Turalio (pexidartinib) / Daiichi Sankyo - LARVOL DELTA

LONG-TERM EFFICACY AND SAFETY OF PEXIDARTINIB IN PATIENTS WITH TENOSYNOVIAL GIANT CELL TUMOR: RESULTS FROM THE PHASE 3 ENLIVEN STUDY (CTOS 2022) - No abstract available

Clinical • P3 data • Giant Cell Tumor of Bone • Immunology • Oncology • Tenosynovial Giant Cell Tumor

Microglia Ablation and Downstream Effects in the Cerebrospinal Fluid Proteome. (PubMed, Proteomics) - "In contrast to the robust changes in microglial and neuronal proteins, there was no evidence of astrogliosis after microglia ablation as determined by proteome analysis and brain histology. These observations are crucial for interpreting changes to the CSF proteome in relation to neuroinflammatory changes in neurological diseases."

Journal • CNS Disorders • CX3CL1 • IL34

Dynamics of Tumor Progression in Glioblastoma Patients through Longitudinal Profiling (EANO 2026) - "Analysis of matched primary and recurrent samples from two IDH wildtype glioblastoma patients revealed highly similar drug sensitivity and resistance patterns, including sensitivity to Pexidartinib and Pazopanib and resistance to Panobinostat and Selinexor, suggesting convergent therapeutic response profiles. In a subset of patients, recurrent glioblastomas may undergo convergent adaptation, characterized by shared drug responses and metabolic changes that cannot be fully explained by genomic alterations, highlighting the role of non-genetic mechanisms. Longitudinal profiling can reveal the dynamics of therapy resistance and identify targetable vulnerabilities and will may further support personalized treatment strategies especially for recurrent tumors."

Clinical • Astrocytoma • Brain Cancer • Glioblastoma • Oncology • Solid Tumor

Results from Phase 1 Extension Study Assessing Pexidartinib Treatment in 6 cohorts with Solid Tumors including TGCT, and Abnormal CSF1 Transcripts in TGCT. (PubMed, Clin Cancer Res) - "These results offer insight into outcome patterns in cancers whose biology suggests use of a CSF1R inhibitor. Pexidartinib results in tumor regression in TGCT patients, providing prolonged control with an acceptable safety profile."

Clinical • Journal • P1 data • Giant Cell Tumor of Bone • Immunology • Oncology • Pain • Solid Tumor • Tenosynovial Giant Cell Tumor • CSF1 • FLT3

CORR Insights®: Pexidartinib Provides Modest Pain Relief in Patients With Tenosynovial Giant Cell Tumor: Results From ENLIVEN. (PubMed, Clin Orthop Relat Res) - No abstract available

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

Evaluation of 18F-FPPA as a Positron Emission Tomography Radioligand for Imaging CSF1R in LPS-Induced Rat Model of Neuroinflammation. (PubMed, Mol Pharm) - "A decreased uptake also was observed in cold 19F-FPPA, BLZ945, and PLX3397 blocking groups (P 0.05). The in vivo imaging and immunohistochemical results confirmed the specific uptake of 18F-FPPA by targeting CSF1R on microglia in inflamed tissues. Overall, our findings demonstrated that 18F-FPPA had great potential as a promising tracer for the imaging of neuroinflammatory diseases, while its unique binding profile also provides insights into CSF1R-targeted ligand development."

Journal • Preclinical • Gastrointestinal Disorder • Inflammation • CSF1R

Vaccination against extracellular vimentin boosts tumor immune cell infiltration and improves survival of glioma-bearing mice (EANO 2026) - "Therapeutic vaccination was tested in the CT2A model in combination with a single dose (5 Gy) of local radiotherapy, a chemotherapeutic agent (CCNU) or a colony stimulating factor 1 receptor (CSF-1R) inhibitor PLX3397... Targeting extracellular vimentin via vaccination reshapes the tumor microenvironment and improves survival of glioma-bearing mice. Our findings emphasize an important role of extracellular vimentin in the growth and progression of gliomas and provide a method targeting this vulnerability that may become a novel therapeutic option for the treatment of patients with glioblastoma."

Immune cell • Preclinical • Brain Cancer • Glioblastoma • Glioma • Oncology • Solid Tumor • VIM

Assessing the effectiveness of the TURALIO (pexidartinib) risk evaluation and mitigation strategy program: patient knowledge, attitudes, and behavior survey (2020-2024). (PubMed, Patient Relat Outcome Meas) - "Demonstrated understanding of KRMs remained generally stable despite evolving patient demographics and treatment duration over time. Across KAB Survey waves, patients receiving TURALIO demonstrated sustained knowledge of hepatotoxicity risk and monitoring requirements supporting the effectiveness of the tREMS program in ensuring the safe real-world use of pexidartinib."

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

CSF1R⁺ myeloid cells mediate resistance to CAR-T-cell therapy in lung cancer brain metastases (EANO 2026) - "CSF1R inhibition with PLX3397 further enhanced CAR-T cell accumulation, increased CAR-T/TAM contact frequency, and improved CAR-T cell persistence, resulting in delayed tumor progression and prolonged survival compared to either monotherapy... These findings identify TAM/M-driven immunosuppression as a central barrier to CAR-T cell efficacy in brain metastases and demonstrate that CSF1R-mediated myeloid reprogramming can overcome this limitation. By shifting the tumor microenvironment toward an immunopermissive state, CSF1R inhibition enhances CAR-T cell persistence, functionality, and therapeutic efficacy. This work establishes myeloid-targeted modulation as a key strategy to unlock CAR-T cell activity in solid tumors of the central nervous system."

CAR T-Cell Therapy • Brain Cancer • Lung Cancer • Oncology • Solid Tumor • CD8 • CSF1R

WTAP Transcriptional Suppression by KLF9 Drives Osteoclastogenesis via M6A-Mediated Regulation of CSF1R Signaling in Estrogen-Deficient Osteoporosis. (PubMed, Adv Sci (Weinh)) - "Therapeutically, targeting this axis via AAV-mediated Wtap overexpression or pharmacological CSF1R inhibition with pexidartinib effectively ameliorates bone loss in osteoporotic mice. Our findings elucidate a previously unrecognized epitranscriptomic mechanism controlling osteoclastogenesis and highlight its therapeutic potential for pathological bone resorption."

Journal • Osteoporosis • Rheumatology • CSF1R • KLF9 • WTAP • YTHDF2

A scRNA-seq-guided gelsolin-functionalized gelatin methacryloyl platform integrating structural support and immunomodulation for osteoarthritis repair. (PubMed, Int J Biol Macromol) - "We developed Gelsolin-Gelma@PLX3397 (GGP) hydrogel successfully mimicked the viscoelastic properties of the natural extracellular matrix (ECM) while providing sustained, localized delivery of both structural proteins and small-molecule inhibitors which were identified in scRNA-seq...Our findings demonstrate that the GGP hydrogel provides a synergistic "structural support and molecular modulation" strategy. By re-engineering the joint's cellular landscape based on scRNA-seq-derived targets, this smart biomaterial platform offers a promising therapeutic avenue for the functional recovery and long-term repair of osteoarthritic joints."

Journal • Immunology • Inflammation • Osteoarthritis • Pain • Rheumatology • GSN

Clodronate Liposome effectively Mitigates Chemically-Induced Retinal Pigment Epithelium Toxicity. (PubMed, Exp Eye Res) - "Given the critical roles of both resident microglia and peripheral macrophages in retinal degenerative diseases, this study systematically evaluated the protective effects of minocycline, PLX3397, and clodronate liposomes in sodium iodate (NaIO3)- and N-methyl-N-nitrosourea (MNU)-induced retinal degeneration models. In contrast, systemic depletion of peripheral macrophages using clodronate liposomes significantly alleviated fundus atrophy, partially preserved visual function, and increased photoreceptor and retinal pigment epithelium (RPE) survival in the NaIO3 model, but conferred no protection in the MNU model. These findings suggest that clodronate liposomes exert model-dependent protection, likely through modulation of peripheral macrophage-mediated RPE toxicity following chemical exposure."

Journal • Ophthalmology

Dual inhibition of CSF-1R and IDO modulates the fibrotic and immunosuppressive tumor microenvironment in pancreatic ductal adenocarcinoma. (PubMed, Front Immunol) - "In high fibrotic, CSF1RHigh KPC4662.5 tumors, dual targeting of CSF-1R and the immunosuppressive molecule indoleamine 2,3-dioxygenase (IDO), via PLX3397 and IDO-targeting Salmonella, respectively, significantly reduced tumor burden but showed no combination advantage in CSF1RLow tumors...This combination therapy altered intratumoral immune cell composition by decreasing PMN-MDSCs and increasing effector T cell subsets. These findings identify tumor fibrosis and CSF-1R expression as potential biomarkers of response to combined CSF-1R and IDO inhibition and support biomarker-guided immunotherapeutic strategies in PDAC."

Biomarker • IO biomarker • Journal • Fibrosis • Immunology • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CSF1R • TGFB1

CX3CR1+ macrophages aggravate doxorubicin-induced cardiomyopathy by impairing cardiac mitophagy via the CSF1R-PARP1-IL1B axis. (PubMed, Autophagy) - "Notably, the use of the CSF1R inhibitor PLX3397 or an IL1B-neutralizing antibody effectively halted these pathological processes and significantly improved cardiac function. In summary, this study unveils a novel mechanism through which Cx3cr1+ macrophages regulate cardiomyocyte function via the CSF1R-PARP1-IL1B-mitophagy signaling axis, providing a new theoretical foundation and intervention strategy for doxorubicin-induced cardiomyopathy targeted therapy.Abbreviations: BMDM: bone marrow-derived macrophages; CKMB: creatine kinase MB isoenzyme; CSF1R: colony stimulating factor 1 receptor; csf1r-cKO: csf1r conditional knockout; DIC: doxorubicin-induced cardiomyopathy; DOX: doxorubicin; HE: hematoxylin and eosin; HW:TL: heart weight:tibial length; LDH: lactate dehydrogenase; MAP1LC3/LC3: microtuble-associated protein 1 light chain 3; NPPA: natriuretic peptide type A; PI: propidium iodide; PYCARD/ASC: PYD and CARD domain containing; TNNT2/cTnT: troponin T2, cardiac; WGA:..."

Journal • Cardiomyopathy • Cardiovascular • Targeted Protein Degradation • CSF1R • CX3CR1 • IL1B • NEDD4 • PARP1 • PYCARD

Targeting the MAPK/ERK Signaling Pathway: Mechanistic Analysis of Pexidartinib in Overcoming Adriamycin Resistance in Breast Cancer. (PubMed, Exp Cell Res) - "exidartinib overcomes adriamycin resistance in breast cancer through multi-target effects, providing a basis for clinical trials."

Journal • Breast Cancer • Oncology • Solid Tumor • Women's Health

7-azaindole as privileged scaffold: Advances in drug design and structural modification. (PubMed, Med Chem Res) - "Approved drugs such as vemurafenib, pexidartinib, and venetoclax exemplify its successful translation from fragment to drug. This review comprehensively summarizes medicinal chemistry advances based on the 7-azaindole scaffold from 2020 to 2026, and critically consolidates SAR trends, pinpoints the most frequently successful substitution vectors, and dissects recent clinical failures. It aims to provide a reference for the future development of novel 7-azaindole-based therapeutics."

Journal • Review • Infectious Disease • Oncology

Integrative transcriptomics, machine learning, and molecular docking derive a DAM-like macrophage signature for risk stratification and therapeutic nomination in glioblastoma. (PubMed, Comput Biol Chem) - "Computational pharmacogenomic profiling suggests that this signature may predict intrinsic resistance to temozolomide but high sensitivity to CSF1R and TGF-β pathway inhibitors, and molecular docking simulations provide structural support for candidate drug-target interactions. These in silico findings identify pexidartinib and galunisertib as candidate agents for further preclinical evaluation targeting the DAM-like metabolic state. This study provides a computational framework for dissecting macrophage heterogeneity and nominating candidate therapeutic strategies that require further experimental validation in glioblastoma."

Journal • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • CCL2 • CSF1R • MMP14 • MMP9 • TGFB1

Small Extracellular Vesicles From Cardiomyocytes Activate Microglia Aggravating HFpEF. (PubMed, Circ Res) - "Microglial depletion with PLX3397 suppressed sympathetic activity and improved cardiac dysfunction in HFpEF...Our study reveals that HFpEF prompts cardiomyocytes to release sEVs enriched with miR-200c-3p, leading to hypothalamic inflammation and evoking sympathetic outflow, which in turn exacerbates cardiac dysfunction. Focusing on sEV-mediated communication between cardiomyocytes and microglia may offer a new therapeutic approach for HFpEF."

Journal • Cardiovascular • Congestive Heart Failure • Heart Failure • Inflammation • DUSP1 • MIR200C

PLX3397 Reshapes Hepatic Lipid Metabolism Independent of Microglial Depletion. (PubMed, Neurosci Bull) - "Colony-stimulating factor 1 receptor (CSF1R) inhibitors, such as PLX5622 and PLX3397 (pexidartinib), are widely used for in vivo microglial depletion and for investigating microglial functions and therapeutic potential. By uncovering previously unrecognized peripheral effects of PLX3397, our findings identify brain-periphery interactions as a potential source of confounding in studies of microglial function. These results suggest that systemic metabolic effects should be carefully considered when interpreting neural or behavioral phenotypes in pharmacological microglia depletion paradigms."

Journal • Anesthesia • CNS Disorders • Genetic Disorders • Metabolic Disorders • Obesity • Psychiatry

Zika virus infection induces a persistent accumulation of Alzheimer's disease-like Tau phosphorylation in adult immunocompetent mice in association with memory and social behavior impairments. (PubMed, Acta Neuropathol Commun) - "The role of microglia on ZIKV-induced pTau was investigated by partially depleting microglial cells using PLX3397 (PLX)...At 30 dpi, pTau progressed independently of infection and inflammation, positively correlated to PLX-susceptible Apoe gene expression in association with short-term memory defects. These results shed light on how brain viral infections, which are a major concern for public health, drive pTau accumulation and propagation in link with memory impairment and social behavior alterations laying the groundwork for potential new therapeutic treatments."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Infectious Disease • Inflammation • APOE

Galectin-9-driven immune evasion constrains radiotherapy-induced systemic antitumor immunity. (PubMed, J Immunother Cancer) - "Our findings establish RT-induced Gal-9 as a novel dual myeloid/T-cell immune checkpoint restricting abscopal responses. Gal-9 blockade represents a promising strategy to potentiate radiotherapy against metastatic disease, defining a therapeutic paradigm distinct from conventional checkpoint inhibitors."

Journal • Colorectal Cancer • Lung Cancer • Oncology • Solid Tumor • CD8 • HAVCR2 • IFNAR1 • LGALS9 • STING

Microglia-Dependent BDNF Signaling in the Dentate Gyrus Underlies the Antidepressant Effects of Gardiquimod, a Toll-Like Receptor 7 Agonist, in Chronically Stressed Mice. (PubMed, Neurochem Res) - "Mechanistically, the antidepressant effects of GDQ were abolished by both pharmacological inhibition (minocycline) and genetic depletion (PLX3397) of microglia, highlighting the necessity of these cells. Each intervention abolished the behavioral effects of GDQ. Together, these findings identify GDQ as a promising candidate for antidepressant development and highlight the restoration of microglia-supported BDNF signaling in the dentate gyrus as a key mechanism underlying TLR7-mediated mood regulation."

IO biomarker • Journal • Preclinical • CNS Disorders • Depression • Psychiatry • NTRK2

A Study of Pexidartinib in Tenosynovial Giant Cell Tumor in Japan (clinicaltrials.gov) - P2 | N=9 | Completed | Sponsor: Daiichi Sankyo Co., Ltd. | Active, not recruiting ➔ Completed

Trial completion • Giant Cell Tumor of Bone • Oncology • Tenosynovial Giant Cell Tumor

PLX3397: A Study of the Efficacy and Safety of Pexidartinib in Adult Subjects With TGCT (clinicaltrials.gov) - P3 | N=40 | Active, not recruiting | Sponsor: Daiichi Sankyo Co., Ltd. | Trial completion date: Feb 2026 ➔ Mar 2027

Trial completion date • Giant Cell Tumor of Bone • Oncology • Tenosynovial Giant Cell Tumor

Surviving microglia and nonmicroglial progenitors contribute to microglial repopulation following colony-stimulating factor 1 receptor inhibition. (PubMed, Neuroreport) - "Microglial repopulation primarily involves proliferation of surviving microglia but can recruit nonmicroglial progenitors when depletion is exhaustive. These insights resolve prior inconsistencies and guide therapeutic strategies for microglial replacement treatment."

Journal • CNS Disorders • CX3CR1