Turalio (pexidartinib) / Daiichi Sankyo - LARVOL DELTA

Modulation of brain functions by glial reset (CINP-AsCNP 2025) - " Microglial reset was enabled by turning ON/OFF of CSF1R antagonists (PLX5622 or PLX3397). Microglia can be easily, safely, and reproducibly replaced by turning ON/OFF of CSF1R antagonists (Reset) and by microglia transplantation combined with the Reset and microglia intranasal transplantation. Microglial abnormalities have been observed in the brains of various animal models of brain diseases. Removal of these microglia alone does not necessarily result in improvement of the disease state."

Autism Spectrum Disorder • CNS Disorders • Genetic Disorders • Inflammation • Psychiatry • Rare Diseases

Effect of developmental deficits in ventral hippocampal excitatory and inhibitory neurons in schizophrenia-relevant phenotypes in mice (CINP-AsCNP 2025) - "Systemic administration of a microglia depleting drug PLX 3397 significantly rescued Y-maze deficit in CaMKII ablated mice. Our data suggest that adult behavioral vulnerabilities to juvenile VH disruptions are cell-type dependent. VH excitatory/inhibitory deficits, interacting with periadolescent maturational processes such as PFC microglial activity, may play complementary roles in determining schizophrenia-related phenotypes."

Preclinical • CNS Disorders • Infectious Disease • Mood Disorders • Psychiatry • Schizophrenia

Vimseltinib: A novel colony stimulating factor 1 receptor (CSF1R) inhibitor approved for treatment of tenosynovial giant cell tumors (TGCTs). (PubMed, Intractable Rare Dis Res) - "As the second-in-class CSF1R inhibitor approved for TGCTs, vimseltinib exhibits enhanced selectivity for CSF1R over pexidartinib, the first-in-class agent, suggesting potential translational benefits in safety profiles. The clinical utility of vimseltinib is anticipated to be further elucidated by real-world evidence and expanded clinical evaluations."

Journal • Giant Cell Tumor of Bone • Oncology • Tenosynovial Giant Cell Tumor

Pediatric patients with tenosynovial giant cell tumor: Real-world results from an observational registry. (ASCO 2025) - "Systemic therapies (i.e., imatinib, nilotinib, pexidartinib) were prescribed infrequently to pediatric patients with D-TGCT (17.2%). This real-world analysis highlights the significant disease burden of pediatric TGCT, as compared to adults, which severely affecting their quality of life. The reliance on surgical treatment and underuse of multidisciplinary care emphasizes the unmet need for provider education and treatment advancements tailored to this population. Greater efforts to develop systemic therapies specific to pediatrics are warranted to reduce recurrence rates and improve quality of life."

Clinical • Real-world • Real-world evidence • Giant Cell Tumor of Bone • Oncology • Orthopedics • Pain • Pediatrics • Tenosynovial Giant Cell Tumor

Pexidartinib Inhibits Macrophage Senescence Through Glycolysis in Periodontitis Microenvironment. (PubMed, Int Dent J) - "Our findings indicate that PLX3397 alleviates periodontal tissue inflammation by inhibiting macrophage senescence via glycolytic modulation, offering potential for immune-regulatory therapies in periodontitis management."

Journal • Dental Disorders • Inflammation • Periodontitis

Emerging strategies for targeting tumor-associated macrophages in glioblastoma: A focus on chemotaxis blockade. (PubMed, Life Sci) - "Additionally, we discuss the preclinical and clinical evidence surrounding key inhibitors, such as PLX3397, AMD3100, and Crizotinib, which have shown promise in reprogramming TAMs and improving treatment outcomes in GBM. While these strategies offer hope for overcoming some of the challenges of GBM therapy, the review also addresses the limitations and obstacles in clinical translation, emphasizing the need for further research and the development of combination therapies to achieve sustained therapeutic benefit."

Journal • Review • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • CSF1R • CXCL12 • CXCR4

Colony-stimulating factor-1 receptor inhibitor augments osimertinib-induced anti-tumor immunity via suppression of macrophages in lung cancer harboring EGFR mutation. (PubMed, Mol Cancer Ther) - "We previously reported that gefitinib induces CD8⁺ T cell-related tumor immunity in a genetically engineered mouse model (GEMM)...Combining osimertinib with the colony-stimulating factor-1 receptor (CSF1R) inhibitor pexidartinib reduced CD206⁺ macrophages and enhanced the efficacy of osimertinib...M2-like macrophages may contribute to immune tolerance of persister cancer cells against EGFR-TKI-induced tumor immunity. A clinical trial evaluating combined osimertinib and CSF1R inhibitor therapy is warranted for Egfr-mutated lung cancer."

IO biomarker • Journal • Lung Cancer • Oncology • Solid Tumor • Transplantation • CD8 • EGFR • LAMP2 • MRC1 • PD-1

TURALIO® Risk Evaluation and Mitigation Strategy (tREMS) program: 5-year retrospective hepatic safety assessment. (PubMed, Future Oncol) - "The tREMS Program effectively mitigates the risk of hepatotoxicity through careful monitoring and early intervention. Pexidartinib remains a viable treatment option for TGCT when managed according to recommended guidelines."

Journal • Retrospective data • Giant Cell Tumor of Bone • Hepatology • Liver Failure • Oncology • Tenosynovial Giant Cell Tumor

Pexidartinib impairs liver mitochondrial functions causing cell death in primary human hepatocytes at clinically relevant concentrations. (PubMed, Biochem Biophys Res Commun) - "Importantly, the detrimental effects noted above occurred at pexidartinib concentrations of 0.5- to 2.5-fold of the human peak blood concentration (Cmax) achieved with the recommended therapeutic dose. These data suggest that mitochondrial injury and hepatocyte toxicity are involved in the mechanism of pexidartinib-induced hepatotoxicity."

Journal • Hepatology • Renal Cell Carcinoma

Medical Management of Tenosynovial Giant Cell Tumor. (PubMed, Curr Oncol Rep) - "For an alternative to surgery, the CSF1R inhibitors pexidartinib and vimseltinib are approved in the United States for TGCT, and other CSF1R inhibitors are in clinical development...The potential risks and benefits of available treatments should be carefully considered in collaboration with a bone tumor-experienced, multidisciplinary team to determine the best course of care. Increased D-TGCT awareness and support through patient advocacy groups have helped to reshape the patient journey."

Journal • Review • Giant Cell Tumor of Bone • Oncology • Osteosarcoma • Solid Tumor • Tenosynovial Giant Cell Tumor

Macrophage Polarization, Inflammatory Monocytes, and Impaired MDSCs are Associated with Murine and Human Immune Aplastic Anemia. (PubMed, J Leukoc Biol) - "CSF-1R inhibition with the small molecule PLX3397 intensified BMF in CByB6F1 mice, enhancing inflammation and macrophage polarization toward the pro-inflammatory M1 phenotype...In contrast, the JAK-inhibitor baricitinib attenuated BMF, promoting M2 macrophage polarization, and decreasing CD8+ T cell infiltration of bone marrow...These findings highlight the role of myeloid-derived cells in BMF and suggest that M1 macrophages, with defective MDSC function, contribute to disease pathogenesis and progression. Targeting macrophage polarization or MDSCs offers alternative therapeutic strategies in immune-mediated BMF."

Journal • Preclinical • Anemia • Aplastic Anemia • Hematological Disorders • Inflammation • CD8 • ITGAM

CSF1R Inhibitor Treatment Facilitates Engraftment of Hematopoietic Stem Cell-Derived Microglia-Like Cells in Nonhuman Primates (ASGCT 2025) - "Recent work in murine models has demonstrated that MLC engraftment can be enhanced using gene-modified, autologous HSCT (auto-HSCT) paired with depletion of endogenous microglia by CSF1R inhibitors such as Pexidartinib (PLX)...Ways to further enhance MLC engraftment and functionalize MLCs with gene engineering strategies will pave the way for the application of these technologies for a range of neurotrophic disorders from LSDs to neurodegenerative diseases. Disease Focus of Abstract:Central Nervous System Disorders"

Bone Marrow Transplantation • CNS Disorders • Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases • Transplantation

Myeloid Cell Replacement Therapy Improves Function in Friedreich Ataxia Mice by Intercellular Mitochondrial Transfer (ASGCT 2025) - "To achieve this, we performed BMT using the human FXN YAC transgenic mouse model (YG8s800) carrying over 800 GAA repeats, following a conditioning regimen with Busulfan and PLX3397 to enhance the engraftment of bone marrow-derived cells in CNS tissues. This study serves as a foundational step toward developing treatments for FA and other mitochondrial dysfunction-related disorders. Disease Focus of Abstract:Mitochondrial Disease"

Preclinical • Ataxia • Bone Marrow Transplantation • Friedreich ataxia • Metabolic Disorders • Movement Disorders • Solid Tumor • CHCHD1 • IGFBP2 • PTGDS

Hematopoietic Stem Cell Transplantation with Enhanced Brain Conditioning Corrects Progranulin Deficiency in mouse models (ASGCT 2025) - "This enhanced conditioning combines busulfan with PLX3397, a CNS-penetrant inhibitor of the Colony-stimulating factor 1 receptor (CSF1R). These findings lay the foundation for advancing these approaches toward clinical application. Disease Focus of Abstract:Inherited Neurological Disorders"

Preclinical • Alzheimer's Disease • Bone Marrow Transplantation • CNS Disorders • Dementia • Frontotemporal Lobar Degeneration • Gene Therapies • Graft versus Host Disease • Immunology • Transplantation • GRN • PTPRC

Oleoylethanolamide exerts neuroprotection following ischemic stroke through microglial PPARα signal. (PubMed, Int Immunopharmacol) - "We found that the ablation of microglia by the PLX3397 dramatically diminishes the therapeutic effects of OEA in ischemic stroke...Therefore, we found that OEA exerts its therapeutic effects against ischemic stroke through microglia PPARα signal. Our findings provide new evidence for the therapeutic potential of OEA in ischemic stroke, further indicating that OEA may become a novel candidate for ischemic stroke therapy."

Journal • Cardiovascular • Inflammation • Ischemic stroke • OCLN • PPARA • TJP1

Microglia promote bystander activated T cell-mediated neurological disease during viral infection (IMMUNOLOGY 2025) - "Interestingly, depletion of brain-resident microglia using the drug PLX3397 also prevented development of neurological disease...Overall, we have identified a novel mechanism where microglia promote bystander activation and function of CD8+ T cells neurological disease. Our findings reveal several strategies for further investigation of treatments for virus-induced neurological diseases.Keywords: Animals Rodent; Cells Monocytes/Macrophages T Cells; Infections Viral; Processes Neuroimmunology"

CNS Disorders • Infectious Disease • CD8 • NKG2D

Phase II Study of Pexidartinib Plus Sirolimus in Unresectable Malignant Peripheral Nerve Sheath Tumors Identifies M2 Macrophage Activation. (PubMed, JCO Oncol Adv) - "Further studies of combination of pexidartinib and sirolimus and/or immunotherapy should be performed in the subset of patients with advanced MPNST with an immune-rich TME."

Journal • P2 data • Brain Cancer • Genetic Disorders • Hematological Disorders • Infectious Disease • Leukopenia • Neurofibromatosis • Neurofibrosarcoma • Novel Coronavirus Disease • Oncology • Sarcoma • Solid Tumor

Brain-wide microglia replacement using a nonconditioning strategy ameliorates pathology in mouse models of neurological disorders. (PubMed, Sci Transl Med) - "This approach leverages three cycles of microglial depletion using the colony stimulating factor 1 receptor (CSF1R) inhibitor PLX3397, creating an optimal window for efficient engraftment of exogenous microglia...Similarly, in an Alzheimer's disease (AD)-related amyloid mouse model carrying the triggering receptor expressed on myeloid cells 2 (Trem2) R47H mutation, our transplantation strategy rescued microglial dysfunction and mitigated AD-related pathology. Overall, our study introduces TCMDT as a practical, efficient, and safe approach for microglia replacement, suggesting therapeutic potential for treating neurological disorders associated with microglial dysfunction."

Journal • Preclinical • Alzheimer's Disease • Bone Marrow Transplantation • CNS Disorders • Genetic Disorders • Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases • Transplantation • Vascular Neurology • TREM2

Microglia specific Csf1r haploinsufficiency induces depressive-like behaviors by promoting NLRP6/caspase-1 signaling in mice. (PubMed, Brain Behav Immun) - "Blockade of CSF1R signaling with PLX3397 resulted in significant amelioration of depressive symptoms and restoration of normal microglial morphology and function. Pharmacological inhibition of caspase-1 using VX-765 improved depressive-like behaviors, as well as microglial function. Taken together, our findings delineate a causal relationship between microglial Csf1r haploinsufficiency-induced activation of the NLRP6/caspase-1 signaling pathway and the manifestation of depressive-like behaviors in ALSP mice."

Journal • Preclinical • CNS Disorders • Depression • Psychiatry • CSF1R • NLRP3 • NLRP6

Turning up the heat: nanoimmunotherapy transforming outcomes in breast cancer treatment (AACR 2025) - "POx-Man nanovaccine combined with Pexidartinib restricted the MC38 tumor growth and synergized with PD-1 blockade, controlling MC38 and CT26 tumor growth and survival. This data was further validated in B16F10-bearing mice, a highly aggressive and poorly immunogenic melanoma mouse model for immunotherapy studies.This innovative approach discloses the synergy among the targeted cancer nanovaccine and immune modulatory and checkpoint therapies (αCSF-1R and αPD-1) within the immunosuppressive TME, which overall outcome may constitute a promising nanotechnology-enhanced immunotherapy for solid cancer patients."

IO biomarker • Breast Cancer • Melanoma • Oncology • Solid Tumor • CD8 • MRC1 • TGFB1

Leveraging chemo-immunotherapy to remodel the tumor microenvironment and enhance treatment efficacy in osteosarcoma lung metastases (AACR 2025) - "Gemcitabine (GMT), has shown limited efficacy in relapsed OSLM when administered systemically...To address this gap, we propose a novel strategy combining inhaled GMT with colony-stimulating factor-1 receptor inhibitors (CSF-1Ris); pexidartinib (PLX-3397), that target tumor-associated macrophages (TAMs), both delivered locally to lungs via PA...We also developed a 3D spheroid model with the relevant immune-cells that mimic key aspects for the in vivo model. These studies help us identify clinically translatable combination therapies for OSLM as both GMT and PLX are approved clinically."

Biomarker • Clinical • IO biomarker • Tumor microenvironment • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • IL4

Targeting interactions between tumor-associated macrophages and tumor cells to enhance chemotherapy response in a resection model of triple-negative breast cancer (AACR 2025) - "We selected pexidartinib (PLX) as CSF-1Ri given its translational potential (FDA approved) and gemcitabine (GEM) as chemotherapy, given its immunomodulatory effects. Triple therapy also had the greatest prolongation of MFS and OS (prolonged by 30% and 31% compared to GEM, respectively). Thus, the therapeutics investigated led to a remodeling of the TNBC TME towards a favorable phenotype, leading to enhanced chemotherapy efficacy and prolonged survival."

Tumor cell • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CD47 • SIRPA

Development of a CSF-1Ri liposomal formulation using a continuous manufacturing approach and design of experiments (DOE) (AACR 2025) - "PLX-3397 (PLX), an FDA-approved colony-stimulating factor-1 receptor inhibitor (CSF-1Ri), targets tumor-associated macrophages (TAMs) in solid tumors, offering a promising strategy to support standard of care in OSLM...In vitro experiments with RAW 264.7 macrophages polarized to an M2-like phenotype showed that L-PLX reduced M2-like phenotype, confirming its potential to modulate TAM phenotypes while retaining therapeutic activity. These results highlight L-PLX as a promising candidate for OSLM therapy."

Oncology • Osteosarcoma • Sarcoma • Solid Tumor • CSF1R

Vimseltinib (Romvimza) for tenosynovial giant cell tumor. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal • Giant Cell Tumor of Bone • Oncology • Tenosynovial Giant Cell Tumor

Depletion of HSP60 in Microglia Leads to Synaptic Dysfunction and Depression-Like Behaviors Through Enhanced Synaptic Pruning in Male Mice. (PubMed, CNS Neurosci Ther) - "HSP60 deletion in microglia leads to overactivation of microglia, impaired synaptic function, and depression-like behaviors, highlighting the importance of microglial homeostasis in mood regulation and the potential therapeutic role of microglial modulation."

Journal • Preclinical • CNS Disorders • Depression • Mood Disorders • Psychiatry • CD68 • CD86 • CX3CR1 • CYBB • DLG4 • HSPD1 • Napsin A