Do you want to get fit without dieting or exercising by tricking your body? This sounds like scifi, 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 SLUPP332, 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 preclinical data of different compounds, and 3) as always, review chemistry concepts.

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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 knockout mice
09:18 Drug design logic behind SLUPP332
11:02 Organic synthesis of SLUPP332 (too easy)
11:32 Molecular, structural, physiological and metabolic effects of SLUPP332
15:05 Outlook and conclusion

Key references:
PGC1α, 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 PGC1alpha | Cell 2006, 127, 1109
Distribution and Effects of Estrogen Receptors in Prostate Cancer: Associated Molecular Mechanisms | Frontiers in Endocrinology 2022, 12, 811578
Identification and structureactivity relationship of phenolic acyl hydrazones as selective agonists for the estrogenrelated orphan nuclear receptors ERRbeta and ERRgamma | J Med Chem 2005, 48, 3107
Exercise and PGC1 alphaIndependent Synchronization of Type I Muscle Metabolism and Vasculature by ERR gamma | Cell Metabolism 2011, 13, 283
Estrogenrelated receptorα coordinates transcriptional programs essential for exercise tolerance and muscle fitness | Mol Endocrinol 2014, 28, 2060
Synthetic ERRα/β/γ Agonist Induces an ERRαDependent 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 SLUPP compound with more chemistry information behind it:
Development and pharmacological evaluation of a new chemical series of potent panERR agonists, identification of SLUPP915 | 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 13 (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)