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    • Canagliflozin (hemihydrate): SGLT2 Inhibitor for Glucose ...

    2025-10-26

    Canagliflozin (hemihydrate): SGLT2 Inhibitor for Glucose Metabolism Research

    Executive Summary: Canagliflozin (hemihydrate) is a chemically defined SGLT2 inhibitor used to study glucose homeostasis by blocking renal glucose reabsorption (ApexBio product C6434). Its high purity (≥98%) and solubility in organic solvents enable precise experimental applications (ApexBio). Recent peer-reviewed evidence confirms it does not inhibit mTOR pathways in yeast models, delineating its pathway specificity (Breen et al. 2025). The compound is strictly for research use and not suitable for therapeutic or diagnostic purposes (ApexBio). This review distinguishes Canagliflozin's validated mechanism and corrects misconceptions about its off-target effects.

    Biological Rationale

    Glucose homeostasis is critical in metabolic disorder research. Sodium-glucose co-transporter 2 (SGLT2) is a membrane protein predominantly expressed in the renal proximal tubule. SGLT2 mediates the reabsorption of filtered glucose from the glomerular filtrate back into circulation. Inhibition of SGLT2 reduces renal glucose reabsorption, resulting in increased urinary glucose excretion and decreased blood glucose levels. SGLT2 inhibitors are thus essential tools in diabetes mellitus research, allowing targeted modulation of glucose handling in preclinical models (ApexBio). Canagliflozin (hemihydrate) is a prototypical small molecule SGLT2 inhibitor for these applications. For a broader mechanistic comparison, see Canagliflozin Hemihydrate: Mechanistic Insights for Glucose Homeostasis; this article extends the discussion by providing validated pathway exclusions and peer-reviewed benchmarks.

    Mechanism of Action of Canagliflozin (hemihydrate)

    Canagliflozin (hemihydrate) selectively inhibits SGLT2 by binding to its active site, competitively blocking glucose transport. The chemical structure, (2S,3R,4R,5S,6R)-2-(3-((5-(4-fluorophenyl)thiophen-2-yl)methyl)-4-methylphenyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol, underlies its specificity. Its molecular formula is C24H26FO5.5S, with a molecular weight of 453.52 g/mol. The compound is insoluble in water but dissolves readily in ethanol (≥40.2 mg/mL) and DMSO (≥83.4 mg/mL), facilitating use in in vitro and animal studies. By inhibiting SGLT2, Canagliflozin (hemihydrate) decreases glucose reuptake in the kidney, increasing the fractional excretion of glucose and lowering systemic glucose levels. This mechanism does not involve direct action on insulin secretion or sensitivity, distinguishing it from other antidiabetic agents. For a systems biology perspective, Canagliflozin (Hemihydrate): Unveiling SGLT2 Inhibition Distinctions offers complementary context; this article clarifies specificity boundaries and peer-validated exclusions.

    Evidence & Benchmarks

    • Canagliflozin (hemihydrate) exhibits high purity (≥98%) as confirmed by HPLC and NMR, ensuring experimental reliability (ApexBio).
    • Demonstrated solubility in DMSO (≥83.4 mg/mL) and ethanol (≥40.2 mg/mL) enables flexible assay design (ApexBio).
    • In yeast-based mTOR pathway screening, Canagliflozin showed no evidence of TOR inhibition at relevant concentrations (Breen et al. 2025, DOI).
    • Canagliflozin's effect is specific to SGLT2 and does not extend to mTOR or TORC1 pathways under standard screening conditions (Breen et al. 2025, DOI).
    • Recommended storage is at -20°C with blue ice shipping to maintain compound stability and purity (ApexBio).
    • Not intended for diagnostic or therapeutic use; strictly for research applications (ApexBio).

    Applications, Limits & Misconceptions

    Canagliflozin (hemihydrate) is utilized in:

    • Glucose metabolism and diabetes mellitus research, enabling precise interrogation of renal glucose handling.
    • Metabolic disorder studies requiring reversible, non-insulinotropic modulation of glycemia.
    • Pathway dissection where SGLT2-specific inhibition is critical for distinguishing renal versus pancreatic contributions.

    Importantly, recent experimental data confirm that Canagliflozin (hemihydrate) does not inhibit mTOR signaling in yeast—contrary to some early hypotheses (Breen et al. 2025). For a detailed discussion of this update and how it clarifies earlier pathway ambiguities, see Expanding SGLT2 Inhibitor Utility: Recent mTOR Evidence. This article updates and refines the conclusions presented there by incorporating direct experimental exclusion of mTOR effects.

    Common Pitfalls or Misconceptions

    • Canagliflozin (hemihydrate) is not an mTOR inhibitor: No TOR pathway inhibition was detected in yeast at testable doses (Breen et al. 2025).
    • Not suitable for long-term solution storage: Solutions degrade; use fresh preparations for each experiment (ApexBio).
    • For research use only: Not for human or veterinary diagnostic or therapeutic applications (ApexBio).
    • Specificity is for SGLT2: Does not directly affect insulin secretion, insulin sensitivity, or unrelated metabolic enzymes.
    • Solubility limits in water: Compound is insoluble in aqueous buffers; use appropriate organic solvents for dissolution.

    Workflow Integration & Parameters

    To integrate Canagliflozin (hemihydrate) into experimental workflows:

    • Store the dry compound at -20°C; avoid repeated freeze-thaw cycles.
    • Dissolve in DMSO or ethanol immediately prior to use; typical working concentrations range from 0.1–100 μM for in vitro assays.
    • Prepare fresh solutions; do not store in solution for extended periods.
    • Confirm SGLT2 expression in the model system to ensure target engagement.
    • Monitor glucose concentrations in culture medium, perfusate, or urine as a direct readout.
    • Follow institutional and regulatory guidelines for small molecule handling and disposal.

    For strategic guidance on experimental design and pathway dissection using this compound, see Canagliflozin (Hemihydrate): Mechanistic Precision and Strategy, which this article expands by providing updated pathway exclusion and peer-reviewed workflow validation.

    Conclusion & Outlook

    Canagliflozin (hemihydrate) is a validated, high-purity SGLT2 inhibitor that supports advanced research in glucose metabolism and diabetes pathways. Its specificity is rigorously established; it does not inhibit mTOR pathways under standard research conditions. Proper handling and application protocols are essential for reproducible results. Future research may further define its use in multi-pathway metabolic models, but current data confirm its precise mechanism and application boundaries. For ordering and technical details, consult the Canagliflozin (hemihydrate) product page.