944886-74-2Relevant articles and documents
Visualizing Tumors in Real Time: A Highly Sensitive PSMA Probe for NIR-II Imaging and Intraoperative Tumor Resection
Zhang, Longfei,Shi, Xiaojing,Li, Yuying,Duan, Xiaojiang,Zhang, Zeyu,Fu, Hualong,Yang, Xing,Tian, Jie,Hu, Zhenhua,Cui, Mengchao
, p. 7735 - 7745 (2021)
Owing to the complex anatomical structure, precise resection of a tumor while maintaining adjacent tissue is a challenge in radical prostatectomy for prostate cancer (PCa). Optical imaging in near-infrared window II (NIR-II) is a promising technology for intraoperative guidance, whereas there is no available probe for PCa yet. In this article, a novel probe (PSMA-1092) bearing two prostate-specific membrane antigen (PSMA) binding motifs was developed, displaying excellent optical properties (λmax = 1092 nm) and ultrahigh affinity (Ki = 80 pM) toward PSMA. The tumor was visualized with high resolution (tissue-to-normal tissue ratio = 7.62 ± 1.05) and clear margin by NIR-II imaging using PSMA-1092 in a mouse model. During the tumor resection, residual tumors missed by visible inspection were detected by the real-time imaging. Overall, PSMA-1092 displayed excellent performance in delineating the tumor margin and detecting residual tumors, demonstrating promising potential for precise PCa tumor resection in clinical practice.
Small-molecule inhibitors of cathepsin L incorporating functionalized ring-fused molecular frameworks
Song, Jiangli,Jones, Lindsay M.,Chavarria, Gustavo E.,Charlton-Sevcik, Amanda K.,Jantz, Adam,Johansen, Audra,Bayeh, Liela,Soeung, Victoria,Snyder, Lindsey K.,Lade Jr., Shawn D.,Chaplin, David J.,Trawick, Mary Lynn,Pinney, Kevin G.
supporting information, p. 2801 - 2807 (2013/06/27)
Cathepsin L is a cysteine protease that is upregulated in a variety of malignant tumors and plays a significant role in cancer cell invasion and migration. It is an attractive target for the development of small-molecule inhibitors, which may prove beneficial as treatment agents to limit or arrest cancer metastasis. We have previously identified a structurally diverse series of thiosemicarbazone-based inhibitors that incorporate the benzophenone and thiochromanone molecular scaffolds. Herein we report an important extension of this work designed to explore fused aryl-alkyl ring molecular systems that feature nitrogen atom incorporation (dihydroquinoline-based) and carbon atom exclusivity (tetrahydronaphthalene-based). In addition, analogues that contain oxygen (chromanone-based), sulfur (thiochroman-based), sulfoxide, and sulfone functionalization have been prepared in order to further investigate the structure-activity relationship aspects associated with these compounds and their ability to inhibit cathepsins L and B. From this small-library of 30 compounds, five were found to be strongly inhibitory (IC50 50 = 164 nM. All of the compounds evaluated were inactive (IC50 >10,000 nM) as inhibitors of cathepsin B, thus establishing a high degree (>20-fold) of selectivity (cathepsin L vs. cathepsin B) for the most active cathepsin L inhibitors in this series.
