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👀 Do you want to get fit without dieting or exercising by tricking your body? This sounds like sci-fi, or like a scammy ad for a fat burning supplement. However, given recent advances in exercise mimetics and strong momentum behind treating obesity pharmacologically (most notably, semaglutide - Ozempic/Wegovy and tirzepatide - Mounjaro/Zepbound), this idea could reality sooner than some expect. 🧠 In this video we will discover SLU-PP-332, a small molecule that mimics endurance training and dieting in mice - without exercise or eating less. We will cover 1) the biochemical basics of exercise mimetics and mechanisms of action, 2) take a look at pre-clinical data of different compounds, and 3) as always, review chemistry concepts. https://www.patreon.com/totalsynthesis 🚀 Thanks to all channel supporters!!! https://www.instagram.com/totalsynthesis_official/ 👉 Follow me on Instagram for updates on random research, mechanism quizzes and interesting news! https://total-synthesis.com https://total-synthesis.com/exercise-mimetics-trick-your-body-into-burning-fat/ Disclaimer - This channel does not provide medical advice! No information on this channel is intended to be a substitute for professional medical advice, diagnosis or treatment. Always seek the advice of your physician or other qualified health care provider with any questions you may have regarding a medical condition or treatment and before undertaking a new health care regimen, and never disregard professional medical advice or delay in seeking it because of information on Youtube. 00:00 Trick your body into losing weight - is it possible? 01:22 Obesity problem, logic behind using drugs and limitations 02:31 GLP1 agonists 03:01 Exercise mimetic basics 04:04 Resveratrol's exercise mimicry, health benefits and unexpected effects 06:03 ERR up/downregulation can trigger major effects - transgenic and knock-out mice 09:18 Drug design logic behind SLU-PP-332 11:02 Organic synthesis of SLU-PP-332 (too easy) 11:32 Molecular, structural, physiological and metabolic effects of SLU-PP-332 15:05 Outlook and conclusion Key references: - PGC-1α, Inflammation, and Oxidative Stress: An Integrative View in Metabolism | Oxidative Medicine and Cellular Longevity, 2020, 1452696 - Caloric restriction and exercise “mimetics’’: Ready for prime time? | Pharmacological Research 2016, 103, 158 - Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha | Cell 2006, 127, 1109 - Distribution and Effects of Estrogen Receptors in Prostate Cancer: Associated Molecular Mechanisms | Frontiers in Endocrinology 2022, 12, 811578 - Identification and structure-activity relationship of phenolic acyl hydrazones as selective agonists for the estrogen-related orphan nuclear receptors ERRbeta and ERRgamma | J Med Chem 2005, 48, 3107 - Exercise and PGC-1 alpha-Independent Synchronization of Type I Muscle Metabolism and Vasculature by ERR gamma | Cell Metabolism 2011, 13, 283 - Estrogen-related receptor-α coordinates transcriptional programs essential for exercise tolerance and muscle fitness | Mol Endocrinol 2014, 28, 2060 - Synthetic ERRα/β/γ Agonist Induces an ERRα-Dependent Acute Aerobic Exercise Response and Enhances Exercise Capacity | ACS Chem. Biol. 2023, 18, 756 - A Synthetic ERR Agonist Alleviates Metabolic Syndrome | J. Pharmacol. Exp. Ther. 2023, 001733 Another related SLU-PP compound with more chemistry information behind it: Development and pharmacological evaluation of a new chemical series of potent pan-ERR agonists, identification of SLU-PP-915 | Eur J Med Chem 2023, 258, 115582 Some recommended books on organic synthesis: - Clayden, Greeves, Warren; Organic Chemistry (basic organic chemistry knowledge) - Wyatt, Warren; Organic Synthesis: The Disconnection Approach (excellent introduction to retrosynthesis) - Kurti, Czako; Strategic Applications of Named Reactions in Organic Synthesis (extensive toolkit of functional group reactions and applications thereof with common conditions) - Nicolaou; Classics in Total Synthesis 1-3 (the ultimate total synthesis trilogy) - Nicolaou; Molecules That Changed the World (the world's most important molecules and their impact on everyday life) - Carreira, Kvaerno; Classics in Stereoselective Synthesis (compilation of the groundbreaking methods of stereoselective synthesis and application to synthesis of stereochemically complex structures)

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GLP-1 Agonists are all the rage for weight loss, but using them improperly will lead to weight regain if you are not careful. I'm available for consultation if you need help properly using these medications or need help optimizing your health. You can book a one-hour consultation here: https://www.manmedicine.com/0f496e2a-c3bb-4ac0-bd4a-796232fdc305

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