Researchers at the Biodonostia Health Research Institute reported on the role of KLF15 in cholangiocarcinogenesis and its potential as a therapeutic target in this disease.
Opioid use disorder (OUD) causes high morbidity and mortality rates, with fentanyl driving unprecedented overdose rates. Researchers from the University of California have used an AI-based drug discovery platform with the aim of identifying preclinical drug candidates for OUD.
Hepatoblastoma is the most common liver cancer during childhood, with limited therapeutic options in aggressive or relapsed cases. NEDDylation is a post-translational modification that modulates cullin-RING ligases and has arisen as a crucial regulator of protein turnover in cancer.
Serotonergic G-protein-coupled receptors (GPCRs), including the 5-HT2A receptor (5-HT2AR) and 5-HT2CR, are key regulators of cortical signaling pathways and promising targets for neurotherapeutic drug discovery. Researchers from the University of Texas System have developed AB-0124, a 5-HT2AR allosteric ligand, and JPC-0323, a dual 5-HT2AR/5-HT2CR allosteric ligand, with the aim of overcoming issues with direct agonists of these receptors for treating substance abuse disorders, like cocaine use.
Researchers at DEM Biopharma Inc. reported preclinical findings demonstrating the efficacy of DEM-301, a bifunctional antibody-drug conjugate (ADC) engineered to selectively recognize and eliminate tumor cells that express DEM-TXX.
Orexin OX2 receptor agonists have demonstrated the ability to enhance wakefulness in rodent models, as well as in nonhuman primates and patients with narcolepsy and idiopathic hypersomnia. Based on recent findings, it has been hypothesized that they may also regulate cognition, mood and other neuropsychiatric functions. Furthermore, dysregulated orexin signaling has been reported in patients with major depressive disorder (MDD) with suicide attempts.
About one-third of patients with major depressive disorder (MDD) are treatment resistant. Ketamine is very effective in treatment-resistant depression, but it is associated with psychotomimetic effects. Metabotropic glutamate mGlu2 and mGlu3 receptors negatively regulate the release of glutamate and are involved in the pathogenesis of depression.
Post-traumatic stress disorder (PTSD) is a condition with limited effective therapeutic options to date, where 5-HT2A receptor agonists show promise for enhancing cortical plasticity in the brain and aiming in the processing of trauma. Engrail Therapeutics Inc. has presented data for their 5-HT2A agonist and dopamine D2/D3 receptor antagonist neuroplastogen ENX-205 for the potential treatment of PTSD.
FGFR1 is a receptor tyrosine kinase that drives multiple intracellular signaling pathways involved in tumor cell proliferation, survival and progression. Because these pathways are frequently hyperactivated in colorectal cancer (CRC), FGFR1 represents a biologically relevant therapeutic target, and its inhibition has the potential to simultaneously suppress several oncogenic mechanisms.
Venetoclax has shown good results for adult acute myeloid leukemia (AML) in combination with azacitidine, but there is increasing evidence of inherent and acquired resistance. High expression of nicotinamide phosphoribosyltransferase (NAMPT) has been associated with cancer aggressiveness and poor prognosis due to increased nicotinamide metabolism.
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