SLU-PP-915 (ERR Pan-Agonist) Research Standard

SLU-PP-915 is a synthetic small-molecule pan-agonist of the Estrogen-Related Receptor (ERR) family, specifically targeting ERRα, ERRβ, and ERRγ. Developed as a second-generation analog of SLU-PP-332, this compound incorporates a phenylboronic acid pharmacophore that preserves potent ERR activation while significantly enhancing metabolic stability and oral bioavailability. As an “exercise mimetic,” SLU-PP-915 is utilized in laboratory research to study the PGC-1α-linked transcriptional programs that regulate mitochondrial biogenesis, fatty-acid oxidation, and autophagy-lysosomal function.

Technical Specifications

Mechanism of Action & Research Context

SLU-PP-915 modulates metabolic phenotype by directly activating nuclear receptors that function as master transcriptional regulators of oxidative metabolism.

• ERR Isoform Agonism: SLU-PP-915 binds the ligand-binding domain of all three ERR isoforms, with reported EC50 values of approximately 414 nM (ERRα), 435 nM (ERRβ), and 378 nM (ERRγ) in cell-based co-transfection assays.

• Transcriptional Regulation: The compound promotes the recruitment of coactivators to drive the expression of canonical ERR target genes such as PGC1α, PDK4, and LDHA. It is notably selective for the ERR subfamily, demonstrating no significant activity at classical estrogen receptors (ERα or ERβ).

• Autophagy-Lysosomal Axis: Beyond mitochondrial biogenesis, SLU-PP-915 upregulates Transcription Factor EB (TFEB) and downstream markers (e.g., LAMP1, LAMP2, CTSD), providing a mechanism to study the coordination between metabolic demand and autophagic clearance in cardiac and skeletal muscle models.

• Structural Optimization: The substitution of the phenolic hydrogen-bond donor (found in SLU-PP-332) with a phenylboronic acid group was a strategic development to improve microsomal stability, allowing for oral administration in murine models.

Research Applications

SLU-PP-915 serves as a high-precision chemical probe for isolating the effects of chronic ERR activation.

Primary fields of in vitro and in vivo laboratory investigation include:

• Exercise Mimetic Research: Evaluating transcriptional signatures and exercise capacity (e.g., time-to-exhaustion) in murine treadmill models.

• Mitochondrial Biogenesis & Oxidative Metabolism: Quantifying mitochondrial density and oxidative phosphorylation efficiency in response to pharmacologically induced ERR activation.

• Cardiac Function: Investigating the protective effects of ERR activation in pressure-overload heart failure models (e.g., transaortic constriction), particularly regarding lipid metabolism and TFEB-mediated autophagy.

• Metabolic Reprogramming: Mapping shifts in substrate utilization (e.g., increased fatty acid oxidation) driven by ERR-mediated gene networks.

Storage & Handling Guidelines

Store at controlled room temperature. Keep tightly closed. Liquid formats: do not refrigerate or freeze. Cold storage may cause the solution to cloud or precipitate. If this occurs, return to room temperature and mix until clear.

Storage guidance is a house recommendation. Analytical documentation is per-lot release testing.