galunisertib (LY2157299) / Eli Lilly - LARVOL DELTA

Galunisertib attenuates pulmonary fibrosis with silicosis in mouse via TGF-β/TRAF6/Beclin1 signaling pathway. (PubMed, Front Pharmacol) - "On the other hand, Galunisertib regulates autophagy and inhibits the activation, proliferation and migration of Silica-stimulated fibroblasts, alleviating fibrosis in silicosis mice. Altogether, Galunisertib may be a potential candidate drug for preventing pulmonary fibrosis."

Journal • Preclinical • Fibrosis • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • BECN1 • CASP3 • LAMP2 • TGFB1 • TRAF6

TGF-β facilitated mitochondria transfer in glioblastoma enhances tumor invasion and formate overflow (SNO 2025) - "For in vivo studies, orthotopic xenograft models were used to evaluate the impact of mitochondrial depletion, and immunohistochemistry was performed to quantify mitochondrial transfer. Here we show that TGF-β treatment of GB–astrocyte co-cultures significantly enhances mitochondria transfer rates and MT formation, which can be blocked by Galunisertib or SMAD inhibitors... This study identifies a regulatory role for TGF-β in glioblastoma–TME interactions, with SMAD signaling as a key pathway. Mitochondrial transfer from astrocytes supports GB proliferation, invasion, and survival.Reflection: Our findings offer new insights into communication of GB with its microenvironment, which may uncover novel treatment opportunities."

Brain Cancer • Glioblastoma • Oncology • Solid Tumor • TGFB1

TGF-β facilitated mitochondria transfer in glioblastoma enhances tumor invasion and formate overflow (SNO 2025) - "For in vivo studies, orthotopic xenograft models were used to evaluate the impact of mitochondrial depletion, and immunohistochemistry was performed to quantify mitochondrial transfer. Here we show that TGF-β treatment of GB–astrocyte co-cultures significantly enhances mitochondria transfer rates and MT formation, which can be blocked by Galunisertib or SMAD inhibitors... This study identifies a regulatory role for TGF-β in glioblastoma–TME interactions, with SMAD signaling as a key pathway. Mitochondrial transfer from astrocytes supports GB proliferation, invasion, and survival.Reflection: Our findings offer new insights into communication of GB with its microenvironment, which may uncover novel treatment opportunities."

Brain Cancer • Glioblastoma • Oncology • Solid Tumor • TGFB1

Targeting hepatocytic TβRI ameliorates liver metastatic outcomes by revitalizing stem-like CD8+ Tex subsets. (PubMed, Nat Commun) - "Furthermore, therapeutic delivery of Galunisertib using choline-modified lipid nanoparticles synergizes with αPD-1, fostering the conversion of exhausted CD8⁺ T cells into responsive Ly108⁺CX3CR1⁺ subsets and suppressing liver metastases. Collectively, our results identify hepatocyte TGFβ signaling as a targetable checkpoint against liver metastases."

IO biomarker • Journal • Oncology • CD4 • CD8 • CX3CR1 • LGALS9

Galunisertib attenuates pulmonary fibrosis with silicosis in mouse via TGF-β/TRAF6/Beclin1 signaling pathway (Frontiers) - "We found that Galunisertib has good anti-fibrosis activity both in vitro and in vivo. A 4-week Galunisertib treatment markedly ameliorated inflammation and fibrosis. Moreover, the results revealed that Galunisertib inhibited the expression of TGF-β, downregulated the major fibrotic protein expression of collagen I and a-smooth muscle actin (α-SMA), thereby switching the progression of fibroblast-to-myofibroblast transition (FMT)."

Preclinical • Fibrosis • Pulmonary Disease

TGF-β facilitated mitochondria transfer in glioblastoma enhances tumor invasion and formate overflow (WFNOS 2025) - "For in vivo studies, orthotopic xenograft models were used to evaluate the impact of mitochondrial depletion, and immunohistochemistry was performed to quantify mitochondrial transfer. Here we show that TGF-β treatment of GB–astrocyte co-cultures significantly enhances mitochondria transfer rates and MT formation, which can be blocked by Galunisertib or SMAD inhibitors... This study identifies a regulatory role for TGF-β in glioblastoma–TME interactions, with SMAD signaling as a key pathway. Mitochondrial transfer from astrocytes supports GB proliferation, invasion, and survival.Reflection: Our findings offer new insights into communication of GB with its microenvironment, which may uncover novel treatment opportunities."

Brain Cancer • CNS Tumor • Glioblastoma • TGFB1

TGF-β facilitated mitochondria transfer in glioblastoma enhances tumor invasion and formate overflow (WFNOS 2025) - "For in vivo studies, orthotopic xenograft models were used to evaluate the impact of mitochondrial depletion, and immunohistochemistry was performed to quantify mitochondrial transfer. Here we show that TGF-β treatment of GB–astrocyte co-cultures significantly enhances mitochondria transfer rates and MT formation, which can be blocked by Galunisertib or SMAD inhibitors... This study identifies a regulatory role for TGF-β in glioblastoma–TME interactions, with SMAD signaling as a key pathway. Mitochondrial transfer from astrocytes supports GB proliferation, invasion, and survival.Reflection: Our findings offer new insights into communication of GB with its microenvironment, which may uncover novel treatment opportunities."

Brain Cancer • Glioblastoma • Solid Tumor • TGFB1

The role of TGF-β1 in chronic multilobar segmental bronchial stenosis and advances in targeted drug research. (PubMed, Front Pharmacol) - "In recent years, groundbreaking progress has been made in research on therapeutics targeting the TGF-β1 signaling pathway, including monoclonal antibodies (e.g., Fresolimumab), small molecule kinase inhibitors (e.g., Galunisertib, TEW-7197), and novel targeted delivery systems. Furthermore, it proposes future research directions focused on CMBS-specific applications, such as validating these therapeutics in preclinical CMBS models, developing inhaled formulations for localized delivery, establishing biomarker-driven patient stratification, and exploring combination therapies with anti-fibrotic agents. This aims to provide a comprehensive theoretical foundation for elucidating the disease's pathology and developing novel, precise diagnostic and therapeutic strategies for CMBS."

Journal • Review • Asthma • Chronic Cough • Chronic Obstructive Pulmonary Disease • Cough • Immunology • Infectious Disease • Inflammation • Pulmonary Disease • Respiratory Diseases • Tuberculosis • TGFB1

Plasma Transforming Growth Factor-β1 (TGF-β1) Levels Increase with Age and Aortic Stenosis Progression and Low-Dose Galunisertib Attenuates Disease Progression in Mice (ASH 2023) - "1. Increases in plasma TGF-β1 levels may be a valuable surrogate marker of AS progression. 2."

Preclinical • Cardiovascular • Congestive Heart Failure • Coronary Artery Disease • Diabetes • Fibrosis • Heart Failure • Immunology • APOB • TGFB1 • TGFBR1

Platelet to Lymphocyte Ratio (PLR) As a Marker for Aortic Stenosis Development in a Mouse Model: Relationship to Platelet TGFβ1 (ASH 2024) - "2. Demonstration of higher PLR in mice with altered TGF-β1, via either platelet-specific TGF-β1 depletion or treatment with galunisertib, along with finding a lower NLR in the latter, warrants further study into the mechanism by which PLR may serve as a prognostic marker for AS progression apart from inflammation."

Preclinical • Cardiovascular • Congestive Heart Failure • Heart Failure • Inflammation • APOB • TGFB1

Feasibility IB trial of paclitaxel/carboplatin + Galunisertib. (a small molecule inhibitor of the kinase domain of type 1 TGF-B receptor) in patients with newly diagnosed, persistent or recurrent carcinosarcoma of the uterus or ovary. (PubMed, Gynecol Oncol) - P1 | "GB with CT was well-tolerated with 1 DLT noted. The study was prematurely stopped when the development of GB was discontinued, but targeting TGFb downstream signaling remains of interest."

Journal • Carcinosarcoma • Hematological Disorders • Neutropenia • Oncology • Sarcoma • Solid Tumor

CXCL1 Promotes Osteoblast Autophagy and Inhibits Ferroptosis Through the Activation of the TGF-β/Smad Signalling Pathway. (PubMed, J Cell Mol Med) - "Primary rat osteoblasts were treated with recombinant CXCL1, shRNA constructs and pathway modulators, such as Galunisertib, Fer-1 and Chloroquine (CQ). Our findings suggest that CXCL1 promotes osteoblast differentiation by inhibiting ferroptosis and enhancing autophagy through activation of the TGF-β/Smad signalling pathway. Collectively, our results highlight CXCL1 as a promising therapeutic target for osteoporosis."

Journal • Osteoporosis • Rheumatology • ACSL4 • BECN1 • CXCL1 • TGFB1

Targeted Therapies Modulating Mesenchymal-Epithelial Transition-Linked Oncogenic Signaling in the Tumor Microenvironment: Comparative Profiling of Capmatinib, Bemcentinib, and Galunisertib. (PubMed, J Clin Med) - "Although these targeted therapies show potential to overcome resistance and improve patient outcomes, challenges remain due to the complex regulation of EMP. Future directions focus on refining combination strategies and advancing personalized approaches to enhance efficacy across multiple cancer types."

Biomarker • Journal • Review • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • AXL • GAS6 • MET • TGFB1

The integration of single-cell and metabolomics reveals the increase of oxidative phosphorylation during the liver metastasis of colorectal cancer. (PubMed, Cancer Metab) - "This study identifies OXPHOS upregulation as a key metabolic alteration during CRC liver metastasis, which could be induced by TGFβ signaling pathway. These findings contribute to a refined understanding of CRC metabolic adaptation in liver metastases and may inform therapeutic strategies targeting OXPHOS in advanced CRC."

Journal • Colorectal Cancer • Oncology • Solid Tumor

Dynamics of Nectin-4 surface level expression on urothelial cancer cells identifies new co-treatment approaches with Enfortumab Vedotin (DGU 2025) - "Question: Urothelial carcinoma (UC) is heterogeneous presenting significant therapeutic challenges. Our findings confirm TGF-β-mediated subtype switching between luminal and basal/squamous. The clinically significant upregulation of N4 following TGF-β suggests benefit of combining Galunisertib with EV and Pembrolizumab to enhance efficacy and overcome resistance. Given the clinical success of TGF-β inhibitors in various cancer types, this combination warrants further investigation in clinical trials."

Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer • CD44 • NECTIN4 • TGFB1

TME-responsive nanoparticles co-targeting VCP, NETs, and dual immune checkpoints for immune revitalization in EGFR/PD-L1/CTLA-4-driven colorectal cancer. (PubMed, Biomed Pharmacother) - "The formulation co-delivered NMS-873 (NM), a VCP/p97 inhibitor, to induce endoplasmic reticulum stress (ERS) and proteostasis collapse, together with bispecific PD-L1/CTLA-4 aptamers (P1C4) for dual checkpoint blockade. A complementary SLN formulation encapsulating galunisertib (G) and DNase (DN) degraded neutrophil extracellular traps (NETs) and suppressed tumor-associated neutrophils (TANs), thereby reshaping the immunosuppressive TME...In vivo PET/MRI imaging and immunohistopathological analyses confirmed selective tumor accumulation and effective tumor regression. This peptide-guided, TME-tailored SLN strategy achieves coordinated immune reprogramming, ERS induction, EMT/CSC reversal, NET disruption, and dual checkpoint blockade, offering a clinically translatable platform to overcome chemoimmunotherapy resistance in EGFR/PD-L1/CTLA-4-driven CRC."

Journal • Colorectal Cancer • Oncology • Solid Tumor • CCL4 • CDH1 • CDH2 • CXCR2 • EGFR • IFNG • IL10 • IL12A • IL2 • IL4 • IL5 • IL9 • MMP9 • MYC • NANOG • PD-L1 • POU5F1 • SNAI2 • TGFB1 • TNFA

BCAR3 confers resistance to cisplatin in head and neck squamous cell carcinoma by sustaining TGF-β/SMAD signaling. (PubMed, Cell Signal) - "Moreover, inhibition of TGF-β/SMAD signaling through treatment with galunisertib achieved synergistic efficacy with cisplatin. The above findings demonstrate that BCAR3 is a positive regulator of TGF-β/SMAD signaling-mediated intrinsic cisplatin resistance. Targeting the BCAR3/TGF-β/SMAD axis might be a promising therapeutic strategy for overcoming cisplatin resistance in HNSCC."

Journal • Breast Cancer • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • BCAR3 • SMAD4 • TGFB1

Structure-based design of alicyclic fused pyrazole derivatives for targeting TGF-β receptor I kinase: molecular docking and dynamics insights. (PubMed, J Comput Aided Mol Des) - "TGF-β receptor I kinase plays a significant role in cancer biology and is a well-established target for cancer drug development, as evidenced by active molecules like Galunisertib (LY2157229)...Molecular Dynamics simulation study indicated that specific aminoacid residue interaction with TGF-β receptor I kinase. Additionally, DFT calculations were conducted on the active molecules to gain deeper insights into their electronic properties, supporting their potential as effective anticancer agents."

Journal • Oncology • TGFB1

The activity of EGFR CAR-NK and CAR-T cells against EGFR inhibitor-resistant NSCLC and drug-tolerant persister cells. (PubMed, Clin Cancer Res) - "EGFR-directed cellular therapies, particularly EGFR CAR-NK cells, demonstrate activity against EGFR-mutant DTPCs and DRCs in vitro and in vivo, with enhanced activity observed when combined with EGFR TKIs or TGF-β pathway blockade."

IO biomarker • Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • NKG2D • TGFB1

Unveiling therapeutic potential: In Silico discovery of prognostic markers and potential inhibitors for TGFßR1 in pancreatic cancer. (PubMed, Comput Biol Chem) - "These hits exhibited lower free energies (ΔG) as compared to the benchmark inhibitors, Galunisertib and Vactosertib. The results offer valuable insights into the binding mechanism of protein TGFßR1 and its role in the disease, suggesting that targeting the TGF-ß signaling pathway may represent a promising therapeutic strategy."

Biomarker • Journal • Oncology • Pancreatic Cancer • Solid Tumor • AHNAK2 • IGFBP3 • LAMC2 • SMAD4 • TSC2

Harnessing TGF-β signaling to improve testicular organoid development from dissociated testicular cells. (PubMed, Stem Cell Res Ther) - "This work presents a simple and efficient method for development of well-organized and functional TOs which can be investigated as a complementary treatment with any other TO culture systems."

Journal • Developmental Disorders • TGFB1

The effects of TGF-β receptor I inhibitors on myofibroblast differentiation and myotube formation. (PubMed, Front Cell Dev Biol) - "Galunisertib inhibited MyoD gene expression (at 20 µM), but not MyoG nor MyHC. Galunisertib may have potential for improving muscle wound healing following injury."

Journal • Immunology • ACTA2 • COL1A1 • Myogenin • TGFB1

Exploring the Mechanisms of the Ferroptosis-Related Gene TGFBR1 in Autoimmune Uveitis Based on Machine Learning Models. (PubMed, ACS Omega) - "Conversely, TGFBR1 inhibition via Galunisertib alleviated retinal inflammation and reversed ferroptosis- and immunity-related protein expression. These findings suggest that TGFBR1 contributes to AU pathogenesis by linking ferroptosis and immune imbalance and may serve as a potential biomarker and therapeutic target, particularly in BD-associated uveitis."

Journal • Immunology • Inflammation • Ocular Inflammation • Ophthalmology • Uveitis • FOXP3 • GPX4 • IL17A • TGFBR1 • ZFAS1

Effect of transforming growth factor beta receptor I inhibitors on myotube formation in vitro. (PubMed, Sci Rep) - "The aim of this study was to investigate the effect of five transforming growth factor-beta receptor I (TGFßRI) inhibitors on myotube formation in vitro; galunisertib, SM16, AZ12799734, SB431542 and IN1130. Only galunisertib had no effect on the fusion index. These results show that galunisertib does not impair the formation of myotubes from C2C12 myoblasts and might be suitable as an anti-fibrotic therapy for muscle regeneration."

Journal • Preclinical • Fibrosis • Immunology

Wnt-directed CXCL12-expressing apical papilla progenitor cells drive tooth root formation. (PubMed, Nat Commun) - "Canonical Wnt inactivation inhibits odontoblast fates of CXCL12+ AP cells and induces substantial root truncation, with their aberrant fibroblast fates suppressed by TGF-β receptor inhibitor galunisertib. Therefore, CXCL12+ AP cells maintain odonto-cementogenic fates in a Wnt-dependent manner, identifying these cells as pivotal dental mesenchymal progenitor cells driving tooth root formation with substantial plasticity."

Journal • CXCL12 • TGFB1