Design, synthesis and biological activity evaluation of water-soluble borneol phosphate prodrug / 中国药科大学学报

@#Abstract: In this study, structural optimization of borneol was carried out to improve their solubility and promote their further application in stroke therapy. BP-3, a prodrug of borneol, was designed and synthesized based on the principle of phosphate modification. The solubility of BP-3 was determined by evaporative light scattering detector (ELSD), and the degree and speed of drug release were tested in mouse plasma, and the neuroprotective effect of BP-3 was evaluated in mouse model of transient middle cerebral artery occlusion (tMCAO). According to the results, BP-3 was completely soluble in saline at 20 mg/mL; in mouse plasma, approximately 40% of the borneol were released within 2 h; in the tMCAO mouse model, TTC staining showed that BP-3 was effective in reducing the infarct area; Nissl staining showed that BP-3 ameliorated the neuronal injury; the grip and grasping strength tests elucidated that BP-3 reduced the damage of sports ability caused by injury; and the rotating rod test proved that BP-3 could promote the recovery of motor ability in mice. BP-3 has good water solubility, suitable drug release rate and excellent neuroprotective effects, and has broad prospects for drug development.

Research progress of radioprobes targeting fibroblast activating protein / 中国药科大学学报

@#Fibroblast activating protein (FAP) is an important biomarker of cancer associated fibroblasts and activated fibroblasts, which is highly expressed in activated fibroblasts of many tumor and fibrotic tissues, but not in normal tissues and non malignant lesions. Therefore, FAP has become an excellent target for diagnosis and treatment of tumors and other diseases. PET imaging and internal radiotherapy based on FAP inhibitor (FAPI) have been used in the diagnosis and treatment of many diseases, such as cancer and fibrosis. We first introduce the mechanism of disease occurrence and progression mediated by FAP and its clinical significance as a therapeutic target.Then,we systematically summarize the FAP probes labeled with 125I, 68Ga, 64Cu and other radionuclides, including their structural evolution, imaging, biodistribution and pharmacokinetic properties.After that, the reported strategies to improve the pharmacokinetic properties and target affinity of probes are summarized, including the use of squaramide linkers,modification with albumin binding agent,the development of dual-targeting probes.Finally, some suggestions for the future development of novel radioactive probes targeting FAP and the clinical application of classical probes are proposed.