Genes that are switched on or off in the human brain differ between men and women. Moreover, these differences are not uniform. They vary across cortical regions and cell types. Scientists at the National Institute of Mental Health (NIMH) and the National Institute on Aging (NIA) used single-cell sequencing and unveiled distinct gene expression patterns regulated by hormones and sex chromosomes. This detailed map of the brain’s molecular biology shows how women and men switch on and off more than 3,000 brain genes differently and expands the catalogue of X chromosome genes that escape inactivation. Read More
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. Read More
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. Read More
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. Read More
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. Read More
Hyperuricemia is defined as elevated uric acid levels in serum, usually exceeding 6.8 mg/dL, and the primary pathological cause of gout. Chinese investigators have reported recent results on the urate transporter 1 (URAT1) inhibitor HYJ-2 for the potential treatment of hyperuricemia. Read More
Researchers from the Government College University Faisalabad reported the discovery and preclinical characterization of IMS-48, a benzimidazole analogue designed to inhibit both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Read More
K2 Medicines (Nanjing) Co. Ltd. has identified new proteolysis targeting chimera (PROTAC) compounds comprising an E3 ubiquitin ligase-binding moiety coupled to a cyclin-dependent kinase 4 (CDK4)- and/or CDK4/6 dual-targeting moiety. They are designed for use in the treatment of cancer, neurodegeneration, viral infection, cardiovascular and inflammatory disorders. Read More
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. Read More
Resother Pharma ApS has divulged new N-formyl peptide receptor 2 (FPR2; FPRL1; LXA4) agonists potentially useful for the treatment of chronic inflammation. Read More
Ascletis Pharma (China) Co. Ltd. has patented new 2-phenyl-1,2,4-triazine-3,5(2h,4h)-dione derivatives acting as thyroid hormone receptor β (THR-β) agonists potentially useful for the treatment of diabetes, obesity, hyperlipidemia, fibrosis, hepatic steatosis, thyroid cancer and hypercholesterolemia, among others. Read More
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. Read More
