EC359 / Evestra - LARVOL DELTA

Fibroblast-Derived LIF Suppresses Osteogenesis Through LIFR/ STAT3 Signalling in Fracture Nonunion. (PubMed, Curr Med Chem) - "Together, these results nominate fibroblast-associated LIF as a niche-related inhibitory signal in nonunion, with effects that are most compatible with canonical LIFR/IL6ST-mediated STAT3 signalling."

Journal • Hematological Malignancies • Leukemia • Musculoskeletal Diseases • Oncology • Orthopedics • ALPL • IL6ST • LIF • LIFR

Small-molecule LIFR inhibitors attenuate renal tubulointerstitial fibrosis. (PubMed, Biochim Biophys Acta Mol Basis Dis) - "While novel LIFR small-molecule inhibitors EC330 and EC359 have shown therapeutic efficacy in cancer, their potential in treating kidney diseases remains unexplored...In vivo, EC330 attenuated ERK and STAT3 phosphorylation in fibroblasts and TECs, significantly mitigating both developing TIF in the unilateral ischemia-reperfusion injury model and established TIF in the aristolochic acid model. Collectively, our findings demonstrate that LIFR inhibition is a viable anti-fibrotic strategy and identify EC330 as a promising drug candidate for treating CKD."

Journal • Cardiovascular • Chronic Kidney Disease • Fibrosis • Hematological Malignancies • Immunology • Leukemia • Nephrology • Oncology • Renal Disease • Reperfusion Injury • LIF • LIFR • SMAD3 • TGFB1

Targeting LIF/LIFR signaling with EC359 overcomes chemoresistance and enhances chemotherapy efficacy in ovarian cancer (AACR 2026) - "In this study, we tested the hypothesis that the progression of OCa to therapy resistance is dependent on LIF/LIFR signaling and that the standard of care interventions will be enhanced by the disruption of LIF/LIFR signaling with the small molecule inhibitor EC359. The effectiveness of the LIFR inhibitor EC359, in combination with paclitaxel and/or carboplatin, was evaluated in both established and chemotherapy-resistant OCa cell lines, as well as in patient-derived xenograft (PDX) models. These findings provide compelling preclinical evidence that LIFR inhibition with EC359 is a promising strategy to enhance chemotherapy efficacy in OCa. Supported by NIH R01 CA266970."

Clinical • Gynecologic Cancers • Hematological Malignancies • Leukemia • Oncology • Ovarian Cancer • Solid Tumor • LIF • LIFR

ROCK2-regulated LIF-STAT3 drives immunosuppression in pancreatic cancer (AACR 2026) - "These findings demonstrate that tumor cell-intrinsic ROCK2 regulates LIF-STAT3, which mediates immunosuppression and can serve as a potential therapeutic target for PDAC."

IO biomarker • Hematological Malignancies • Leukemia • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • KRAS • LIF • LIFR • PD-L1 • STAT3 • TP53

LIFR inhibition with EC359 triggers ferroptosis to overcome chemoresistance in endometrial cancer (AACR 2026) - "For preclinical validation, patient-derived organoids (PDO) and xenograft (PDX) models of ECa were employed to determine the therapeutic efficacy of EC359 in combination in vivo. RNA-seq analysis of taxol-resistant ECa cells revealed upregulation of pathways associated with cell proliferation, stemness, and LIFR signaling, along with downregulation of apoptotic pathways. Our studies suggest that EC359 induces ferroptosis by disrupting antioxidant defenses and synergizes with chemotherapy and that EC359 serve as a promising strategy to overcome chemoresistance in advanced ECa."

Endometrial Cancer • Gynecologic Cancers • Hematological Malignancies • Leukemia • Oncology • Solid Tumor • LIF • LIFR

EC359, A new therapeutic drug for the treatment of low grade serous ovarian cancer (AACR 2024) - "EC359 enhanced the efficacy of trametinib, a currently used medication of LGSOC. Together, our findings support the existence of LIF/LIFR autocrine loops, and EC359 is a viable treatment option for LGSOC."

Gynecologic Cancers • Hematological Malignancies • Leukemia • Low Grade Serous Carcinoma • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Solid Tumor • BRAF • KRAS • LIF • LIFR • STAT3

Low-grade serous ovarian cancer is effectively treated with a combination of trametinib and LIFR inhibitor therapeutics (AACR 2025) - "These results indicate that the EC359 + trametinib combination therapy may provide a promising therapeutic approach for the treatment of LGSOC by enhancing the efficacy of trametinib and targeting critical signaling pathways."

Gynecologic Cancers • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Solid Tumor • BRAF • KRAS • LIFR • STAT3

Pharmacological inhibition of the LIF-LIFR autocrine loop reveals vulnerability of ovarian cancer to ferroptosis (AACR 2024) - "Collectively, our findings indicate that the LIF/LIFR autocrine loop plays an essential role in OCa progression and that EC359 could be a promising therapeutic agent for OCa."

Epithelial Ovarian Cancer • Gynecologic Cancers • Hematological Malignancies • Leukemia • Oncology • Ovarian Cancer • Solid Tumor • LIF • LIFR • PTPRC

Significance of LIF/LIFR axis in the progression of inflammatory breast cancer (AACR 2024) - "Collectively, these studies demonstrated the therapeutic benefit of using EC359 to target the LIF/LIFR axis and opened the door for the development of new treatment approaches."

Breast Cancer • Estrogen Receptor Positive Breast Cancer • Hematological Malignancies • Hormone Receptor Breast Cancer • Inflammatory Breast Cancer • Leukemia • Oncology • Solid Tumor • Triple Negative Breast Cancer • IL6 • LIF • LIFR

Leukemia inhibitory factor (LIF)-factor XIIIA mediated macrophage-stromal crosstalk in pancreatic cancer (AACR 2024) - "This study delves into the potential regulatory pathway through which LIF induces remodeling of the ECM within the PDAC TME. We targeted LIF-induced macrophage-stromal crosstalk using the LIFR antagonist (EC359) in an orthotopically tumor implanted LSL-KrasG12D/+; Trp53 R172H/+; Pdx1Cre/+ (KPC) mice model of PDAC... Our investigation provides valuable insights into the possible mechanism by which LIF triggers ECM remodeling, thereby contributing to the desmoplastic stroma. Significantly, our findings propose that LIF-regulated FXIIIa signaling in macrophages serves as a plausible mediator of the LIF-induced ECM remodeling in PDAC."

Stroma • Gastrointestinal Cancer • Hematological Malignancies • Leukemia • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • F13A1 • KRAS • LIF • LIFR • TP53

Investigating the potential of EC359 in inducing ferroptosis for the treatment of type I and type II endometrial cancers (AACR 2025) - "In conclusion, our data indicate that EC359 is a potent inducer of ferroptosis in endometrial cancer cells and has the potential to be used as an additional tool in current endometrial cancer treatment regimens."

Endometrial Cancer • Gynecologic Cancers • Oncology • Solid Tumor • LIFR

Targeting the LIF/LIFR axis reduces the progression of inflammatory breast cancer by promoting ferroptosis (AACR 2025) - "Collectively, our research suggests that the inhibition of LIFR promotes ferroptosis-mediated cell death in IBC, and LIFR inhibitors represent a novel therapeutic option for IBC."

Breast Cancer • Inflammatory Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • GPX4 • LIFR • SLC7A11

Stromal transcriptomics uncover LIF as a key effector in high tumor budding triple-negative breast cancer. (PubMed, Sci Rep) - "The induction of TNBC cell migration and expression of programmed death-ligand 1 (PD-L1) by a recombinant LIF, along with attenuation by EC359, a LIF inhibitor, were investigated using Transwell assay and flow cytometry...FAP-positive CAFs overexpress genes like LIF, which promotes cell migration and PD-L1 expression. LIF inhibition reduces these effects, suggesting LIF as a potential therapeutic target in TB-associated TNBC progression and immunotherapy."

IO biomarker • Journal • Breast Cancer • Hematological Malignancies • Leukemia • Oncology • Solid Tumor • Triple Negative Breast Cancer • CAFs • CDKN1C • FAM83A • FAP • LIF • SLC26A2 • ZNF23

EC359 Enhances Trametinib Efficacy in Ras/Raf-Driven Ovarian Cancer by Suppressing LIFR Signaling. (PubMed, Biomolecules) - "Our studies identify LIFR signaling as a critical vulnerability in Ras/Raf-mutant and low grade serous OCa. Further, it provides strong preclinical rationale for EC359 and trametinib combination therapy as a new therapeutic strategy for treating Ras/Raf-driven OCa and low-grade serous OCa."

Journal • Gynecologic Cancers • Hematological Malignancies • Leukemia • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Solid Tumor • KRAS • LIF • LIFR

Emergence of conjugative metallo-β-lactamase-encoding plasmids in the Klebsiella pneumoniae species complex: First identification of IMP-8-MCR-9.1 in K. quasipneumoniae and VIM-1 in K. variicola in Taiwan. (PubMed, J Infect Public Health) - "We firstly report the presence of conjugative carbapenemase-carrying plasmids in Kq and Kv in Taiwan. The recombination and dissemination of these plasmids warrant close monitoring."

Journal • Infectious Disease • Pneumonia

LIF Receptor Inhibitor EC359 Impairs Proliferation of Hut78, HH and Jurkat Cell Lines| (EORTC-CLTG 2025) - No abstract available

Preclinical • Oncology • LIFR

Targeting cancer-associated fibroblast-driven LIF/LIFR axis improves the therapeutic efficacy of gemcitabine and nab-paclitaxel in pancreatic cancer. (PubMed, NPJ Precis Oncol) - "In autochthonous murine model of PDAC, EC359 enhanced the therapeutic efficacy of gemcitabine and nab-paclitaxel, accompanied by an increase in dendritic cells but a reduction in T-regulatory cells. Thus, EC359 reduces PDAC cell stemness, stabilizes microtubule assembly, and reduces the immunosuppressive microenvironment to improve the efficacy of standard-of-care in PDAC."

Journal • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CAFs • LIFR

Novel LIFR-targeted combination therapy to enhance the utility of standard-of- care chemotherapy in treating ovarian cancer (WAGO 2025) - "Methods The efficacy of the LIFR inhibitor EC359 in combination with paclitaxel and/or carboplatin was evaluated in established and chemotherapy resistant OCa cell lines, as well as in patient-derived xenograft (PDX) models. Ongoing investigations are exploring the therapeutic potential of EC359 in PDX models and its efficacy as a maintenance therapy for primary and resistant OCa. Conclusions This study provides convincing preclinical evidence supporting LIFR inhibition as a promising strategy to enhance the efficacy of chemotherapy in OCa, addressing critical challenges in chemoresistance and recurrence."

Combination therapy • Hematological Malignancies • Leukemia • Oncology • Ovarian Cancer • Solid Tumor • LIF • LIFR

Targeting the Leukemia Inhibitory Factor/Leukemia Inhibitory Factor Receptor Axis Reduces the Growth of Inflammatory Breast Cancer by Promoting Ferroptosis. (PubMed, Cancers (Basel)) - "EC359 (5 mg/kg/day) was effective in reducing the growth of the IBC KPL4 xenograft tumors. These findings demonstrates that LIFR inhibition promote ferroptosis-mediated cell death in IBC and that EC359 represent novel therapeutic for IBC treatment."

Journal • Breast Cancer • Hematological Malignancies • Inflammatory Breast Cancer • Leukemia • Oncology • Solid Tumor • GPX4 • LIF • LIFR

Significance of LIF/LIFR Signaling in the Progression of Obesity-Driven Triple-Negative Breast Cancer. (PubMed, Cancers (Basel)) - "RNA-Seq analysis identified critical pathways modulated by LIF/LIFR signaling in diet-induced obesity mouse models. These findings suggest that adiposity contributes to TNBC progression via the activation of the LIF/LIFR pathway, and LIFR inhibition with EC359 represents a promising therapeutic approach for obesity-associated TNBC."

Journal • Breast Cancer • Genetic Disorders • Hematological Malignancies • Leukemia • Obesity • Oncology • Solid Tumor • Triple Negative Breast Cancer • LIF • LIFR

Leukemia Inhibitory Factor Receptor inhibition by EC359 reduces atherosclerotic stenosis grade in Ldlr-/- mice. (PubMed, Eur J Pharmacol) - "Consequently, immune cell infiltration was reduced in aortic plaques of EC359 treated mice compared to control mice. Conclusively, we demonstrated that LIF receptor is a potential therapeutic target in atherosclerosis by reducing plaque size, attributed to lower serum cholesterol levels, reduced endothelial activation and less immune cell infiltration in the plaque."

Journal • Preclinical • Atherosclerosis • Cardiovascular • Dyslipidemia • Hematological Malignancies • Leukemia • Oncology • CD31 • IL6 • LIF • LIFR • PECAM1 • VCAM1

Pharmacological inhibition of the LIF/LIFR autocrine loop reveals vulnerability of ovarian cancer cells to ferroptosis. (PubMed, NPJ Precis Oncol) - "Additionally, EC359 therapy considerably improved tumor immunogenicity by robust CD45+ leukocyte tumor infiltration and polarizing tumor-associated macrophages (TAMs) toward M1 phenotype while showing no impact on normal T-, B-, and other immune cells. Collectively, our findings indicate that the LIF/LIFR autocrine loop plays an essential role in OCa progression and that EC359 could be a promising therapeutic agent for OCa."

Journal • Colorectal Cancer • Gynecologic Cancers • Hematological Malignancies • Leukemia • Oncology • Ovarian Cancer • Solid Tumor • LIF • LIFR • PTPRC

The LIFR Inhibitor EC359 Effectively Targets Type II Endometrial Cancer by Blocking LIF/LIFR Oncogenic Signaling. (PubMed, Int J Mol Sci) - "Tumor progression was markedly inhibited by EC359 treatment in two different patient-derived xenograft models in vivo and patient-derived organoids ex vivo. Collectively, these results suggest LIFR inhibitor EC359 as a possible new small-molecule therapeutics for the management of Type II ECa."

Journal • Endometrial Cancer • Gynecologic Cancers • Hematological Malignancies • Leukemia • Oncology • Solid Tumor • LIF • LIFR • STAT3

The LIFR-targeting small molecules EC330/EC359 are potent ferroptosis inducers. (PubMed, Genes Dis) - No abstract available

Journal • LIFR

Targeting leukemia inhibitory factor in pancreatic adenocarcinoma. (PubMed, Expert Opin Investig Drugs) - "Future research should focus on investigating LIF targets in combination with current standard-of-care chemotherapy, and immunotherapy can be a promising approach. Further, larger multicenter clinical trials are needed to define the use of LIF as a new biomarker in PDAC patients."

IO biomarker • Journal • Gastrointestinal Cancer • Hematological Malignancies • Leukemia • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • IL6