Diabetes

The mainstream biotech drugs for treatment of type 2 diabetes are already gradually transition to the fourth generation of exogenous GLP-1 peptide analogues and DPP 4 inhibitors which was developed around the physiological function of pancreatic glucagon like peptide 1 (GLP-1), maintain the level of endogenous glp-1, from the first generation of animal insulin, the second generation of gene recombinant human insulin, the third generation of insulin analogs. Two varieties entered the first five in global sales of diabetes drugs since the first GLP-1 analogues drugs into the market in 2005. Compared with the insulin and its analogs, GLP-1 analogues drugs has the following significant advantages:
(1)GLP-1 analogues drugs increase the biological synthesis and secretion of insulin on the way of glucose dependent way onβ-cells, without the risk of hypoglycaemia, good security;
(2) GLP-1 analogues drugs can stimulate the proliferation and differentiation ofβ-cells , inhibite the poptosisof β-cell, increase insulin sensitivity, and help to delay the disease;
(3) GLP-1 analogues drugs can inhibite appetite and feeding, delay the stomach emptying and assist patients to lose weight.

Oncology

Prostate specific membrane antigen (PSMA) is an important drug targets of advanced prostate cancer, which are expressed in prostate cancer organizations, more than 10 times of normal prostate tissue, 100 times of brain tissue , 500-1000 times of liver and kidney, and the strength of expression become greater with the increases of malignant degree and metastatic tendency of prostate cancer.

Combined with target PSMA will not interfere the growth of tumor, so the monoclonal antibody targeted PSMA need connect to toxins, and the toxin enter the cellar internal through PSMA osmosis to targeted killer cells. But the choice of toxins, faces two worldwide technical problems:
(1) coupling of antibodies and toxin chemical connections need to be very stable, S involved in the process is complicated, expensive.
(2) The internalize efficiency of the toxinis is difficult to control, which is hard to achieve stability tumor inhibition effect, in complex physiological conditions.

HIV/AIDS

The AIDS virus (HIV), a kind of virus,which threat to human health seriously, lead to the AIDS, has become the fourth killer of human. "Fight disease" as one of the important goals in 2010 development report of the United Nations, in which the "fighting HIV/AIDS" is the first goal.The report pointed out that the spread of HIV/AIDS should be stop and reverse until 2015. Due to the lack of effective HIV vaccine, anti-HIV drugs safty and effectivly are an urgent medical researchers task in our country for AIDS prevention and treatment.

Invasion of the HIV-1 to the target cells is the first and important step for virus to the survival and pathogenesis in the host. The entry process involves multiple complex cellular biochemical reactions: the flow of the plasma membrane, the interactions of membrane receptor, the conformational changes of protein and even the interaction of protein and membrane lipid. The virus membrane protein gp120 and gp41 played an important role in this process. Specific process can be divided into the following steps: first, gp120 / gp41 compounds of HIV envelope protein, interact with CD4 receptor on the surface of the target cells through gp120; After that, the gp120 changed in conformation exposed the auxiliary receptor binding sites and combined with the chemokines CCR5 or CXCR4 of target cell membranes, this combination more induce the changes of membrane protein conformation; Finally, gp41 melt-film peptide (FP) pop-up and inserte into the target cell membranes, and then its N-terminal ribbon NHR formed tri-coiled coil structure, the structure is exposed, the CRH to extracellular side C function to its flip and finally formed the fusion activity six spiral - 3 NHR / 3 CRH, which will be the purpose that cell membranes and virus envelope is close enough to cause the membrane fusion. This integration process has become important targets for R&D of anti-HIV drugs, any effective suppression in the process steps of the integration, can achieve the purpose of preventing HIV invasion target cells in theory, so as to control the replication and infection of the virus to treatment of AIDS/HIV. Inhibitors act on the integration process, known collectively as HIV fusion inhibitors (Entry inhibitors), fusion inhibitors, act as the first step in the target cell of virus invasion relative to other role in a stage of the viral replication inhibitors, minimize the harm of human body, gradually become one of the hot spot of anti-HIV drugs’s R&D.

Analgesic

Pain therapy is the focus topic of the medical and pharmaceutical research. Although a large amount of work are done on pain management in the world and had made certain progress by human effort and material resources, but there are still a large number of patients facing the pain, especially chronic pain, unable to find a effective and specific therapies. Now Chemical medicine, such as salicylic acid kind of analgesics represented by aspirin, local anesthetics, antispasmodic and tricyclic chemical small molecules is the main drugs for pain therapy, but the tolerance, dependence, and other adverse reactions, influence the patient's quality of life badly, so the exploitation of biological macromolecules analgesic drugs with high efficiency and strong specificity become the urgent matter. Which is the key point of the national pharmaceutical industry, and has great space in research and development, production, sales and profit, as well as, the innovation drugs development of biological macromolecules is suit the strategic needs and direction of industrial structure in china.