benzesulfonate (PF-562271) / Pfizer - LARVOL DELTA

The Integrin-Mediated Focal Adhesion Is Critically Involved in the Macrophage-to-Myofibroblast Transition in Subretinal Fibrosis. (PubMed, Am J Pathol) - "Intraperitoneal administration PF562271 reduced adhesion molecules ITGB2 and ITGAL expression on circulating monocytes and alleviated subretinal fibrosis. These findings identify integrin-FAK-mediated mechanotransduction as a key regulator of macrophage fibrogenic reprogramming and MMT, highlighting adhesion-dependent signaling as a conserved pathway linking tissue remodeling to fibrotic macrophage activation and FAK as a potential therapeutic target."

Journal • Fibrosis • Immunology • Inflammation • ACTA2 • COL1A1 • ITGAL • ITGAX • ITGB2 • PTK2B • TGFB1

Targeting the FAK-Calmodulin Axis to Block Mechanobiological Tissue Factor Decryption: A Novel "Thrombo-Protective" Strategy in Cancer-Associated Thrombosis (ISTH 2026) - "Pharmacological interventions included the FAK inhibitor PF-562271 and the calmodulin antagonist Trifluoperazine (TFP). This offers a paradigm shift toward "Thrombo-protective Oncology," preventing thrombosis without the systemic bleeding risks associated with traditional anticoagulants. DOI*10.1016/j.rpth.2026.103773"

Breast Cancer • Oncology • Solid Tumor • Thrombosis

Targeting FAK Signaling to Promote Ferroptosis in Triple-Negative Breast Cancer (JBCS 2026) - "This study investigates the potential of targeting FAK signaling to dismantle these defenses and promote ferroptosis in TNBC. The effect of the FAK inhibitor PF-562271 on the sensitivity of TNBC cells to the ferroptosis inducer Erastin was assessed using cell viability assays. Our findings indicate that FAK signaling is critical for maintaining antioxidant defenses in TNBC. Pharmacological inhibition of FAK effectively sensitizes cells to ferroptosis, supporting the rationale for combining FAK inhibitors with ferroptosis inducers as a therapeutic strategy for TNBC."

Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • GPX4 • PACERR • PTGS2 • SLC7A11

Integrative spatiotemporal transcriptomics identifies a liver metastasis-related initial cell population associated with the SEMA3A-NRP1 axis in pancreatic ductal adenocarcinoma. (PubMed, J Transl Med) - "At single-cell resolution, this study characterizes the LMIC population in PDAC and implicates a CAF-associated SEMA3A-NRP1 signaling axis within their spatial and functional microenvironmental niches. These findings provide a refined conceptual framework for the development of prospective targeted strategies aimed at disrupting early microenvironmental cross-talk associated with PDAC liver metastasis."

IO biomarker • Journal • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • ACACA • CAFs • FASN • NRP1 • NRP2 • SEMA3A • YY1

Inhibition of Sclerostin Protected Against Particle-Induced Osteolysis via Activation of Wnt Signaling and Suppression of Osteoclast Function. (PubMed, J Orthop Res) - "In vitro, RSPO2 enhanced osteoclastic bone resorption, pit formation, and Pyk2 phosphorylation, which were suppressed by PF-562271. Ab-Scl modulated osteoclast function through Wnt/β-catenin-related mechanisms, potentially involving Pyk2-related pathways, thereby suppressing CoCr particle-induced osteolysis. These findings suggest that Ab-Scl is a promising pharmacological strategy for preventing aseptic loosening following joint arthroplasty."

Journal • Orthopedics • RSPO2 • TRAP

Platelet factor 4 prevents neuroinflammation and neurodegeneration in Parkinson's disease model via regulating protocadherin gamma/Pyk2 pathway. (PubMed, Brain Behav Immun) - "Pyk2 inhibitor PF-562271 administration decreased Pyk2, restored the compromised behavioral activity, neuroinflammation, and dopaminergic cell death in MPTP-injected mice. This study demonstrates that blood-borne PF4 prevents neuroinflammation and neurodegeneration in PD models by inducing Pcdhg expression and subsequently blocking Pyk2 activation. This finding highlights that Pcdhg/Pyk2 axis was a key protective molecular mechanism of PF4 in PD and the Pcdhg-Pyk2 pathway could serve as a potential drug target for PD interventions."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Inflammation • Movement Disorders • Parkinson's Disease • CDH23 • IL1B • PCDH

AI-DRIVEN PIPELINE FOR DRUG REPURPOSING: MULTI-OMICS, FUNCTIONAL EMBEDDINGS, AND STRUCTURAL EVALUATIONS (ADPD 2026) - "Importantly, novel investigational agents such as PF-562271, Glesatinib (MGCD-265), and BMS-777607 emerged as top candidates converging on FAK, PI3K–AKT, and receptor tyrosine kinase pathways. CF4DR provides a flexible and translationally relevant AI-driven framework for drug repurposing in AD. CF4DR provides a flexible and translationally relevant AI-driven framework for drug repurposing in AD. By integrating multi-omics data, functional gene embeddings, transcriptomic perturbation signatures, and chemoinformatic modeling, the pipeline systematically prioritizes candidate compounds across multiple biological and chemical dimensions. Applied to AD, and explicitly considering circadian rhythm regulators, CF4DR successfully identified top candidates with favorable systemic impact and polypharmacological profiles."

Alzheimer's Disease • CNS Disorders • Dementia

Computational identification of Cucurbitacin S and Kammogenin as bioactive focal adhesion kinase 2 inhibitors for targeted cancer therapy. (PubMed, Mol Divers) - "A comparative analysis with the reference inhibitor PF-562271 indicated the therapeutic potential of both phytochemicals, pending experimental evaluation. These findings suggest that Cucurbitacin S and Kammogenin are promising lead scaffolds for the development of plant-derived FAK2 inhibitors; however, as this is a computational, hypothesis-generating study, the results warrant further experimental validation to confirm their therapeutic potential."

Journal • Oncology

Analysis of the potential regulatory mechanism of PIEZO1 in Alzheimer's disease based on RNA sequencing. (PubMed, IBRO Neurosci Rep) - "PCA clustering revealed overall significant differences among the three groups of samples (control, AD, and PF-562271 intervention group)...Notably, the expression of PIEZO1 was higher in the AD group than in the control group. This study confirmed elevated PIEZO1 expression in astrocyte AD models, which is associated with the regulation of the extracellular matrix, cell-substrate adhesion, synaptic migration, and other related functions and pathways."

Journal • Alzheimer's Disease • CNS Disorders

Adenylosuccinate lyase (ADSL) is a pan-cancer prognostic and immune biomarker with distinct roles in hepatocellular carcinoma. (PubMed, Discov Oncol) - "ADSL holds potential as a promising prognostic marker for OS in various cancer types, particularly in HCC. Additional research is needed to confirm these findings and to understand how ADSL affects cancer development."

Biomarker • Journal • Pan tumor • Hepatocellular Cancer • Oncology • Solid Tumor

Targeting Focal Adhesion Kinase in Lung Diseases: Current Progress and Future Directions. (PubMed, Biomolecules) - "Some have progressed to clinical trials (Defactinib (Phase II), PF-562271 (Phase I), CEP-37440 (Phase I), PND-1186 (Phase I), GSK-2256098 (Phase II), BI-853520 (Phase I)), offering potential therapeutic targets for lung diseases. Emerging methodologies, such as PROTAC degraders and combination regimens, demonstrate significant potential for future research. Based on a comprehensive analysis of the relevant literature from 2015 to the present, this review briefly introduces the structure and function of FAK and discusses recent research advancements regarding FAK and its inhibitors in the context of pulmonary diseases."

Journal • Review • Acute Lung Injury • Asthma • Colorectal Cancer • Gastric Cancer • Immunology • Lung Cancer • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor • Targeted Protein Degradation

The downregulation of ubiquitin-specific peptidase 2 indicates a poor prognosis and promotes the progression of gastric cancer through focal adhesion and ECM pathway signaling. (PubMed, Sci Rep) - "The expression of USP2 was positively correlated with sensitivity to small-molecule drugs, including entinostat, SB590885, and PF-562,271. USP2 acts as a negative regulator of gastric cancer progression. Consequently, USP2 has the potential to be utilized as a therapeutic target to improve the clinical prognosis and survival rates of patients."

Journal • Gastric Cancer • Microsatellite Instability • Oncology • Solid Tumor • Targeted Protein Degradation • MSI

Evaluation of anti-liver cancer activity and anticancer mechanism of one novel small molecule compound (THY-10A62) targeting FAK pathway. (PubMed, Front Oncol) - "Efficacy was benchmarked against PF-562271...The observed reductions in FAK phosphorylation and changes in BRAF and RASGRF1 phosphorylation suggest pathway-level modulation underlying efficacy. These findings provide preliminary evidence that THY-10A62 is a potential FAK inhibitor for liver cancer therapy and warrant further studies to refine dosing, characterize pharmacokinetics/toxicity, and validate efficacy across additional HCC models."

Journal • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor • BRAF • RASGRF1

Sensitivity of Pancreatic Cancer Cell Lines to Clinically Approved FAK Inhibitors: Enhanced Cytotoxicity Through Combination with Oncolytic Coxsackievirus B3. (PubMed, Int J Mol Sci) - "In this study, we investigated the cytotoxicity of six FAKi (Defactinib, CEP-37440, VS-4718, VS-6062, Ifebemtinib and GSK2256098) used in clinical trials on five pancreatic tumor cell lines. Considering both oncolytic efficacy and the CI, the greatest enhancement in oncolytic activity was achieved when VS-4718 or CEP-37440 was combined with PD-H. These findings indicate that co-treatment with PD-H can potentiate the therapeutic activity of the selected FAKi and may represent a novel strategy to improve treatment outcomes in PDAC."

Journal • Preclinical • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

PTK2B inhibitor PF-431396 inhibits inflammatory response and apoptosis of ovarian granulosa cells by targeting AKT1 phosphorylation in premature ovarian insufficiency. (PubMed, Int Immunopharmacol) - "In this study, a rat POI model was established by intraperitoneal injection of cyclophosphamide (Cy) for 14 days...PF-431396 facilitated AKT1 phosphorylation, and the inhibitory effects of PF-431396 on GC inflammatory response and apoptosis were reversed by an AKT1 inhibitor LY294002...Additionally, it could improve Cy-induced ovarian tissue injury, inhibit inflammation and apoptosis, and elevate p-AKT1 level in ovarian tissues. Together, our results unveil that PF-431396, a PTK2B inhibitor, ameliorates ovarian dysfunction in POI through promoting AKT1 phosphorylation, suggesting that PTK2B may be a therapeutic target for POI."

Journal • Inflammation • Women's Health • PTK2B • TYK2

Identification of biomarkers associated with programmed cell death in liver ischemia-reperfusion injury: insights from machine learning frameworks and molecular docking in multiple cohorts. (PubMed, Front Med (Lausanne)) - "Finally, BMS-536924 and PF-431396 were identified as potential therapeutic agents for LIRI. This study comprehensively characterizes PCD in LIRI and identifies one core molecule, providing a new strategy for early prevention and treatment of LIRI."

Biomarker • Journal • Cardiovascular • Hepatology • Liver Failure • Reperfusion Injury • Transplantation

Pan-cancer analysis uncovered the prognostic and therapeutic value of disulfidptosis. (PubMed, NPJ Precis Oncol) - "PF-562271, EHT-1864, and IPA-3 are potential therapeutic agents targeting disulfidptosis. Collectively, this study deciphered for the first time the importance of disulfidptosis for pan-cancer and developed the DRGs Score model that can assist clinicians in accurately predicting the prognosis and guiding individualized treatment of pan-cancer patients."

Journal • Pan tumor • Genito-urinary Cancer • Kidney Cancer • Oncology • Solid Tumor

Focal adhesion kinase promotes aerobic glycolysis in hepatic stellate cells via the cyclin D1/c-Myc/MCT-1 pathway to induce liver fibrosis. (PubMed, Sci Rep) - "LX-2 cells showed diminished migration, proliferation, and aerobic glycolysis after PF562271 intervention. FAK promotes aerobic glycolysis in LX-2 cells through the cyclin D1/c-Myc/MCT-1 pathway, thereby increasing liver fibrosis."

Journal • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • CCND1 • MYC • SLC16A1 • TGFB1

Design, Synthesis, and Biochemical Evaluation of Novel MLK3 Inhibitors: A Target Hopping Example. (PubMed, J Med Chem) - "In a target hopping example we started with the focal adhesion kinase (FAK) inhibitor PF-431396 (10), which shows off-target activity toward MLK3...Furthermore, we achieved a dramatic shift in selectivity from FAK to MLK3. Here we present a new chemical class of MLK3 inhibitors, including our lead compound 37 with an outstanding IC50 value of <1 nM in a biochemical MLK3 assay while simultaneously exhibiting kinome-wide selectivity."

Journal • Oncology • MAP3K11

Prognosis and immunotherapeutic implications of molecular classification of cervical cancer based on immunophenoscore-related genes. (PubMed, J Biomol Struct Dyn) - "cluster2 had higher immune cell infiltration levels and better prognosis, with greater sensitivity to Cyclopamine, Imatinib, MG-13, Paclitaxel, PHA-665752, Rapamycin, Sorafenib, Sunitinib, and VX-680. In contrast, cluster3 had higher TTN and PIK3CA mutations and greater sensitivity to AZ628, Dasatinib, Doxorubicin, HG-6-64-1, JQ12, Midostaurin, PF-562271, TAE684, and WH-4-023. In conclusion, we developed a feasible risk score model based on IPS-related genes for cervical cancer prognosis and identified potential drugs for different cervical cancer subtypes."

IO biomarker • Journal • Cervical Cancer • Oncology • Solid Tumor • PD-L2 • PIK3CA

The mechanism of L1 cell adhesion molecule interacting with protein tyrosine kinase 2 to regulate the focal adhesion kinase-growth factor receptor-bound protein 2-son of sevenless-rat sarcoma pathway in the identification and treatment of type I high-risk endometrial cancer. (PubMed, Cytojournal) - "L1CAM expression was regulated using lentiviruses designed for either overexpression or interference, and PTK2/focal adhesion kinase (FAK) signaling was inhibited with PF431396...By upregulating PTK2 and its encoded protein FAK, L1CAM was found to promote tumor progression and increase the activation of the FAK-GRB2-SOS-RAS pathway. These findings establish L1CAM and PTK2 as reference genes for poor prognostic prediction in EC and as targets for EC therapy, providing a valuable basis for distinguishing between benign and malignant endometrial conditions and justifying the necessity of targeted therapeutic approaches."

Journal • Preclinical • Endometrial Cancer • Oncology • Sarcoma • Solid Tumor • L1CAM • MMP9 • TYK2

Prognostic value of anoikis-related genes revealed using multi-omics analysis and machine learning based on lower-grade glioma features and tumor immune microenvironment. (PubMed, Heliyon) - "The high-risk group was characterized by a "cold" tumor microenvironment (TME), a lower IDH1 mutation rate (61.7 % vs. 91.4 %), a higher TP53 mutation rate (53.7 % vs. 38.9 %), and greater sensitivity to targeted therapies such as QS11 and PF-562271...The robustness of this prognostic model was further validated through internal cross-validation and across three external cohorts. The evidence from our research suggests that ARGs could potentially serve as reliable indicators for evaluating immunotherapy effectiveness and forecasting clinical results in patients with LGG."

IO biomarker • Journal • Machine learning • Brain Cancer • CNS Tumor • Glioma • Oncology • Solid Tumor • IDH1 • TP53

Prognostic model for hepatocellular carcinoma based on necroptosis-related genes and analysis of drug treatment responses. (PubMed, Heliyon) - "Notable, Bleomycin, Obatoclax. Mesylate, PF.562271, PF.02341066, QS11, X17. AAG, and Bl. D1870 exhibited significantly different sensitivities in different subtypes, providing references for clinical practice in HCC patients."

IO biomarker • Journal • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Liver Cancer • Oncology • Solid Tumor

Enhanced phagocytosis associated with multinucleated microglia via Pyk2 inhibition in an acute β-amyloid infusion model. (PubMed, J Neuroinflammation) - "To assess the phagocytic capacity of multinucleated microglia and its implications for brain debris clearance, we induced their formation by inhibiting Pyk2 activity using the pharmacological inhibitor PF-431396, which triggers cytokinesis regression...These results suggest that Pyk2 inhibition can modulate microglial functions, potentially reducing neuroinflammation and aiding in the clearance of neurodegenerative disease markers. This highlights Pyk2 as a promising target for therapeutic intervention in neurodegenerative diseases."

Journal • Alzheimer's Disease • CNS Disorders • Infectious Disease • Inflammation • LAMP1

Difference in Contractile Mechanisms between the Early and Sustained Components of Ionomycin-Induced Contraction in Rat Caudal Arterial Smooth Muscle. (PubMed, Biol Pharm Bull) - "On the other hand, a ROCK inhibitor, HA-1077 (3 µM), and Pyk2 inhibitors, sodium salicylate (10 mM) and PF-431396 (3 µM), suppressed only the sustained phase of ionomycin-induced contraction...Early or sustained increase of ionomycin-induced 20 kDa light chain of myosin (LC20) phosphorylation was inhibited by each inhibitor in a manner similar to the attenuation of contraction. These results indicate that the early phase of ionomycin-induced contraction is mediated by MLCK activation by [Ca2+]i elevation, whereas the sustained phase of ionomycin-induced contraction involves RhoA/ROCK activation and inhibition of myosin light chain phosphatase (MLCP) through CaM-independent Pyk2 activation by [Ca2+]i elevation."

Journal • Preclinical • MYLK • RHOA • TYK2