Article
Chemistry, Medicinal
Jinny Claire Lee, Hyeri Park, Lisa M. Eubanks, Beverly Ellis, Bin Zhou, Kim D. Janda
Summary: This study implements immunopharmacotherapy to combat benzimidazole-derived new psychoactive substance (NPS) opioids. By producing antibodies with high titers and nanomolar affinity, psychoactive and physiological responses to NPS opioids can be mitigated. Additionally, the pharmacokinetics of these drugs and the challenges faced by traditional pharmaceutical opioid antagonists are discussed.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Yuan-yuan Wei, Yan Ma, Song-yu Yao, Ling-hui Kong, Xiao Liu, Jing-rui Chai, Jing Chen, Wei Li, Yu-jun Wang, Li-ming Shao, Jing-gen Liu
Summary: SLL-039 and SLL-1206 are potent and long-lasting analgesic agents with antipruritic effects, showing potential as novel analgesics with fewer side effects. They activate K opioid receptors and do not cause sedation or conditioned place aversion, suggesting their promise as effective pain relief options.
ACTA PHARMACOLOGICA SINICA
(2022)
Article
Chemistry, Medicinal
Mengna Zhang, Biao Xu, Ning Li, Run Zhang, Qinqin Zhang, Xuerui Shi, Kangtai Xu, Jian Xiao, Dan Chen, Jiandong Niu, Yonghang Shi, Quan Fang
Summary: Stable and orally bioavailable analogues of DN-9 achieving peripherally restricted analgesia with reduced side effects have been developed. Among these analogues, analogue 1 showed improved potency for kappa-opioid and NPFF2 receptors and exhibited powerful, long-lasting antinociceptive effects in mouse models of acute, inflammatory, and neuropathic pain without significant side effects at effective analgesic doses.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Zhuang Miao, Yuhan Zhong, Yu Gan, Kequan Fu, Wencheng Liu, Zhihua Cao, Tiantian Zhao, Ziyuan Li, Ao Hai, Yanlai Peng, Zeping Zuo, Tian Zhang, Shilong Hu, Chunxia Chen, Ting Kang, Tianguang Huang, Dong Guo, Bowen Ke
Summary: A new class of dual mu OR agonist/sigma R-1 antagonist has been reported, which exhibits robust analgesic effects with reduced side effects. The optimal compound, 4x, shows potent mu OR agonism activity and good sigma R-1 inhibitory activity, making it a promising lead compound for developing safer opioids.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Substance Abuse
Marthe M. Vandeputte, Meng-Hua M. Tsai, Li Chen, Grant C. Glatfelter, Donna Walther, Christophe P. Stove, Lei Shi, Michael H. Baumann
Summary: The emergence of non-fentanyl novel synthetic opioids (NSOs) is contributing to the opioid overdose crisis. Neuropharmacological examination showed that these non-fentanyl NSOs have high selectivity for the mu-opioid receptor (MOR) and similar functional potencies to morphine and fentanyl. In vivo experiments in rats demonstrated that these non-fentanyl NSOs induce opioid-like effects, with nitazenes being the most potent.
DRUG AND ALCOHOL DEPENDENCE
(2023)
Article
Biochemistry & Molecular Biology
Joshua A. Lutz, Agnieszka Sulima, Eugene S. Gutman, Eric W. Bow, Dan Luo, Sophia Kaska, Thomas E. Prisinzano, Carol A. Paronis, Jack Bergman, Gregory H. Imler, Andrew T. Kerr, Arthur E. Jacobson, Kenner C. Rice
Summary: All possible diastereomeric C9-hydroxymethyl-, hydroxyethyl-, and hydroxypropyl-substituted 5-phenylmorphans were synthesized to explore the three-dimensional space around the C9 substituent in search for potent MOR partial agonists. Many of these compounds exhibited nanomolar or subnanomolar potency and were fully efficacious. One compound in particular, 21, showed good potency and efficacy as a MOR partial agonist, as well as selectively activating G-protein signaling pathway. Overall, the study highlights the importance of structural modification in developing new opioids with improved analgesic properties.
Article
Chemistry, Medicinal
Elisabet Viayna, Nicolas Coquelle, Monika Cieslikiewicz-Bouet, Pedro Cisternas, Carolina A. Oliva, Elena Sanchez-Lopez, Miren Ettcheto, Manuela Bartolini, Angela De Simone, Mattia Ricchini, Marisa Rendina, Megane Pons, Omidreza Firuzi, Belen Perez, Luciano Saso, Vincenza Andrisano, Florian Nachon, Xavier Brazzolotto, Maria Luisa Garcia, Antoni Camins, Israel Silman, Ludovic Jean, Nibaldo C. Inestrosa, Jacques-Philippe Colletier, Pierre-Yves Renard, Diego Munoz-Torrero
Summary: By combining the scaffolds of the cholinesterase inhibitor huprine Y and the antioxidant capsaicin, compounds with nanomolar potencies towards AChE and BChE were created, demonstrating potential therapeutic effects for Alzheimer's disease.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biotechnology & Applied Microbiology
Juan F. Martin, Paloma Liras
Summary: Recent studies have revealed that the penV gene of Penicillium chrysogenum encodes a TRP ion channel involved in the control of penicillin biosynthesis. This TRP protein may increase the expression of specific genes through calcium signaling cascade and participate in regulatory mechanisms of secondary metabolite biosynthesis in fungi.
CURRENT RESEARCH IN BIOTECHNOLOGY
(2021)