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Lipid messenger prostaglandin E2 (PGE2) is a prostanoid that plays a key role in the generation of the inflammatory response. Currently available non-steroid anti-inflammatory drugs (NSAIDs) inhibit cyclooxygenase (COX)-1 and/or COX-2, all with significant cardiovascular, cerebrovascular, and gastrointestinal risks that have limited their utilization. Microsomal PGE2 synthase 1 (mPGES-1), an inducible enzyme responsible for overproduction of PGE2, may be a more promising target for a new type of anti-inflammatory drug without the adverse effects associated with the COX-1/2 inhibition. There have been extensive efforts to design and discover inhibitors targeting mPGES-1. Unfortunately, within the previously reported potent human mPGES-1 inhibitors, few have also been identified as potent inhibitors of mouse or rat mPGES-1, which prevents the use of well-established mouse or rat models of inflammation and pain in preclinical drug development. In a recently published study, we were able to design and discover a novel compound, denoted as UK4b, capable of potently inhibiting both human mPGES-1 (IC50=33 nM) and mouse mPGES-1 (IC50=157 nM). Additionally, our lab has designed and discovered another potent mPGES-1 inhibitor, KD001, and has computationally identified an FDA-approved drug, ceftriaxone, as a potent mPGES-1 inhibitor. In this dissertation, we demonstrate that UK4b, KD001, and ceftriaxone all have the desired potent anti-inflammatory and analgesic effects against post-operative pain in wild-type mice, adjuvant-induced knee joint arthritis in wild-type rats, and carrageenan-induced paw edema and hyperalgesia., © 2023 Madeline Stewart

This First Nations Community Engagement: Industry Guide Phase I (the Guide) was developed from discussions held with industry leaders involved with the Office of Indigenous Engagement, CQUniversity, and First Nations community members and leaders. This Guide draws on our own and our partners’ community engagement principles and practices. We plan to develop a Phase II Guide, which will include community engagement guidelines and protocols for industry from a First Nations perspective.

This First Nations Community Engagement: Industry Guide Phase I (the Guide) was developed from discussions held with industry2 leaders involved with the Office of Indigenous Engagement, CQUniversity, and First Nations3 community members and leaders. This Guide draws on our own and our partners’ community engagement principles and practices. We plan to develop a Phase II Guide, which will include community engagement guidelines and protocols for industry from a First Nations perspective.