Archives

  • 2026-04
  • 2026-03
  • 2026-02
  • 2026-01
  • 2025-12
  • 2025-11
  • 2025-10
  • 2025-03
  • 2025-02
  • 2025-01
  • 2024-12
  • 2024-11
  • 2024-10
  • 2024-09
  • 2024-08
  • 2024-07
  • 2024-06
  • 2024-05
  • 2024-04
  • 2024-03
  • 2024-02
  • 2024-01
  • 2023-12
  • 2023-11
  • 2023-10
  • 2023-09
  • 2023-08
  • 2023-06
  • 2023-05
  • 2023-04
  • 2023-03
  • 2023-02
  • 2023-01
  • 2022-12
  • 2022-11
  • 2022-10
  • 2022-09
  • 2022-08
  • 2022-07
  • 2022-06
  • 2022-05
  • 2022-04
  • 2022-03
  • 2022-02
  • 2022-01
  • 2021-12
  • 2021-11
  • 2021-10
  • 2021-09
  • 2021-08
  • 2021-07
  • 2021-06
  • 2021-05
  • 2021-04
  • 2021-03
  • 2021-02
  • 2021-01
  • 2020-12
  • 2020-11
  • 2020-10
  • 2020-09
  • 2020-08
  • 2020-07
  • 2020-06
  • 2020-05
  • 2020-04
  • 2020-03
  • 2020-02
  • 2020-01
  • 2019-12
  • 2019-11
  • 2019-10
  • 2019-09
  • 2019-08
  • 2019-07
  • 2019-06
  • 2019-05
  • 2019-04
  • 2018-11
  • 2018-10
  • 2018-07

    • PF-562271 HCl: Selective ATP-Competitive FAK/Pyk2 Inhibit...

    2026-04-03

    PF-562271 HCl: Selective ATP-Competitive FAK/Pyk2 Inhibitor for Cancer Research

    Executive Summary: PF-562271 HCl is a potent, reversible, ATP-competitive inhibitor targeting focal adhesion kinase (FAK) and proline-rich tyrosine kinase 2 (Pyk2), with IC50 values of 1.5 nM and 14 nM, respectively, demonstrating approximately 10-fold selectivity for FAK over Pyk2 and over 100-fold selectivity against most other kinases except cyclin-dependent kinases (CDKs) (APExBIO product data). The compound dose-dependently inhibits tumor growth and metastasis in xenograft and transgenic mouse models, with an EC50 for FAK phosphorylation inhibition of 93 ng/mL (Adams et al., 2025). PF-562271 HCl is insoluble in water and ethanol but soluble at ≥26.35 mg/mL in DMSO with gentle warming, facilitating workflow integration for high-throughput cancer research (APExBIO product data). The inhibitor is a key pharmacological tool for dissecting the FAK/Pyk2 signaling axis in solid tumor and microenvironment studies (related article). For optimal stability and reproducibility, storage at -20°C is recommended.

    Biological Rationale

    Focal adhesion kinase (FAK) and proline-rich tyrosine kinase 2 (Pyk2) are non-receptor tyrosine kinases integral to cell adhesion, migration, proliferation, and survival (Adams et al., 2025). Dysregulation of FAK/Pyk2 signaling is implicated in tumorigenesis, cancer progression, and metastasis. Tumor cells exploit the FAK/Pyk2 axis to orchestrate changes in the tumor microenvironment, enhancing primary tumor growth and enabling metastatic spread by modulating both cancer and stromal cell behavior. Recent studies highlight the role of FAK/Pyk2 in the recruitment and transformation of myeloid progenitor cells (MPCs), which initiate pre-metastatic niches (PMNs) and facilitate circulating tumor cell (CTC) colonization (Adams et al., 2025). Thus, selective pharmacological inhibition of these kinases is a strategic approach in cancer research for dissecting mechanisms of tumor proliferation, invasion, and microenvironment modulation (see also—this article provides mechanistic depth, while the current piece emphasizes quantitative benchmarks and workflow parameters).

    Mechanism of Action of PF-562271 HCl

    PF-562271 HCl, developed by APExBIO, is an ATP-competitive, reversible inhibitor that binds to the catalytic domain of FAK and Pyk2, preventing phosphorylation events essential for downstream signaling. The compound exhibits an IC50 of 1.5 nM for FAK and 14 nM for Pyk2 in biochemical assays (APExBIO product data). Selectivity profiling shows over 100-fold reduced potency versus other protein kinases, except for some CDKs where cross-reactivity remains moderate. By blocking FAK/Pyk2 autophosphorylation, PF-562271 HCl suppresses focal adhesion turnover, cell motility, and integrin-mediated signaling. This results in decreased cancer cell migration, invasion, and proliferation. The compound also disrupts the interplay between tumor cells and stromal components, modulating the tumor microenvironment and impeding metastatic niche formation (Adams et al., 2025).

    Evidence & Benchmarks

    • PF-562271 HCl inhibits FAK kinase activity with an IC50 of 1.5 nM under standard ATP concentrations in vitro (APExBIO product data).
    • The compound shows an IC50 of 14 nM for Pyk2, reflecting ~10-fold selectivity for FAK over Pyk2 (APExBIO product data).
    • In cell-based assays, PF-562271 HCl suppresses FAK phosphorylation with an EC50 of 93 ng/mL (62.5–125 ng/mL range), leading to reduced tumor cell migration and proliferation (Adams et al., 2025).
    • In vivo, PF-562271 HCl dose-dependently inhibits primary tumor growth and metastasis in xenograft and transgenic mouse models, as measured by tumor volume reduction and metastatic lesion count (Adams et al., 2025).
    • The inhibitor demonstrates >100-fold selectivity against non-FAK/Pyk2 kinases, except for certain CDKs where off-target effects are moderate (APExBIO product data).
    • PF-562271 HCl is not effective in models where tumor progression is independent of FAK/Pyk2 signaling (related article—the current article offers a more nuanced discussion of selectivity and off-target limitations).

    Applications, Limits & Misconceptions

    PF-562271 HCl is widely used to study:

    • Tumor growth inhibition in solid tumor models (e.g., breast, pancreatic, prostate cancer).
    • Mechanisms of cancer cell adhesion, migration, invasion, and proliferation via modulation of the FAK/Pyk2 pathway.
    • Role of FAK/Pyk2 in tumor microenvironment modulation and PMN initiation.
    • Translational research exploring combinatorial regimens with chemotherapy, immunotherapy, or anti-angiogenic agents (see also—that article details protocol troubleshooting; this one emphasizes selectivity and application boundaries).

    Common Pitfalls or Misconceptions

    • PF-562271 HCl is not effective in tumors that do not rely on FAK/Pyk2 signaling for growth or survival.
    • The compound does not target receptor tyrosine kinases or pathways unrelated to the focal adhesion complex.
    • Off-target activity against some cyclin-dependent kinases (CDKs) may confound results; appropriate controls are necessary.
    • PF-562271 HCl is insoluble in water and ethanol; using inappropriate solvents may lead to inaccurate dosing or precipitation.
    • Long-term storage above -20°C can lead to compound degradation and reduced potency.

    Workflow Integration & Parameters

    PF-562271 HCl (SKU A8345) is supplied as a solid and should be dissolved in DMSO at concentrations ≥26.35 mg/mL with gentle warming. The compound is insoluble in water and ethanol, and solutions should be prepared fresh or stored in aliquots at -20°C to preserve activity. For cell-based assays, serial dilutions in DMSO are recommended, with final DMSO concentrations kept below 0.1% to avoid cytotoxicity. In vivo studies typically employ systemic administration at doses validated in the literature (e.g., 10–50 mg/kg, depending on model and endpoint) (see also—this piece provides real-world troubleshooting and data-driven dosing guidance, while the current article delivers comprehensive selectivity and benchmark data). The inhibitor's robust solubility in DMSO supports high-throughput screening and reproducible workflows.

    Conclusion & Outlook

    PF-562271 HCl is a rigorously validated, highly selective ATP-competitive FAK/Pyk2 inhibitor, indispensable for dissecting tumor cell-intrinsic and microenvironmental signaling in cancer research. Its nanomolar potency, robust selectivity, and workflow-friendly solubility make it a gold standard in translational oncology studies. As the understanding of FAK/Pyk2 biology deepens, PF-562271 HCl will continue to support innovative research on tumor growth, metastasis, and therapeutic resistance. For further details or to acquire the reagent, refer to the PF-562271 HCl product page from APExBIO.