Dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) is an attractive therapeutic target due to its involvement in cancer and neurodegenerative diseases. Researchers from the National Health Research Institutes and their collaborators have presented a series of DYRK1A inhibitors for reducing neurofibrillary tangle formation in Alzheimer’s disease.
Cannabinoid CB1 receptors have been a potential target for nonopioid-based pain treatment, but actually targeting the pathway has been hindered by issues with tolerance and unwanted CNS side effects. Peripherally selective CB1 agonists developed to overcome these problems have not fully resolved these issues, meaning the peripheral selectivity has to be substantially enhanced.
Researchers from the University of Queensland recently provided details on the discovery and preclinical characterization of a new hematopoietic prostaglandin D2 synthase (HPGDS) inhibitor, CLS-189, being developed for the treatment of Duchenne muscular dystrophy (DMD).
Histone deacetylase 3 (HDAC3) is involved in transcriptional regulation, phosphorylation and the inhibition of tumor suppressor genes. Its upregulation in several types of tumors, such as colorectal, prostate, breast and ovarian cancers, among others, makes it a potential therapeutic target in cancer.
Researchers from Ileadbms Co. Ltd. presented the discovery and preclinical characterization of IL-21120033, a new CXCR7 agonist being developed for the treatment of inflammatory bowel disease.
Targeted protein degradation (TPD) is an alternative to conventional protein inhibition that is gaining attention due to advantages such as ensuring complete elimination of the target protein, reduced off-target effects or the potential to target previously inaccessible or “undruggable” proteins. Proteolysis targeting chimeras (PROTACs) are agents used for TPD that have proven effective for degradation of histone deacetylase (HDAC), among other different proteins.
Right open reading frame kinase 2 (RIOK2) plays an essential role in ribosome assembly and cell growth, survival and stress responses. Research has linked RIOK2 to tumor progression and poor prognosis in several types of cancer such as breast, lung, prostate or hematological tumors.
The absent, small or homeotic-like 1 (ASH1L) protein regulates the expression of HOXA genes, which are critical for the development of MLL1 translocations frequently found in leukemia patients. Knockdown of ASH1L leads to growth arrest and apoptosis of leukemia cells, thereby inhibiting leukemia progression suggesting that ASH1L can be considered as a therapeutic target in this setting.
Hypoxia-inducible factors (HIFs) are crucial to maintain oxygen homeostasis by regulating cellular metabolic adaptation under hypoxia conditions. Depletion of factor inhibiting HIF (FIH), an enzyme that negatively regulates the activity of the HIF-1α isoform, has been associated with reductions in hepatic steatosis and body mass in mice.
Tyrosine-protein phosphatase non-receptor type 1 (PTP1B) acts as a negative regulator of the insulin signaling pathway by dephosphorylating both the insulin receptor (IR) and the insulin receptor substrate, leading to insulin resistance, the most significant characteristic of type 2 diabetes.
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