Peptides›Metabolic›SR-9009

SR-9009

/ REV-ERB nuclear receptor agonist (small molecule)

TIER 3 · PreclinicalN = 0 · TESTING PENDINGMW 437.00 g·mol⁻¹

ALIAS · Stenabolic · SR9009 · SR-9009

—

Pass rate

Samples

Suppliers

Research use onlyAny dose figures below describe what specific cited studies used, reported factually. Nothing on this page is guidance for human use.READ FIRST →

Terms in this page you can click for a plain-English popup: , , , , , , , .

§ A · Identity

Primary sequence— sequence not captured —

MW · 437.00CLASS · REV-ERB nuclear receptor agonist (small molecule)CATEGORY · Metabolic

Tier 3. REV-ERB nuclear receptor agonist small molecule developed in the Burris laboratory (Scripps). Rodent metabolic, circadian, and oncology data. No human Phase 1 trial. Included on the WADA prohibited list as an unapproved metabolic modulator.

§ B · Mechanism of action

SR9009 is an agonist of the REV-ERB-alpha and REV-ERB-beta nuclear receptors, orphan receptors that function as transcriptional repressors and are core components of the molecular circadian clock. REV-ERB activation suppresses BMAL1 transcription, modifies hepatic and skeletal-muscle metabolic gene programs, and in rodent models has been reported to increase running endurance, reduce adiposity, and exert anti-tumour activity in selected cancer-cell models through metabolic-stress mechanisms. The very poor oral bioavailability of SR9009 in subsequent rodent studies has been raised as a confounder for the exercise-mimetic claims.

§ C · Human clinical evidence

Tier 3. Solt 2012 (Nature) reported in-vivo metabolic and endurance effects in mice administered SR9009 by intraperitoneal injection. Sulli 2018 (Nature) reported anti-cancer activity of REV-ERB agonists in cancer-cell models and rodent xenografts. Subsequent independent work raised concerns about SR9009 oral bioavailability and on-target versus off-target contributions to the in-vivo effects originally reported. No human study.

§ D · Primary literature

PubMed22460951Solt LA et al. — Regulation of circadian behaviour and metabolism by synthetic REV-ERB agonists · Nature · rodentSynthetic REV-ERB agonists SR9009 and SR9011 administered to mice altered circadian behaviour and produced metabolic effects including increased energy expenditure, reduced adiposity in diet-induced-obese mice, and altered hepatic and muscle metabolic gene expression.Limitations: Rodent only; intraperitoneal dosing; subsequent work questioned oral bioavailability and on-target attribution of some in-vivo effects.2012

PubMed29320480Sulli G et al. — Pharmacological activation of REV-ERBs is lethal in cancer and oncogene-induced senescence · Nature · in-vitroREV-ERB agonists including SR9009 produced selective cytotoxicity in cancer cells and oncogene-induced-senescent cells through metabolic-stress mechanisms; rodent xenograft models supported in-vivo activity.Limitations: In-vitro and rodent xenograft; mechanistic specificity of SR9009 effects subsequently questioned in independent work.2018

§ F · Safety signal

No human safety database. REV-ERB activation modifies circadian-clock outputs throughout the body; the long-term consequences of chronic pharmacological clock-modulation in humans are unstudied. WADA prohibited-list inclusion is a relevant disclosure for any reader engaged in tested-sport competition.

§ H · Regulatory status

Regulatory status

FDA status:: Not FDA-approved

§ I · Notable gaps and controversies

Vendor marketing of SR9009 (often as 'Stenabolic') as a recognised exercise mimetic and fat-loss aid relies on the original Solt 2012 rodent findings without disclosing the subsequent bioavailability and replication concerns. The WADA-prohibited status is rarely disclosed in vendor materials. No human Phase 1 trial has been published; vendor product purity and identity vary.