Nonsteroidal SARM: Benzonitrile-oxadiazole scaffold with AR binding Ki 7 nM (comparable to DHT 10 nM), first described 2011, tissue-selective levator ani vs. prostate activity, oral bioavailability 27-75%
Clinical Development: Phase 1 ER+/HER2- breast cancer (MTD 100 mg/day, t½ 44.7 hours), active Phase 1/2 trial (NCT05573126, Ellipses Pharma EP0062), discontinued for sarcopenia indications
Safety Warnings: Dose-limiting hepatotoxicity (AST 59.1%, ALT 45.5%), cholestatic liver injury case reports, cardiotoxicity (myocarditis/myopericarditis), HPG axis suppression, WADA prohibited S1.2, not approved for medical use
Oral semaglutide is a 31-amino acid GLP-1 receptor agonist with engineered modifications (Aib8, C-18 fatty di-acid, Lys34Arg) enabling oral bioavailability via SNAC absorption enhancement technology. Research demonstrates glycemic control comparable to injectable GLP-1 agonists with 15.1% weight loss (50mg dose, OASIS-1 trial).
Pan-ERR Agonist Exercise Mimetic: Hydrazone small molecule (E)-4-hydroxy-N'-(naphthalen-2-ylmethylene)benzohydrazide, Saint Louis University design, activates ERRalpha/beta/gamma (EC50 98/230/430 nM), 10+ publications, all preclinical
Multi-System Metabolic Reprogramming: 70% increased endurance, 12% body weight loss, mitochondrial biogenesis via PGC-1alpha/AMPK/TFAM cascade, type IIa muscle fiber conversion, 25% increased fatty acid oxidation, reverses age-related kidney dysfunction
Clinical Status: No human trials (as of Feb 2026), all data from mouse models, well-tolerated in 8-week studies, successor compound SLU-PP-915 with improved oral bioavailability developed 2026
Triple monoamine reuptake inhibitor (TRI) potently inhibiting presynaptic reuptake of serotonin, norepinephrine, and dopamine with IC₅₀ values: NET 1.7-3.2 nM, SERT 11 nM, DAT 8.0-65 nM
Produces approximately twice the weight loss of currently marketed anti-obesity medications; Phase II trials: 9-11% body weight reduction over 24 weeks at therapeutic doses (0.5-1.0 mg)
FDA orphan drug designation for Tesomet (tesofensine + metoprolol) in Prader-Willi syndrome (March 2021) and hypothalamic obesity (July 2021); exceptionally long half-life (~9 days) enabling once-daily dosing
