goal of benefiting patients.