galunisertib (LY2157299) / Eli Lilly - LARVOL DELTA

Transforming growth factor (TGF)-β isoform-specific signalling and inhibition in dermal and lung fibroblasts in systemic sclerosis (ERS 2026) - "TGF-β2 and TGF-β3 have a more pronounced profibrotic effect than TGF-β1 on lung and dermal fibroblasts due to greater SMAD7 inhibition, and galunisertib has the potential to inhibit profibrotic fibroblast functions in SSc-ILD."

Fibrosis • Immunology • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases • Scleroderma • Systemic Sclerosis • IL6 • SMAD7 • TGFB1

Migrasome-propagated ITGβ3-TGFβ1 circuit orchestrates breast cancer brain metastasis by reprogramming the microglial niche. (PubMed, Cancer Biol Med) - "This study identified a targetable circuit in BCBM wherein tumor-derived migrasomes, via ITGβ3, engage microglia in a TGFβ1-centered crosstalk. Because this self-reinforcing ITGβ3-TGFβ1 axis sustains the pro-metastatic niche, its disruption might provide a rational therapeutic strategy."

Journal • Breast Cancer • Oncology • Solid Tumor • EGR1 • SMAD2 • TGFB1

Mesenchymal drift in ciliopathy iPSC-derived RPE reveals a convergent pathogenic cell state. (PubMed, Cell Rep) - "Despite heterogeneity in disease severity, consistent with underlying ciliary structural defects, all ciliopathy iRPE exhibit abnormal epithelial polarization and impaired mitochondrial health initiated by dysregulated TGF-β signaling-driven mesenchymal drift. Addressing these gene-agnostic disease phenotypes, our study identifies two drugs, pioglitazone, a mitochondrial metabolic modulator, and galunisertib, a TGFBR1 inhibitor, as potential therapeutic candidates for multiple ciliopathy subtypes."

Journal • Inherited Retinal Dystrophy • Ophthalmology • CEP290 • PRPF31 • TGFB1 • TGFBR1

Codelivery of nivolumab and Galunisertib by EGFR-targeted spherical polymeric nanoparticles for effective treatment of non-small cell lung cancer. (PubMed, Int J Pharm) - "In the concept of in vivo studies, biodistribution studies revealed that antibody-conjugated nanoparticles exhibited higher tumor accumulation compared to the control group. The targeted co-loaded nanoparticles maintained antitumor activity comparable to the free-drug combination while enabling tumor-directed delivery and showing a more favorable preliminary tolerability profile."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • TGFB1

Tumor-associated neutrophils in lung adenocarcinoma: from mechanisms to therapeutic targeting. (PubMed, Front Immunol) - "Furthermore, we evaluate current therapeutic strategies targeting TANs, such as CXCR1/2 inhibitors (SX-682, Navarixin), PAD4 inhibitors (Cl-amidine), NET-degrading enzymes (DNase I), TGF-β inhibitors (Galunisertib), and myeloid modulators, with a focus on LUAD-specific preclinical and clinical evidence. Major challenges, including off-target toxicity, infection risk, and the lack of predictive biomarkers, are discussed. By bridging mechanistic insights with translational opportunities, this review provides a framework for developing neutrophil-targeted combination therapies to overcome immunotherapy resistance in LUAD."

IO biomarker • Journal • Review • Infectious Disease • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CXCR1 • CXCR2 • IFNG • TGFB1

TGF-β Is Critical for Ovarian Cancer Migration, Invasion, and Chemosensitivity. (PubMed, Cancers (Basel)) - " TGF-β pathway inhibition successfully targeted many of the cancer cell behaviors that could contribute to suboptimally debulked patients and showed an additive anti-tumor effect in conjunction with cisplatin. LY2157299 treatment is clinically limited due to solubility, but other TGF-β inhibitors could be highly efficacious treatment options."

Journal • Oncology • Ovarian Cancer • Solid Tumor • TGFB1 • TGFBR1 • TGFBR2

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

Inhibition of TGF-β1/Smad signaling reverses the dedifferentiated phenotype of thyroid cancer cells in three-dimensional culture. (PubMed, J Endocrinol Invest) - "Galunisertib, a TGF-β type I receptor kinase inhibitor, effectively blocked TGF-β1 signaling in spheroids, suppressed cancer stem cell marker expression, and enhanced radioiodine uptake through upregulation of thyroid functional proteins, establishing TGF-β1 as a therapeutic target in thyroid cancer. Collectively, the established 3D culture model serves as a robust platform for investigating dedifferentiation in thyroid cancer and provides a basis for developing novel therapies against radioiodine resistance.Plain Language."

Journal • Oncology • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Papillary Carcinoma • TGFB1

Galunisertib Combined With Capecitabine in Advanced CRC With PM (clinicaltrials.gov) - P1/2 | N=31 | Active, not recruiting | Sponsor: The Netherlands Cancer Institute | Recruiting ➔ Active, not recruiting | Trial completion date: Apr 2025 ➔ Dec 2026 | Trial primary completion date: Apr 2025 ➔ Dec 2026

Enrollment closed • Trial completion date • Trial primary completion date • Colorectal Cancer • Oncology • Peritoneal Cancer • Solid Tumor

TGFβ signaling in inguinal hernias: from mouse to human (ENDO 2026) - "Next, primary LAM fibroblasts from Aromhum mice were treated with E2 with or without ESR1 antagonist (fulvestrant) to determine whether E2/ESR1 regulates expression of TGFβ ligands and receptors by qPCR. Additionally, Aromhum mice were treated with a TGFBR1 inhibitor, Galunisertib (50mg/kg, 3 times per week, intraperitoneal injection) to assess the in vivo role of TGFβ signaling in hernia development and LAM fibrosis/atrophy... TGFβ signal transduction is significantly elevated in Aromhum LAM and contributes to hernia development and possibly LAM fibrosis/atrophy. Preliminary data from snRNA-seq of human inguinal hernia patient LAM tissues demonstrate TGFβ pathway dysregulation, presenting a potential avenue for pharmacological therapeutic intervention."

Late-breaking abstract • Preclinical • Fibrosis • Gastroenterology • Immunology • ER • ITGB3 • LTBP1 • TGFB2 • TGFBR1 • TGFBR2 • THBS2

Effect of ESWT on the microcirculation of the lower extremity in rats with diabetic vasculopathy: An experimental animal study. (PubMed, Turk J Phys Med Rehabil) - "Forty healthy adult male Sprague-Dawley rats (mean weight: 226 ± 21 g; range, 205 to 247 g) were randomly assigned to five groups (n=8 per group): Control group (Group A), DV group (Group B), DV + ESWT group (Group C), DV + LY2157299 group (Group D), and DV + ESWT + LY2157299 group (Group E)...The expression of CD31 in the gastrocnemius, FAD, and blood flow was significantly higher in Groups C, D, and E than in Group B (p < 0.05), with the highest expression in Group E compared with Groups C and D (p < 0.05). Extracorporeal shock wave therapy can downregulate TGF-β1 expression, inhibit the PI3K/AKT pathway, increase gastrocnemius CD31 expression and lower limb blood flow, and improve blood microcirculation of lower limb skeletal muscle."

Journal • Preclinical • CD31 • PECAM1 • TGFB1

Experimental Study of YaJieShaBa Antialcoholic Hepatic Fibrosis Through TGF-β1/Smad Signaling Pathway. (PubMed, Mediators Inflamm) - "YJSB effectively inhibits the inflammatory and oxidative stress-related cascade by regulating the TGF-β1/Smad signaling pathway (TSSP), thus suppressing the progression of alcoholic HF. This demonstrates that YJSB possesses potential for combating alcoholic HF in animal models, providing experimental evidence for its subsequent research and clinical application."

Journal • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • CAT • CXCL8 • IL1B • IL6 • MYD88 • SMAD2 • SMAD3 • SMAD4 • TGFB1 • TLR4 • TNFA

Targeting the Spata13-TGFβRI interaction inhibits infection-driven capsular contracture via suppression of fibroblast activation. (PubMed, Acta Biochim Biophys Sin (Shanghai)) - "The TGFβRI inhibitor LY2157299 attenuates fibrosis in vivo. Strikingly, PT637 disrupts the Spata13-TGFβRI interaction and reduces both fibrosis markers and capsular thickness in biofilm-challenged rats. We define Spata13 as a novel regulator of infection-associated fibrosis and demonstrate that targeted disruption of Spata13-TGFβRI binding by PT637 offers a precision therapeutic strategy for capsular contracture."

Journal • Breast Cancer • Fibrosis • Immunology • Infectious Disease • Oncology • Solid Tumor • TGFB1

Chemoimmunotherapeutic sealants for postsurgical adjuvant therapy of malignant tumors. (PubMed, J Control Release) - "Herein, we report a chemoimmunotherapeutic fibrin sealant (CI-sealant) as a new postsurgical adjuvant therapy that converts the surgical cavity into an in situ "drug-immune depot" with localized release of immunogenic docetaxel/volasertib dual-drug nanocombo (iNCombo) and galunisertib, a TGF-β inhibitor that relieves immune suppression. Post-surgery adjuvant therapy with CI-sealant significantly prevents tumor recurrence in both murine 4 T1-Luc breast tumor and B16F10 melanoma models. This chemoimmunotherapeutic sealant opens a promising strategy for postsurgical adjuvant therapy of malignant tumors."

Journal • Breast Cancer • Melanoma • Oncology • Solid Tumor • Triple Negative Breast Cancer • TGFB1

A phase II combination study of galunisertib and capecitabine in patients with chemotherapy-resistant colorectal cancer with peritoneal metastases. (ASCO 2026) - P1/2 | "CRC of the mesenchymal subtype exhibits prominent TGF-β activation, contributing to drug resistance, including to 5-fluorouracil (5-FU)-based chemotherapy. The combination of galunisertib and capecitabine did not result in objective responses or long term stable disease in chemotherapy-resistant CRC patients with peritoneal metastases. The treatment was well tolerated and PK results for both compounds were similar to those described in the literature."

Clinical • P2 data • Colorectal Cancer • Oncology • Renal Disease • Solid Tumor • TGFB1

Can TGF-β inhibition (galunisertib) enhance response to enzalutamide in metastatic castration-resistant prostate cancer (mCRPC)?: Results from a randomized phase II trial. (ASCO 2026) - P2 | "The addition of galunisertib to enzalutamide did not improve the rPFS, OS, or PSA response compared to enzalutamide alone in patients with chemotherapy-naïve mCRPC with disease progression on abiraterone. These findings do not support further development of galunisertib plus enzalutamide in patients with mCRPC. Baseline characteristics of randomized patients."

Clinical • Metastases • P2 data • Anorexia • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • AR • TGFB1

Hepatic TGFβ1 signaling impairs insulin sensitivity via inducing insulin receptor substrate 1 degradation. (PubMed, Metabolism) - "These findings identify TGFβ1 as a key driver of hepatic insulin resistance by promoting CUL7-dependent IRS1 degradation, establishing a mechanistic link between obesity-associated cytokine signaling and impaired insulin action and highlighting the TGFβ1-CUL7-IRS1 axis as a potential therapeutic target for T2D."

Journal • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Targeted Protein Degradation • Type 2 Diabetes Mellitus • CUL7 • IRS1

TGF-beta inhibitors influence leishmania infection outcome in a susceptible host. (PubMed, Cytokine) - "BALB/c-derived peritoneal macrophages were infected with L. donovani promastigotes and treated with salirasib- a Ras inhibitor, angoline- an IL-6 inhibitor, SIS3- a SMAD3 inhibitor, or galunisertib- a TGF-β receptor inhibitor. Combined galunisertib and SIS3 treatment synergistically increased both pro-inflammatory and anti-inflammatory cytokines, notably IL-10, which may offset parasite clearance. These findings establish TGF-β receptor inhibition as a promising host-directed therapeutic approach against visceral leishmaniasis, while highlighting the immunoregulatory complexities of targeting TGF-β signaling."

Journal • Infectious Disease • IFNG • IL10 • IL12A • IL17A • SMAD3 • TGFB1 • TNFA

Therapeutic microneedles for myocardial repair. (PubMed, Trends Biotechnol) - "Recent studies have demonstrated tangible benefits: galunisertib-loaded MNs reduced fibrosis from ~14% to ~7%, and vascular endothelial growth factor (VEGF)-based MNs increased vascular density from ~0.2 to ~0.5 vessels per field. Mechanically adaptive and biodegradable MN platforms maintain stable contact with the beating heart and support programmable release profiles. This review synthesizes the current preclinical landscape of cardiac MN technologies and outlines the engineering and translational considerations that will guide their advancement toward future clinical applications."

Journal • Review • Cardiovascular • Fibrosis • Immunology • Myocardial Infarction

Investigating the interplay of transcription factor, ERG, and TGF-beta signaling in cervical cancer cells (AACR 2026) - "To further investigate the effects of ERG on TGF-β, galunisertib, a known inhibitor of TGF-β signaling, was used...ChIP-seq is being done to investigate the possible interactions between TGFB signaling and ERG occupancy on the genome in cervical cancer, which will be compared to ERG sites in extensively studied cancers. Together, these findings suggest that ERG promotes cervical cancer cell migration and invasion, at least in part by regulating TGF-β signaling."

Cervical Cancer • Oncology • Solid Tumor • ERG • SMAD2 • TGFB1

Crosstalk between ceramide and prostaglandin signaling mediates resistance to immune checkpoint blockade (AACR 2026) - "Targeting PGE2 production with celecoxib, but not aspirin, further enhanced responses when combined with LY2157299 and αPD-1 therapy. Finally, mIF analysis of nivolumab-treated pre-surgical human HNSCC specimens (responders vs. non-responders) corroborated these findings by demonstrating reduced tumor ceramide abundance, elevated PanCK+COX-2+ceramidelo populations, and decreased intratumoral CD8+ T cell density amongst non-responders. Collectively, these studies (1) establish a relevant model of ICB resistance, (2) define a mechanistic framework linking ceramide metabolism to prostaglandin-mediated immune suppression, and (3) highlight therapeutic strategies to target ICB resistance and improve patient outcomes."

Checkpoint block • Checkpoint inhibition • IO biomarker • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • CAPRIN1 • CD8 • CERS4 • PACERR • PTGS2 • TGFB1

Extracellular vesicle-mediated co-delivery of FSL-1 and LY2157299 for immunotherapy of small-cell lung cancer liver metastases (AACR 2026) - "In vivo, EVs efficiently targeted intrahepatic tumor sites, decreased liver tumor growth, and prolonged mouse survival. These data support EV‑mediated co‑delivery of FSL‑1 and LY2157299 as a macrophage‑centric strategy for SCLC liver metastasis."

Hepatocellular Cancer • Liver Cancer • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • TLR2

Targeting HCC tumor microenvironment interactions using an advanced HCC patient-derived on-chip model (AACR 2026) - "The screen revealed that SoC drugs sorafenib and lenvatinib reduced culture viability and induced profound changes in vascular bed organization, while atorvastatin decreased viability without affecting vascular structures...Tocilizumab, galunisertib, and vactosertib lowered IL6 levels, whereas halofuginone increased IL6. These findings highlight the utility of the PDChip model in visualizing drug-induced responses at both molecular and morphological levels, providing detailed insights into drug effects on specific cellular compartments within the HCC TME. This platform enabled a detailed evaluation of drug-induced responses in the tumor and associated microenvironment, highlighting their importance in preclinical research for understanding diseases and developing new drugs."

Biomarker • Clinical • Metastases • Tumor microenvironment • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor • IL6

Disrupting the TGF-β-regulated epithelial-mesenchymal transition, apoptotic and autophagic phenotypes of 3D glioblastoma spheroids via glycolytic inhibition. (PubMed, Explor Target Antitumor Ther) - "2-Deoxy-D-glucose (2DG), a glycolytic inhibitor, depleted ATP dose-dependently (30-300 μM) and prevented those increases both at the protein and transcriptional levels. This was also observed in 3D spheroids upon TGF-β transient siRNA-mediated silencing or when TGF-βR1 kinase activity was inhibited by galunisertib...3D spheroids require ATP and a TGF-β/TGF-βR1 autocrine signaling axis to recapitulate the apoptosis/autophagy phenotypes. Combining glycolysis inhibition with TGF-β signaling inhibition could offer a promising therapeutic strategy for this rare and lethal brain cancer."

IO biomarker • Journal • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • ATG16L1 • ATG7 • BCL2 • CASP7 • FASLG • PIK3C3 • TGFB1

ExIST Study of LY2157299 (Galunisertib) in Rectal Cancer (clinicaltrials.gov) - P2 | N=50 | Active, not recruiting | Sponsor: Providence Health & Services | Trial completion date: Dec 2025 ➔ Dec 2026

Trial completion date • Colorectal Adenocarcinoma • Colorectal Cancer • Oncology • Rectal Adenocarcinoma • Rectal Cancer • Solid Tumor • CRP