Chinese Academy of Medical Sciences & Peking Union Medical College

RESEARCH

Department of Drug Metabolism

Department of Drug Metabolism is specialized in pre-clinical pharmacokinetics of new drugs and related basic research. The department currently has 23 professional researchers and graduate students, including 4 research fellows, 1 associate research fellow, 2 doctoral supervisors, 3 master's supervisors. In recent years, it has undertaken a number of major national or provincial fund projects such as "863 Program", "973 Program", "The Eleventh Five-Year Plan", "The Twelfth Five-Year Plan", the National Natural Science Foundation of China and Beijing Drug Metabolism Platform.

Main research interests:

1) Research and application of key technology of interaction between intestinal bacteria and drugs;

2) Key techniques and in vivo metabolic characteristics of polypeptide probe for early diagnosis of colorectal cancer;

3) Mechanism research of relationship between intestinal bacteria and clinical chronic disease and personalized treatment;

4) Evaluation of early pharmacokinetic properties of candidate drugs, pre-clinical pharmacokinetics of new drugs (Toxicokinetics), regulation and molecular mechanism of drug metabolism enzymes and transport proteins, etc.

Principal Investigators

PK/PD study of anti-cerebral ischemia agentEarly pharmacokinetic studies showed that the brain protectant IMM-H004 was eliminated quickly in vivo and the brain exposure was not high, while the metabolite glucuronidin was eliminated slowly in vivo and the exposure was high. PK/PD study showed that the pharmacological action of glucuronidin was similar to that of the original drug in vivo and in vitro. This study provides an important basis for elucidating the substance basis of this drug in vivo.Read More
Study on the brain transport mechanism of anti-cerebral ischemia agentH004 has good permeability, but because it is the substrate of multiple efflux and uptake transporters, its low brain exposure may be the combined result of multiple transporters. The metabolite glucuronidin, though less permeable, is not a common substrate for efflux transporters, and glucose transporters contribute to brain intake, resulting in high and persistent intracerebral exposure.Read More
PK/PD Study of Immunoregulatory Point InhibitorPK/PD models of melanoma B16F10 and colon cancer MC38 xenograft tumors were established to explore the relationship between drug concentration in vivo and PD-L1 receptor occupation on the surface of tumor cells and the distribution of T lymphocyte subsets in plasma and tumor tissue infiltration after continuous administration of IMMH-010 in mice.Read More
Study on biotransformation of new lipid-regulating drugIMM-H007 can produce multiple metabolites catalyzed by various drug enzymes in different tissues in vivo. Under the action of intestinal flora and a variety of esterases in vivo, deacetyl group generates products M444, M402 and active metabolite M1. After M1 enters whole red blood cells, the main active metabolite MP is generated under the action of adenosine kinase. M1 and MP can be transformed into each other in whole blood and tissues in vivo, and each metabolite can produce a variety of binding products.Read More
Research and construction of key technologies for interaction between natural drugs and gut microbiotaIn order to elucidate the molecular mechanism of refractory natural drugs, we used berberine as a probe to study and construct the key technical system of the interaction between gut microbiota and natural drugs, and applied it to the mechanism research of many natural drugs. (Theranostics, 2017; Metabolism, 2017). These results have important implications in the field of gut microbiota drug metabolism and pharmacology.Read More
Metabolism and molecular mechanism of natural drugs based on gut microbiotaWe studied the metabolism and molecular mechanism of several natural drugs (berberine, albiflorin, paeoniflorin, etc.) in vivo by using the key technology of interaction between gut microbiota and natural drugs (Signal Transduct Target Ther, 2021; Theranostics, 2018 back cover paper), has important scientific value for revealing the mechanism of drug influence on gut-brain axis.Read More
Key technology development of a novel polypeptide TCP-1 applied in early diagnosis of colorectal cancerTCP-1 is a nine-peptide probe. Using 18F labeled TCP-1 and using PET-CT imaging technology, we established a new method and key core technology for early diagnosis of colorectal cancer with China's independent intellectual property rights. At the same time, the identification of TCP-1-targeted colorectal cancer binding sites can lead to the discovery of new tumor markers and important signaling pathways, and can be used for drug development.Read More
Mechanism research of the relationship between gut microbiota and clinical chronic disease and personalized treatmentWe used the multi-omics method combining gut bacteria genome and metabolome to explore the pathogenesis of intestinal bacteria and clinical chronic diseases, such as the molecular mechanism of uric acid nephropathy caused by abnormal gut microbiota metabolism (Acta Pharaceutica Sinica B, 2020). And the involvement of intestinal barrier dysfunction induced by intestinal bacterial disorders in the pathogenesis of pollen allergy (Engineering, 2020). Based on this, personalized drug therapy is expected to be realized.Read More
Drug-drug interactions mediated by ectopic activation of CYP3A4The drug-drug interaction mediated by heterotopic activation of CYP3A4 has attracted increasing attention. Citrinin, citrinin, flavonoids and 6-hydroxyflavones increase cell survival and in vivo exposure to metabolites by activating the metabolism of determinonidone. The B-aromatic ring, 7-position hydrophobic group and 4-position hydrogen bond receptor of flavonoids are the key pharmacophore of activation.Read More
Metabolic study of a novel anticancer drugAfter intravenous administration, the new anti-tumor drug MTC-220 mainly enters the intestinal tract through bile excretion, and then exits the body through feces, with a small amount of excretion in urine. In vitro cell experiments showed that MTC-220 was difficult to be absorbed through membrane due to its larger molecular weight. Liver perfusion experiments showed that OATPs could promote the uptake of MTC-220 in liver, and P-gp, BCRP and MRP2 could promote the bile excretion of MTC-220.Read More