tyroserleutide (CMS024) / China Medical System - LARVOL DELTA

JiguCao capsule alleviates metabolic dysfunction-associated steatotic liver disease through modulation of gut-liver axis and toll-like receptor 4 signaling (EASL 2026) - "This study aimed to elucidate the therapeutic mechanisms of JCF in MASLD, with particular focus on LPS-TLR4 signaling and gut-liver axis homeostasis.The funding for this study was sourced from the World Federation of Chinese Medicine Societies (targeted entrustment), with project numbers WFCMS2024026 and WFCMS2024027... JiguCao capsule ameliorates MASLD progression through TLR4-dependent suppression of hepatic inflammation, restoration of gut-liver axis homeostasis, and modulation of lipid metabolism. These findings provide mechanistic insights supporting the therapeutic potential of JCF as a multi-target intervention for MASLD."

IO biomarker • Hepatology • Inflammation • Liver Failure • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • CLDN1 • MYD88 • OCLN • TLR4

Artificial Tyroserleutide Transporters for Synergistic Cancer Therapy. (PubMed, JACS Au) - "Notably, 5F-C12, which functions as a molecular tweezer, forms a stable 1:1 complex with the charge-neutral peptide tyroserleutidean anticancer agent currently in Phase III clinical trialsand actively facilitates its transmembrane transport by shielding it from the membrane's hydrophobic core, achieving an EC50 value of 7.5 μM. For the first time, 5F-C12 could remarkably enhance the peptide's bioavailability and exhibit a pronounced enhanced anticancer effect against MCF-7 breast cancer cells both in vitro and in vivo."

Journal • Breast Cancer • Oncology • Solid Tumor

Endogenous Nanoplatforms for Tumor Photoimmunotherapy: Hypoxia Modulation and STING Pathway Activation. (PubMed, Acta Biomater) - "Its composition plays different roles: i) Biliverdin can induce mild photothermal and photodynamic therapy, enhance the penetration of nanoplatforms into tumors, and induce immunogenic cell death; ii) the immunotherapy peptide tyroserleutide induces tumor cell apoptosis and enhances tumor-specific immune responses; iii) Mn²⁺ can catalyze the generation of oxygen from hydrogen peroxide, reducing tumor hypoxia, while activating the cGAS-STING pathway, further boosting cancer immunotherapy...Additionally, it exhibits photoacoustic and magnetic resonance imaging capabilities, showing broad potential for precision cancer treatment guided by multimodal imaging. It has the potential to overcome the current limitations of photoimmunotherapy, offering a new avenue for cancer treatment."

Journal • Oncology

Identification of potent TMPRSS4 inhibitors through structural modeling and molecular dynamics simulations. (PubMed, Sci Rep) - "Therefore, this study aims to disover potential TMPRSS4 inhibitors that have better binding affinity than the approved inhibitors: 2-hydroxydiarylamide and tyroserleutide...Moreover, through a systematic analysis, MD simulations and MM-GBSA binding free energy calculations revealed that the best candidates Ergotamine, S55746, NPC478048, Lifirafenib, and NPC77101 are highly stable drug candidates in complex with TMPRSS4, displaying low RMSD and RMSF values with strong binding stability. Among these compounds, Ergotamine showed the most favorable binding energy (-33.73 kcal/mol). Overall, our in silico results revealed that these compounds could act as potent TMPRSS4 inhibitors and need to be validated by future experimental studies."

Journal • Infectious Disease • Novel Coronavirus Disease • Oncology • Respiratory Diseases • TMPRSS4

Effective Antitumor of Orally Intestinal Targeting Penetrating Peptide-Loaded Tyroserleutide/PLGA Nanoparticles in Hepatocellular Carcinoma. (PubMed, Int J Nanomedicine) - "Hematoxylin-eosin staining did not show any histological changes in the major organs. To summarize, YSL-PLGA/R6LRVG NPs could be a useful oral delivery system of YSL and may provide a new platform for the oral delivery of anticancer drugs."

Journal • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Oncology • Pain • Solid Tumor

Effect and mechanism of action in vitro of cyclodextrin derivative nanoparticles loaded with tyroserleutide on hepatoma. (PubMed, Nanotechnology) - "On the other hand, YSL/R6RGD-CMβCD NPs were not toxic for normal cells. Taken together, our results indicated that R6RGD-CMβCD could be considered as a nanopharmaceutical material with good tumor targeting abilities, and their combination with YSL could represent an effective anti-cancer system."

Journal • Preclinical • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Liver Cancer • Oncology • Solid Tumor

Self-assembly supramolecular drug delivery system for combination of photodynamic therapy and chemotherapy. (PubMed, J Microencapsul) - "This self-assembly supramolecular DDS can be used for combination of photodynamic therapy and chemotherapy in future research."

Journal • Oncology

pH-Triggered Conformational Change of Antp-Based Drug Delivery Platform for Tumor Treatment with Combined Photothermal Therapy and Chemotherapy. (PubMed, Adv Healthc Mater) - "In this study, AMP-based nanoparticles (AMP-NPs) conjugated with tyroserleutide (YSL), an immunologically therapeutic tripeptide, are designed to encapsulate doxorubicin (Dox) and indocyanine green (ICG) to improve cellular uptake and cancer therapeutic efficacy by combining chemotherapy with photothermal therapy. In a mouse xenograft model using H22 cells, tumors are ablated when Dox- and ICG-loaded AMP-NPs are injected with the combination of hyperthermia effect induced by near-infrared (NIR) laser irradiation and chemotherapy from Dox and YSL. The pH-, photothermal-, and glutathione-responsive AMP-NPs with a conformational transition strategy can be utilized to synergistically enhance the cancer therapeutic efficacy with few side effects upon NIR laser irradiation."

IO Biomarker • Journal • Hepatology • Oncology

Study of tyroserleutide for injection in hepatocellular carcinoma (HCC) patients (clinicaltrials.gov) - P3, N=300; Recruiting -> Enrolling by invitation

Recruiting status • Hepatocellular Cancer

Inhibitory Effects of Multivalent Polypeptides on the Proliferation and Metastasis of Breast Cancer Cells. (PubMed, ACS Med Chem Lett) - "To overcome this limitation, we attached the peptide tyroserleutide (YSL) to a molecular scaffold in order to produce homogeneous monovalent, bivalent, tetravalent, and octavalent YSL dendrimers with highly ordered secondary structures...Compared with monovalent YSL, the multivalent YSL dendrimers displayed enhanced in vivo antitumor activity and suppressed tumor growth and metastasis in BALB/c mice bearing 4T1 tumors. These findings indicate that multivalence can significantly enhance ligand potency and represent a potential method for the development of peptide drugs with high therapeutic potential."

Journal