Heart failure with preserved ejection fraction (HFpEF) is a complex disease with limited therapeutic options. Protein histone deacetylase 6 (HDAC6) is known to be involved in several biological processes, such as autophagy or inflammation, among others, but its impact on HFpEF has not been well evaluated to date.
METTL3, the enzyme that adds the m6A RNA modification, is a key regulator of RNA processing and protein synthesis. In cancer, METTL3 is often overexpressed, driving tumor growth, invasion and therapy resistance across multiple malignancies, including lung, pancreatic, ovarian, colorectal cancers and acute myeloid leukemia.
Schizophrenia is a complex psychiatric disorder marked by positive, negative and cognitive symptoms, many of which are poorly addressed by current dopamine-blocking antipsychotics. Preclinical studies show that muscarinic acetylcholine M4 receptor positive allosteric modulators (M4 PAMs) can reduce hyperdopaminergic activity and improve both positive and negative symptom-related behaviors, suggesting they may offer enhanced antipsychotic efficacy with improved tolerability.
The limited efficacy of cancer immunotherapy is usually attributed to suboptimal antitumor T-cell generation, as well as impaired immunological memory development. MDX-2004 is a trispecific antibody-fusion protein developed by Modex Therapeutics Inc. that targets CD3, CD28 and CD137 on human T cells, which was designed to overcome these limitations by rejuvenating the immune system and enhancing antitumor immunity.
At the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, researchers from Circle Pharma Inc. presented their recent work on developing novel compounds that specifically target cyclin D1 while avoiding the toxicity associated with targeting cyclin D3.
Researchers from Chantibody Therapeutics Inc. presented the preclinical characterization of CT-111, a trispecific antibody engineered to simultaneously target PD-1, CTLA-4, and VEGF.
Arginase 1 (Arg1) is a key mediator of immune suppression, and its overexpression has been reported in multiple cancers, including renal cell carcinoma, pancreatic cancer, and head and neck cancer. However, clinical strategies aimed at inhibiting Arg1 function have achieved only limited success.
At the 2025 annual meeting of the Society for Neuroscience in San Diego this week, Catherine Woolley’s plenary lecture was an unusual combination of debunking and affirming the importance of sex differences in the brain.
Although tricomplex pan-RAS (ON) inhibitors, such as RMC-6236, constitute a promising class of therapeutics against RAS-driven cancers, their on-target, off-tumor toxicities challenge the dosing strategy and the safety of drug combinations.
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