What Is Defactinib Hydrochloride and How Does It Work?

Defactinib hydrochloride (also known as VS-6063 or PF-04554878) is a selective, ATP-competitive inhibitor of focal adhesion kinase (FAK, also called PTK2) and the related kinase PYK2. FAK is a non-receptor tyrosine kinase that plays a central role in integrin-mediated signaling, regulating cell adhesion, proliferation, survival, and migration.

By binding to the ATP-binding pocket of FAK, defactinib blocks autophosphorylation at the key activation site (Y397) and downstream signaling through pathways including PI3K/AKT and MAPK/ERK. This inhibition can suppress tumor cell proliferation, reduce cancer stem cell populations, and modulate the immunosuppressive tumor microenvironment.

Defactinib has been investigated in clinical trials for mesothelioma, ovarian cancer, and pancreatic cancer, making it a valuable tool compound for translational oncology research.

Solubility, Reconstitution, and Formulation Guidelines

Defactinib hydrochloride, as a hydrochloride salt, generally exhibits improved aqueous solubility compared to the free base form. Key solubility guidance for researchers:

• DMSO: Defactinib hydrochloride is soluble in DMSO. Prepare a concentrated stock solution (e.g., 10–50 mM) in DMSO, aliquot, and store at –20 °C under desiccation to avoid freeze–thaw degradation.
• Aqueous buffers: The hydrochloride salt has improved solubility in aqueous media relative to the free base; consult your solubility data sheet for confirmed values.
• In vivo formulations: For animal studies, common vehicles include 0.5% methylcellulose or PEG400/saline combinations. Always verify vehicle compatibility with your experimental model.

Note: Specific solubility values (mg/mL or mM) are not confirmed in the current source material. Researchers should consult the Certificate of Analysis (CoA) or contact Aladdin Scientific technical support for verified solubility data.

Storage, Stability, and Handling Precautions

Proper storage and handling are essential to maintain the activity and integrity of Defactinib hydrochloride:

• Storage temperature: Store the bulk powder at –20 °C in a tightly sealed container, protected from light and moisture. Long-term storage at –80 °C may further improve stability.
• Stock solutions: Aliquot reconstituted solutions to minimize freeze–thaw cycles. DMSO stock solutions stored at –20 °C are typically stable for several months; verify with CoA or stability data.
• Handling: As with all potent kinase inhibitors, handle with appropriate personal protective equipment (PPE) including gloves, lab coat, and eye protection. Avoid inhalation of powder. Refer to the Safety Data Sheet (SDS) for full hazard information.
• Working solutions: Prepare fresh working dilutions in cell culture media or buffer on the day of use wherever possible to minimise compound degradation.

Specific shelf-life and stability data should be confirmed on the product CoA provided with each lot.

Ordering, Availability, and Product Specifications

Aladdin Scientific supplies Defactinib hydrochloride under SKU D656186. Key ordering information:

• Cross-reference: This product corresponds to MCE catalog number HY-12289A, facilitating straightforward literature cross-referencing.
• Purity: Purity specifications are provided on the product Certificate of Analysis (CoA). For high-sensitivity assays, confirm purity meets your experimental requirements before ordering.
• Available quantities: Contact Aladdin Scientific or visit the product page for current stock levels and available pack sizes.
• Custom synthesis / bulk orders: For bulk quantities or custom formulations, please contact our sales team directly.
• Documentation: CoA, SDS, and NMR/HPLC data are available upon request or via the product page on the Aladdin Scientific website.

For technical questions about applications or experimental design, contact Aladdin Scientific technical support.