AZ505 SETD7 Inhibitor: Key Facts & FAQs

AZ505 is a potent and selective small-molecule inhibitor of SETD7 (SET7/9), a lysine methyltransferase that monomethylates histone H3 at lysine 4 (H3K4me1) and a range of non-histone substrates, making it a valuable tool compound for epigenetics research.

Target

SETD7 (SET7/9, KMT7) lysine methyltransferase

Mechanism of Action

Competitive inhibitor with respect to the peptide substrate; binds the substrate-binding groove of SETD7

Selectivity

Selective for SETD7 over a broad panel of other methyltransferases; refer to primary literature for full profiling data

Solubility

Soluble in DMSO; prepare stock solutions in DMSO and dilute into aqueous buffer immediately before use

Storage

Store as supplied at -20 °C, protected from light and moisture; avoid repeated freeze-thaw cycles

Research Applications

Epigenetics, gene regulation, cancer biology, metabolic disease, and non-histone substrate methylation studies

What Is AZ505 and How Does It Work?

AZ505 is a synthetic small-molecule inhibitor specifically designed to target SETD7 (also known as SET7/9 or KMT7), a member of the SET-domain-containing lysine methyltransferase family. SETD7 catalyzes the monomethylation of histone H3 at lysine 4 (H3K4me1), a mark associated with active enhancers, and also methylates numerous non-histone proteins including p53, TAF10, and estrogen receptor alpha, thereby regulating their stability and transcriptional activity.

AZ505 acts as a substrate-competitive inhibitor: it occupies the peptide substrate-binding groove of SETD7 rather than competing with the cofactor S-adenosyl-L-methionine (SAM). This mode of action provides a mechanistic basis for selectivity, since the substrate-recognition channel differs substantially among SET-domain methyltransferases. By blocking SETD7 activity, AZ505 enables researchers to dissect the functional consequences of SETD7-mediated methylation events in cellular and biochemical contexts.

Selectivity Profile of AZ505

A key attribute of AZ505 as a chemical probe is its selectivity for SETD7 relative to other protein methyltransferases. Selectivity profiling against a panel of SET-domain and non-SET-domain methyltransferases is an essential quality criterion for any tool compound intended for epigenetics research. Users are strongly encouraged to consult the original peer-reviewed literature describing AZ505 for detailed IC₅₀ values and counter-screen data, as these numbers are compound-lot- and assay-format-dependent.

When designing experiments with AZ505, researchers should include appropriate controls, such as a structurally matched negative-control compound where available, to distinguish on-target SETD7 inhibition from off-target effects. Orthogonal validation using genetic approaches (e.g., SETD7 siRNA knockdown or CRISPR knockout) is recommended to corroborate pharmacological findings.

Handling, Solubility, and Storage Recommendations

AZ505 is supplied as a solid and is soluble in dimethyl sulfoxide (DMSO). To prepare a stock solution, dissolve AZ505 in DMSO to a concentration appropriate for your experimental needs, typically 10–100 mM, and vortex or sonicate gently to ensure complete dissolution. Stock solutions should be aliquoted to avoid repeated freeze-thaw cycles, which can compromise compound integrity over time.

When diluting into aqueous media or cell culture, ensure the final DMSO concentration does not exceed levels tolerated by your biological system (commonly ≤0.1% v/v for cell-based assays). Always include a vehicle-only (DMSO) control at the same final concentration. Store the compound at -20 °C in a tightly sealed container, protected from light and moisture. Verify actual solubility and stability under your specific assay conditions before initiating experiments.

Research Applications of AZ505

AZ505 has been employed as a pharmacological tool to investigate the biological roles of SETD7 across multiple research areas. In cancer biology, SETD7-mediated methylation of p53 at lysine 372 stabilizes p53 and promotes its transcriptional activity, while methylation of other substrates has been linked to NF-κB signaling and Hippo pathway regulation. AZ505 therefore provides a means to probe these pathways without permanent genetic alteration of the cell.

In metabolic and cardiovascular research, SETD7 has been implicated in the regulation of genes involved in glucose homeostasis and inflammatory responses in endothelial cells. Researchers studying these processes can use AZ505 to acutely inhibit SETD7 activity and measure downstream transcriptional or proteomic changes. Additionally, AZ505 serves as a starting scaffold for medicinal chemistry efforts aimed at developing next-generation SETD7 inhibitors with improved potency or pharmacokinetic properties.

Ordering, Purity, and Quality Information

AZ505 is available from Aladdin Scientific under SKU A607844. The compound is intended for research use only and is not approved for use in humans or animals as a therapeutic agent. Purity is assessed by HPLC and/or NMR; please refer to the Certificate of Analysis (CoA) supplied with each lot for specific purity data. Lot-specific CoA documents can be requested from Aladdin Scientific customer service.

For bulk quantities, custom formulations, or technical questions regarding AZ505, contact Aladdin Scientific's technical support team. When placing an order, please confirm the required quantity, desired format (neat solid or solution), and any special handling requirements. Aladdin Scientific's quality management processes ensure traceability and consistency across lots.

Frequently asked questions

What is the molecular target of AZ505 and what biological process does it regulate?

AZ505 selectively inhibits SETD7 (SET7/9, KMT7), a SET-domain lysine methyltransferase. SETD7 monomethylates histone H3K4 at enhancers and methylates non-histone proteins such as p53, ER-alpha, and TAF10, thereby regulating gene expression, protein stability, and signaling pathways relevant to cancer, metabolism, and inflammation.

How should I prepare and store AZ505 stock solutions for cell-based assays?

Dissolve AZ505 in DMSO to prepare a concentrated stock solution (e.g., 10–100 mM), aliquot to avoid repeated freeze-thaw cycles, and store at -20 °C protected from light and moisture. When adding to cell culture media, dilute so that the final DMSO concentration does not exceed approximately 0.1% v/v, and always include a matched DMSO vehicle control.

Is AZ505 selective for SETD7 over other methyltransferases?

AZ505 was developed as a selective SETD7 inhibitor and has been profiled against other methyltransferases to demonstrate preferential activity toward SETD7. However, users should consult the primary literature for quantitative selectivity data (IC₅₀ values across a panel), as these figures are assay-dependent. Orthogonal genetic controls, such as SETD7 knockdown, are recommended to confirm on-target activity in your specific model.

What controls should I include when using AZ505 in epigenetics experiments?

Always include a DMSO vehicle control at the same final solvent concentration. Where available, use a structurally related inactive analog as a negative control to rule out non-specific compound effects. Genetic controls, such as SETD7 siRNA knockdown or CRISPR knockout cells, provide orthogonal validation of phenotypes observed with AZ505.

Can AZ505 be used in in vivo studies?

AZ505 is primarily characterized as an in vitro biochemical and cell-based tool compound. Its suitability for in vivo use depends on its pharmacokinetic properties (absorption, distribution, metabolism, excretion) in the relevant animal model, which should be experimentally determined. Researchers planning in vivo studies should consult the primary literature and conduct preliminary pharmacokinetic assessments before proceeding.

References

1. Primary discovery publication describing AZ505 as a SETD7 inhibitor — specific authors, journal, volume, pages, and year not confirmed from supplied source material; please verify.
2. SETD7 (SET7/9) biochemistry and substrate methylation review — specific citation not confirmed from supplied source material; please verify.

Products are supplied for research and development use only. Not for use in humans, animals, diagnosis, or therapy.