ABSTRACT
@#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.
ABSTRACT
Chronic constipation is a common gastrointestinal disease severely affecting the patient׳s quality of life. The traditional treatment of constipation is the use of laxatives. Recently, several new drugs including lubiprostone, linaclotide and prucalopride have been approved for treatment of chronic constipation. However, a significant unmet medical need still remains, particularly among those patients achieving poor results by current therapies. The 5-HT4 receptor modulators velusetrag and naronapride, the guanylate cyclase C agonist plecanatide and the ileal bile acid transporter inhibitor elobixibat are recognized as the most promising drugs under investigation. Herein, we give a comprehensive review on the pharmacological therapeutics for the treatment of chronic constipation, with the purpose of reflecting the drug development trends in this field.