LY2109761

To address this, an intelligent and injectable thermo-responsive hydrogel delivery system (LY@CNSG) constructed from cyclodextrin nanosponges and poly(N-isopropylacrylamide) was developed, in response to immunosuppressive prostaglandin E2 (PGE2) levels for autonomously controlling the release of LY2109761 (LY, a TGF-β inhibitor) based on competitive host-guest interaction. In triple-negative breast cancer models, photodynamic therapy combined with LY@CNSG significantly inhibited tumor growth and lung metastasis while enhancing antitumor immune activity. Furthermore, by integrating nitric oxide (NO)-responsive fluorescent probes, we created an integrated hydrogel platform, CYNH2-LY@CNSG, for simultaneous immunomodulator delivery and immune signaling molecule monitoring, providing a novel insight for biomarker monitoring and a more precise immunotherapy paradigm.

The MBRG-based model effectively predicts BLCA prognosis, integrates mechanisms of basement membrane remodeling, EMT, and immune suppression, and identifies DDR2 and SERPINF1 in CAFs as potential targets for personalized therapy.

To address these challenges, we develop a liposomal nanodrug that co-encapsulates a mitochondrial-targeted photosensitizer (MP) and a TGF-β receptor inhibitor (LY2109761) to synergize PDT with PD-1 checkpoint blockade...In murine PDAC models, this dual-action strategy transforms the immune-cold TME into an immune-inflamed phenotype, sensitizing tumors to PD-1 therapy and leading to pronounced tumor regression and prolonged survival. Our findings present a promising nanodrug-based approach to remodel the fibrotic and immunosuppressive TME of PDAC and enhance immunotherapeutic outcomes.

CD44 was knocked down in claudin‑low breast cancer cell lines (SUM159 and MDA‑MB‑231), and the TGF‑β receptor (TGFBR) inhibitor LY2109761 (LY‑61) was applied for treatment...Although CD44 depletion may increase EMT‑related signaling, invasion was primarily suppressed by TGF‑β blockade, and the combination with CD44 knockdown further enhanced the inhibition of proliferative phenotypes compared with either treatment alone. This dual‑targeting approach warrants further investigation in claudin‑low breast cancer.

The activation of the TGF-β/SMAD pathway and its interaction with the DNA repair via through ATR transductor was demonstrated. LY2109761 could act as a radiosensitizer for BNCT.

Human LUAD cells HCC827 and H1975 were exposed to different doses of osimertinib or erlotinib to generate TKI-resistant cell lines. Notably, the LY2109761 treatment reduced TKI resistance and diminished expansion, migration, and stemness in cancer cells induced by EMP3 overexpression. In conclusion, this study indicates that EMP3, upregulated upon EMT, contributes to EGFR-TKI resistance in LUAD cells.

The present research was designed to explore the impact of TGF-β1 inhibitors (LY2109761 and LY3200882) with or without gemcitabine on bladder cancer cells and to develop Pluronic F-127-based microspheres (MSs) for drug delivery. Systemic and local bladder toxicity assessments in mice demonstrated the in vivo safety of drug-loaded MSs. This study concludes that combining TGF-β1 inhibitors with gemcitabine in Pluronic F-127-based MSs enhances therapeutic efficacy against bladder cancer, promoting apoptosis, inhibiting cell invasion, and reducing tumor growth and metastasis while maintaining safety.

Here, we evaluated combination treatments using experimental TGFR inhibitors (TGFβi), SB525334 (SB), and LY2109761 (LY) with paclitaxel (PTX) chemotherapy. Genetic profiling of the tumors revealed differences in the expression levels of genes associated with TGFβ, epithelial to mesenchymal transition (EMT), TLR-4, and Bcl2 signaling, alluding to the susceptibility to specific gene signatures to the treatment. Taken together, our study suggests that TGFβi and PTX combination therapy using high-capacity POx micelle delivery provides a robust antitumor response in multiple TNBC subtype mouse models.

Activation of the TGFβ/Smad signaling pathway was found involved in AMIGO2-induced EMT, and treatment with the TGFβ receptor inhibitor LY2109761 suppressed AMIGO2-induced EMT...These results suggest that the nuclear translocation of AMIGO2 induces EMT to promote CRC invasion by activating the TGFβ/Smad signaling pathway. Thus, AMIGO2 is an attractive therapeutic target for inhibiting EMT and metastatic CRC progression.

To elucidate the underlying mechanism, we compared the efficacy of PFD after pretreatment with either TGF-β1 or a TGF-β receptor inhibitor (LY2109761). Additionally, PFD combined with cisplatin targeted TGF-β1 to inhibit glycolysis during EMT and enhanced the chemosensitization of A549 and H1299 cells. The magnitude of the anticancer effect exhibited by PFD was intricately linked to its metabolic properties.

The TGF-β1 signaling was interfered by LY2109761, a TGF-β receptor 1 (TβR1) inhibitor, or TGF-β1 neutral antibody...IFT88 siRNA or KIF3a siRNA impaired PC formation resulted in an aggravated DNA damage in bystander cells, while elevated PC formation by CytoD or STIL siRNA resulted in a decrease of DNA damage. Furthermore, TGF-β1 induced more DNA damages in S phases cells which showed lower PC formation rate and less DNA damages in G /G phase cells which showed higher PC formation rate. This study demonstrates the particular role of primary cilia during RCM induced DNA damages through TGF-β1 signaling restriction and thereby provides a functional link between primary cilia and RIBEs.

Collectively, although TEXs lead to the initial activation of CAR T-cells, the effect of TEXs suppressed CAR T-cells, which can be rescued by LY2109761. A treatment regimen combining CAR T-cell therapy and TGF-β inhibitors might be a novel therapeutic strategy for refractory and relapsed B-cell lymphoma.