1.Bioactive peptides from scorpion venoms: therapeutic scaffolds and pharmacological tools.
Kamau PETER MUIRURI ; Jian ZHONG ; Bing YAO ; Ren LAI ; Lei LUO
Chinese Journal of Natural Medicines (English Ed.) 2023;21(1):19-35
Evolution and natural selection have endowed animal venoms, including scorpion venoms, with a wide range of pharmacological properties. Consequently, scorpions, their venoms, and/or their body parts have been used since time immemorial in traditional medicines, especially in Africa and Asia. With respect to their pharmacological potential, bioactive peptides from scorpion venoms have become an important source of scientific research. With the rapid increase in the characterization of various components from scorpion venoms, a large number of peptides are identified with an aim of combating a myriad of emerging global health problems. Moreover, some scorpion venom-derived peptides have been established as potential scaffolds helpful for drug development. In this review, we summarize the promising scorpion venoms-derived peptides as drug candidates. Accordingly, we highlight the data and knowledge needed for continuous characterization and development of additional natural peptides from scorpion venoms, as potential drugs that can treat related diseases.
Animals
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Scorpion Venoms/pharmacology*
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Peptides/pharmacology*
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Scorpions
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Drug Development
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Medicine, Traditional
2.Anticarin-β shows a promising anti-osteosarcoma effect by specifically inhibiting CCT4 to impair proteostasis.
Gan WANG ; Min ZHANG ; Ping MENG ; Chengbo LONG ; Xiaodong LUO ; Xingwei YANG ; Yunfei WANG ; Zhiye ZHANG ; James MWANGI ; Peter Muiruri KAMAU ; Zhi DAI ; Zunfu KE ; Yi ZHANG ; Wenlin CHEN ; Xudong ZHAO ; Fei GE ; Qiumin LV ; Mingqiang RONG ; Dongsheng LI ; Yang JIN ; Xia SHENG ; Ren LAI
Acta Pharmaceutica Sinica B 2022;12(5):2268-2279
Unlike healthy, non-transformed cells, the proteostasis network of cancer cells is taxed to produce proteins involved in tumor development. Cancer cells have a higher dependency on molecular chaperones to maintain proteostasis. The chaperonin T-complex protein ring complex (TRiC) contains eight paralogous subunits (CCT1-8), and assists the folding of as many as 10% of cytosolic proteome. TRiC is essential for the progression of some cancers, but the roles of TRiC subunits in osteosarcoma remain to be explored. Here, we show that CCT4/TRiC is significantly correlated in human osteosarcoma, and plays a critical role in osteosarcoma cell survival. We identify a compound anticarin-β that can specifically bind to and inhibit CCT4. Anticarin-β shows higher selectivity in cancer cells than in normal cells. Mechanistically, anticarin-β potently impedes CCT4-mediated STAT3 maturation. Anticarin-β displays remarkable antitumor efficacy in orthotopic and patient-derived xenograft models of osteosarcoma. Collectively, our data uncover a key role of CCT4 in osteosarcoma, and propose a promising treatment strategy for osteosarcoma by disrupting CCT4 and proteostasis.