A Beone Medicines I GmbH and Beone Pharmaceutical (Suzhou) Co. Ltd. patent details new proteolysis targeting chimera (PROTAC) compounds comprising an E3 ubiquitin ligase-binding moiety coupled to an interleukin-1 receptor-associated kinase 1 (IRAK-1)- and IRAK-4-targeting moiety. They are described as useful for the treatment of cancer, inflammatory disorders and autoimmune diseases.
Recent evidence has suggested that secreted L-amino-acid oxidase, also known as interleukin-4-induced protein 1 (IL4I1), is involved in aromatic amino acid metabolism, as a key immunosuppressive enzyme expressed by tumor-associated myeloid cells, thus suppressing T-cell activation and proliferation within the tumor microenvironment.
Syracuse University recently presented a comprehensive preclinical program describing the rational design and optimization of peptide antagonists targeting the GDF15/GFRAL/RET receptor complex to mitigate nausea, emesis, anorexia and wasting associated with chemotherapy-induced stress signaling.
Mixed lineage kinase domain-like pseudokinase (MLKL), a key effector of necroptosis, is highly expressed in hepatocellular carcinoma (HCC), and its targeting may promote parthanatos-mediated immunogenic cell death. Researchers from the Chinese Academy of Sciences and collaborators described the discovery and preclinical characterization of C-116, a MLKL PROTAC degrader developed using AI-assisted rational drug discovery.
Cisplatin is widely used in chemotherapy regimens for many solid tumors, yet its therapeutic benefit is counterbalanced by significant toxicity and immunologically related limitations. Researchers from Jiangxi University of Chinese Medicine described the preclinical efficacy of the PD-L1-targeted cisplatin prodrug MN42-81, designed to overcome these limitations.
Signal transducer and activator of transcription 3 (STAT3) is a central mediator of cytokine and growth factor signaling and is aberrantly activated in approximately 70% of human cancers. Persistent STAT3 signaling drives tumor proliferation, survival, metastasis, angiogenesis, immune evasion and inflammation. Researchers from the University of Michigan reported the discovery and preclinical characterization of SD-965, a selective STAT3 PROTAC degrader.
Cogent Biosciences Inc. has discovered new tyrosine-protein kinase JAK2 V617F (JH2 domain) inhibitors potentially useful for the treatment of cancer and myeloproliferative diseases.
Accutar Biotechnology Inc. has synthesized new protein-protein interaction targeted chimera (PPI-TAC) compound comprising an E3 ubiquitin ligase-binding moiety covalently bound to a phosphatidylinositol 3-kinase α (PI3Kα)-targeting moiety. They act as PI3Kα H1047R mutant degradation inducers potentially useful for the treatment of cancer.
U.S. researchers have published data regarding IVMT-Rx-4, a melanoma differentiation-associated gene-9 (MDA-9) inhibitor with potential to treat bone-metastatic prostate cancer.
CSPC Pharmaceutical Group Ltd.’s SYS-6051 has gained clinical trial clearance from China’s National Medical Products Administration (NMPA) for advanced solid tumors. SYS-6051 is a human tissue factor-targeted antibody-drug conjugate that binds to tissue factor expressed on the surface of tumor cells.
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