takinib (EDHS-206) / Duke University - LARVOL DELTA

TAK1 Impedes Peripheral Nerve Regeneration After Injury by Evoking Sustained Inflammation. (PubMed, Am J Pathol) - "The results show that TAK1 overexpression impairs nerve regeneration and functional recovery, whereas pharmacological inhibition of TAK1 with Takinib promotes these processes...This activation drives chemokine expression, leading to enhanced recruitment of M1 macrophages and the establishment of a proinflammatory microenvironment that impedes remyelination and nerve regeneration. Collectively, these findings identify TAK1 as a critical negative regulator of peripheral nerve repair and highlight TAK1 inhibition as a potential therapeutic approach for improving recovery following PNI."

Journal • Inflammation • TNS1

Novel imidazothiadiazole-based TAK1 inhibitors with anticancer and anti-inflammatory activity (ACS-Fall 2026) - "Our compounds demonstrate potent TAK1 inhibitory activity, surpassing known inhibitors such as Takinib and Tuspetinib, and effectively reduce pro-inflammatory cytokines including IL-6 and TNF-α. Furthermore, these inhibitors exhibit significant antitumor activity in ovarian cancer models, suppressing A2780 tumor growth both in vitro and in vivo. Future studies will focus on optimizing pharmacokinetic properties and further evaluating the clinical potential of these inhibitors."

Immunology • Oncology • Ovarian Cancer • Solid Tumor • IL6 • TNFA

Design and development of small molecule kinase inhibitors targeting TAK1 for inflammatory diseases | Poster Board #1190 (ACS-Fall 2026) - "The optimized compounds demonstrated strong TAK1 inhibition, outperforming the known inhibitor Takinib and Tuspetinib. In macrophage-based assays, the lead candidates effectively suppressed pro-inflammatory cytokines, including TNF-α and IL-6, with submicromolar IC50 values, showing markedly improved activity compared to the reference inhibitor HS-276. Following evaluation of pharmacokinetic properties and safety profiles, including cardiotoxicity assessment, these compounds are being advanced for in vivo validation in an arthritis mouse model. Overall, these findings highlight imidazothiadiazole-based TAK1 inhibitors as promising candidates for the development of new anti-inflammatory therapeutics"

Cardiovascular • Immunology • Inflammation • IL6 • TNFA

Design and development of small molecule kinase inhibitors targeting TAK1 for inflammatory diseases | Poster Board #1755 (ACS-Fall 2026) - "The optimized compounds demonstrated strong TAK1 inhibition, outperforming the known inhibitor Takinib and Tuspetinib. In macrophage-based assays, the lead candidates effectively suppressed pro-inflammatory cytokines, including TNF-α and IL-6, with submicromolar IC50 values, showing markedly improved activity compared to the reference inhibitor HS-276. Following evaluation of pharmacokinetic properties and safety profiles, including cardiotoxicity assessment, these compounds are being advanced for in vivo validation in an arthritis mouse model. Overall, these findings highlight imidazothiadiazole-based TAK1 inhibitors as promising candidates for the development of new anti-inflammatory therapeutics"

Cardiovascular • Immunology • Inflammation • IL6 • TNFA

AGGF1 delays endothelial cellular senescence through the TGFB3-TAK1-AMPK signaling axis. (PubMed, Biogerontology) - "Additionally, this proposed association was supported by pharmacological inhibition (Takinib, Compound C) and TGFB3 knockdown, which abrogated AGGF1-mediated protection. Collectively, we identified that AGGF1 is critical for regulating a proposed TGFB3-TAK1-AMPK regulatory module, which delays endothelial senescence partially through maintenance of mitochondrial morphology. Our study provides evidence that AGGF1 plays an important role in metabolic control and cellular senescence."

Journal • AGGF1 • IL6 • TGFB3

A novel combination for in vivo breast cancer treatment: TAK1 inhibition combined with metformin and Lentinula edodes compounds synergistically reinvigorates CD8+ T Cells. (PubMed, J Transl Med) - "This study suggests that the Tak-Met-LEME combination treatments may inhibit BC progression by increasing CD8+ CD28+ T cell population in tumor tissue and decreasing tumor progression."

IO biomarker • Journal • Preclinical • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CD8 • HAVCR2 • MUC1 • NR4A1

Blockade of Tumor TAK1 Induces DNA Damage and Immunogenic cGAS-STING Pathway Activation in Pancreatic Cancer. (PubMed, Gastroenterology) - "We uncover TAK1 as a critical mediator in maintaining genomic integrity and highlights its potential as a therapeutic target to induce an inflamed TME that sensitizes PDAC to ICB."

Journal • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CD4 • CD8 • CGAS • KRAS • MAP3K7 • RAD51 • STING • TGFB1

Targeting TAK1 kinase triggers anti-tumor immunity and sensitizes pancreatic cancer to checkpoint blockade (AACR 2025) - "The pharmacological inhibition of the TAK1 using selective TAK1 inhibitor Takinib significancy reduces tumor progression, prolong overall survival, enhances intratumoral CD4+ and CD8+ effector T cells, and decreases myeloid infiltration in the p48-Cre/TP53f/f/LSL-KRASG12D (KPC) mouse PDAC model...Mechanistically, inhibition of TAK1 in PDAC cells triggers cGAS-STING signaling by inducing cytosolic DNA damage which facilitates cytotoxic CD8+ T cell-dependent cell death. Together, our data provide the rationale for combining TAK1 inhibition with immune checkpoint blockade (anti-PD-1 and anti-CTLA4) as a therapeutic strategy for PDAC patients."

Checkpoint block • Checkpoint inhibition • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CD4 • CD8 • KRAS • MAP3K7 • TGFB1

Transfer Factor Alleviates Bovine Mastitis and Protects Mammary Epithelial Barrier via the TAK1/NF-κB/MLCK Signaling Axis. (PubMed, J Anim Sci) - "It also mitigated LPS-induced changes via inhibiting the nuclear factor κB (NF-κB) pathway, similar to NF-κB inhibitor Bay 11-7082, and blocked NF-κB activation by inhibiting the transforming growth factor-β-activated kinase 1 (TAK1) pathway, comparable to TAK1 inhibitor Takinib. Our findings demonstrate that TF, by concurrently eliciting anti-inflammatory and barrier-repair effects via inhibition of the TAK1/NF-κB/MLCK axis, effectively alleviates bovine mastitis. This study furnishes a robust molecular framework for deploying TF as a non-antibiotic tool in the sustainable control of mastitis."

Journal • IL1B • IL6 • MYLK • NECTIN4 • OCLN • TJP1

Immune cell-derived cytokines synergistically interact to drive synovial fibroblast invasive function and metabolic capacity. (PubMed, J Autoimmun) - "Importantly, in RA ex vivo synovial explants (reflecting the inflamed joint), Takinib reduced spontaneous release of pro-inflammatory mediators and the process of synovial growth. In conclusion, IL-1β/TGF-β synergistically drive a pathogenic RA-FLS phenotype in RA, blockade of which reduces inflammatory and invasive mechanisms."

Journal • Immunology • Inflammation • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • CXCL5 • CXCL8 • IL1B • MMP3 • PFKFB3 • PKM • SLC2A1 • TGFB1

Targeting tumor-intrinsic TAK1 triggers anti-tumor immunity and sensitizes pancreatic cancer to checkpoint blockade. (PubMed, bioRxiv) - "Pharmacological inhibition of TAK1 with Takinib, or genetic deletion of MAP3K7 in autochthonous p48-Cre;TP53 flox/flox ;LSL-KRAS G12D GEMM, enhances intratumoral CD4 + and CD8 + effector T cell infiltration and renders immune checkpoint blockade (ICB) effective...At the molecular level, TAK1 phosphorylates Ephrin Receptor A2 (EphA2) at Serine 897, which in turn phosphorylates RAD51 at Tyrosine 315, a key DNA repair protein involved in homologous recombination. We uncover TAK1 as a critical mediator in maintaining genomic integrity and highlights its potential as a therapeutic target to induce an inflamed TME that sensitizes PDAC to ICB."

Checkpoint inhibition • Journal • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CD4 • CD8 • CGAS • KRAS • MAP3K7 • RAD51 • STING • TGFB1 • TP53

TAK1 blockade induces DNA damage and immunogenic cGAS–STING pathway activation in pancreatic cancer (SITC 2025) - "Pharmacological inhibition of TAK1 with Takinib, or genetic deletion of MAP3K7 in autochthonous p48-Cre; TP53flox/flox; LSL-KRASG12D GEMM, enhances intratumoral CD4+ and CD8+ effector T cell infiltration and renders immune checkpoint blockade (ICB) effective. Mechanistically, TAK1 inhibition induces DNA damage and cytoplasmic DNA leakage, which activates the cyclic GMP-AMP synthase-Stimulator of Interferon Genes (cGAS-STING) DNA sensing pathway, triggering inflammatory responses that promote adaptive immune cell infiltration. At the molecular level, TAK1 phosphorylates Ephrin Receptor A2 (EphA2) at Serine 897, which in turn phosphorylates RAD51 at Tyrosine 315, a key DNA repair protein involved in homologous recombination.Conclusions We uncover TAK1 as a critical mediator in maintaining genomic integrity and highlights its potential as a therapeutic target to induce an inflamed TME that sensitizes PDAC to ICB."

Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CD4 • CD8 • CGAS • KRAS • MAP3K7 • RAD51 • STING • TGFB1

TAK1 blockade induces DNA damage and immunogenic cGAS–STING pathway activation in pancreatic cancer (AACR-NCI-EORTC 2025) - "Pharmacological inhibition of TAK1 with Takinib, or genetic deletion of MAP3K7 in autochthonous p48-Cre; TP53flox/flox; LSL-KRASG12D GEMM, enhances intratumoral CD4+ and CD8+ effector T cell infiltration and renders immune checkpoint blockade (ICB) effective. We uncover TAK1 as a critical mediator in maintaining genomic integrity and highlights its potential as a therapeutic target to induce an inflamed TME that sensitizes PDAC to ICB."

Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CD4 • CD8 • CGAS • KRAS • MAP3K7 • RAD51 • STING • TGFB1

A Dual Inhibitor of TAK1 and MAP4K2, NG25, Suppresses Cytokine-driven Inflammation in Juvenile Idiopathic Arthritis Synovial Fibroblasts (ACR Convergence 2025) - "The efficacy of NG25 was further compared with different TAK1 inhibitors (5Z-7-oxozeaenol (5Z), takinib, or HS-276). Our preliminary findings delineate NG25's potential anti-inflammatory and anti-chemotactic activities in JIASFs. These findings lay a foundation for testing the efficacy of NG25 in animal models of JIA."

Idiopathic Arthritis • Immunology • Inflammation • Rheumatology • CDH11 • CXCL5 • CXCL8 • ICAM1 • IFNG • IL1B • IL6 • LY6G6D • MMP3 • PDPN • PTGS2 • TNFA • VCAM1

TAK1 blockade induces DNA damage and immunogenic cGAS–STING pathway activation in pancreatic cancer Free (AACRPanCa 2025) - "Inhibiting TAK1 pharmacologically (with Takinib) or genetically in autochthonous PDAC mice enhances T cell infiltration, reduces immunosuppressive macrophages, and sensitizes tumors to immune checkpoint blockade (ICB)...Mechanistically, we found that TAK1 phosphorylates EphA2 (Ser897), which in turn phosphorylates RAD51 (Tyr315), a critical driver of homologous recombination repair. Our findings reveal a novel role for TAK1 in maintaining genomic integrity and underscore its therapeutic potential in reprogramming the TME to sensitize PDAC to ICB."

Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • HRD • MAP3K7 • RAD51 • TGFB1

Emodin Alleviates Monocrotaline-Induced Pulmonary Arterial Hypertension by Directly Targeting TAK1. (PubMed, Drug Des Devel Ther) - "The indispensable role of TAK1 in mediating emodin's effects was corroborated through pharmacological blockade with Takinib, a highly potent and selective TAK1 inhibitor. The experiment has demonstrated for the first time that emodin directly targets TAK1, downregulates the expression of IL-17A, IL-17RA, and Phospho-TAK1, blocks the activation of the IL-17 signaling pathway, inhibits PASMCs proliferation, and alleviates PAH. This study provides a theoretical basis for the clinical application of emodin."

Journal • Cardiovascular • Hypertension • Pneumonia • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • IL17A • IL17RA • MAP2K3

Takinib exhibits antitumor effects in NF1-associated plexiform neurofibroma via NF-κB pathway inhibition (ESDR 2025) - "Selumetinib, a MEK inhibitor, has been approved for treating plexiform neurofibromas (PN) in patients with neurofibromatosis type 1 (NF1), but some clinical cases of resistance have been reported. To explore the molecular mechanism of this variability, we conducted RNA sequencing to compare gene expression profiles between Takinib-sensitive and -resistant cell lines and identified candidate genes potentially involved in Takinib-induced antitumor effects. These findings suggest that the NF-κB pathway contributes to PN cell proliferation and highlight the need for further research into alternative therapeutic strategies targeting this pathway."

Genetic Disorders • Neurofibromatosis • Oncology • Solid Tumor • NF1

Investigating The Effect of Two TAK1 Inhibitors on an Ovarian Granulosa Cell Tumor-Derived Cell Line (ENDO 2025) - "Transcriptomic analysis suggests that takinib exhibits greater specificity for TAK1. These findings underscore the potential of TAK1 inhibition as a therapeutic approach for aGCT."

Preclinical • Oncology • Ovarian Cancer • Solid Tumor • CASP3 • CASP7 • FOXL2 • XIAP

EXPRESS: TLR3 mediates central sensitization in a chronic migraine model induced by repeated nitroglycerin through the ERK signaling pathway. (PubMed, Mol Pain) - "In addition, we investigated the effects of TLR3 inhibitor(CU CPT4a), MEK inhibitor(PD98059), TRAF6 inhibitor(C25-140), and TAK1 inhibitor (Takinib) on chronic migraine-like behavior, and activation of the ERK pathway in the Trigeminal nucleus caudalis(TNC). Concurrent inhibition of TLR3 function, TRAF6, TAK1, and the ERK pathway counteracted these changes and alleviated hyperalgesia in CM mice. Con-clusions: Our findings suggest that TLR3 may play a role in central sensitization in CM mice by TRAF6-TAK1 axis modulating the ERK signaling pathway."

IO biomarker • Journal • CNS Disorders • Migraine • Neuralgia • Pain • FOS • TLR3 • TRAF6

Senescent retinal pigment epithelial cells promote angiogenesis in choroidal neovascularization via the TAK1/p38 MAPK pathway. (PubMed, Exp Eye Res) - "Consistently, we found that the TAK1 inhibitors 5Z-7-oxozeaenol and takinib reversed the effects of conditioned media from senescent ARPE-19 cells on the wound healing, migration, survival, and tube formation abilities of HUVECs...Thus, senescent RPE cells may promote angiogenesis via the TAK1/p38 MAPK pathway. Further, inhibiting TAK1 expression alleviates pathological neovascularization and improves retinal function in a laser-induced CNV rat model, highlighting the therapeutic potential of this approach for treating nAMD."

Journal • Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

Dexamethasone's Clinical Efficacy in Experimental Autoimmune Pancreatitis Correlates with a Unique Transcriptomic Signature, Whilst Kinase Inhibitors Are Not Effective. (PubMed, Biomedicines) - "(4) Dexamethasone effectively reduced AIP severity, while takinib and tofacitinib were ineffective. The unique gene expression profile in dexamethasone-treated mice may provide a basis for identifying new drug targets for AIP treatment."

Journal • Fibrosis • Immunology • Inflammation • Pancreatitis • CD69 • CD8 • FOXP3 • IL2RA

Impact of Combination Therapy with Chemical Drugs and Megavoltage X-ray Exposure on Breast Cancer Stem Cells' Viability and Proliferation of MCF-7 and MDA-MB-231 Cell Lines. (PubMed, Curr Pharm Des) - "Anti-cancer and cytotoxic effects of metformin can be effective in this strategy. In conclusion, the combination of conventional chemotherapeutic drugs, including SB203580, metformin, and takinib with X-ray exposure can be a new approach to diminish the drug resistance of breast cancer."

Cancer stem • Combination therapy • Journal • Preclinical • Breast Cancer • Oncology • Solid Tumor • CXCR4

Neuroprotective effects of takinib on an experimental traumatic brain injury rat model via inhibition of transforming growth factor beta-activated kinase 1. (PubMed, Heliyon) - "As a result, an enhancement of neuronal function and survival was observed post-TBI. These findings highlight the medicinal value of Takinib in the management of TBI and offer an experimental justification for further investigation of TAK1 as a potential pharmacological target."

Journal • Preclinical • CNS Disorders • Inflammation • Oncology • Vascular Neurology • CASP3 • CLDN5 • IL1B • TJP1 • TNFA

Discovery of imidazo[1,2-b]pyridazine-containing TAK1 kinase inhibitors with excellent activities against multiple myeloma. (PubMed, RSC Med Chem) - "Under similar conditions, the known TAK1 inhibitor, takinib, inhibits the kinase with an IC of 187 nM. Compound 26 and analogs thereof inhibit the growth of multiple myeloma cell lines MPC-11 and H929 with GI values as low as 30 nM. These compounds have the potential to be translated into anti-MM therapeutics."

Journal • Hematological Malignancies • Multiple Myeloma • Oncology

Upregulation of TRIM16 mitigates doxorubicin-induced cardiotoxicity by modulating TAK1 and YAP/Nrf2 pathways in mice. (PubMed, Biochem Pharmacol) - "The clinic application of doxorubicin (DOX) is severely limited by its severe cardiotoxicity. This effect was nullified by siTRIM16 or TAK1 inhibitor Takinib. Collectively, the current study elaborates that upregulating TRIM16 mitigates DOX-induced cardiotoxicity through anti-inflammation and anti-oxidative stress by modulating TAK1-mediated p38 and JNK as well as YAP/Nrf2 pathways, and targeting TRIM16 may provide a novel strategy to treat DOX-induced cardiotoxicity."

Journal • Preclinical • Cardiovascular • Fibrosis • Immunology • Inflammation • Targeted Protein Degradation • NFE2L2 • TRIM16 • YAP1