Solu Therapeutics Inc. has identified heterobifunctional cotinine-containing compounds acting as sodium channel protein type 10 subunit α (SCN10A; Nav1.8) blockers or sodium channel protein type 9 subunit α (SCN9A; Nav1.7) blockers. They are reported to be useful for the treatment of pain, cough and pruritus.
Jiangsu Hengrui Pharmaceuticals Co. Ltd.; Shanghai Hengrui Pharmaceutical Co. Ltd. have synthesized antibody-drug conjugates (ADCs) comprising a claudin 6 (CLDN6)-targeting antibody linked to cytotoxic drug through linker. They are described as potentially useful for the treatment of ovarian cancer.
Merck KGaA has reported proteolysis targeting chimera (PROTACs) comprising an E3 ubiquitin ligase-binding moiety covalently linked to mitogen-activated protein kinase kinase kinase kinase 1 (MAP4K1; HPK1; MEKKK1)-targeting moiety. They are described as potentially useful for the treatment of cancer.
Nippon Shinyaku Co. Ltd. has disclosed compounds inhibiting binding between r(CUG) repeats in DMPK (DM1) and MBNL protein reported to be useful for the treatment of myotonic dystrophy 1.
Positive allosteric modulators (PAMs) of the muscarinic acetylcholine M4 receptor show potential against schizophrenia because they can enhance endogenous acetylcholine signaling, which in turn may mitigate psychotic symptoms as well as improve attention and working memory in individuals with the disorder. However, the efficacy of a promising PAM, CVL-231, has been disappointing in clinical trials.
In idiopathic pulmonary fibrosis, the lung tissue thickens and stiffens through proliferation of fibroblasts and invasion by inflammatory cells. One of the drivers of these processes is the enzyme autotaxin, which produces the signaling molecule lysophosphatidic acid. Several inhibitors of autotaxin have been reported, which show varying degrees of clinical potential.
Anti-inflammatory compounds can alleviate many acute and chronic diseases, including autoimmune, cardiovascular and neurodegenerative disorders. However, many such compounds increase risk of numerous adverse events because they inhibit not only cyclooxygenase-2 (COX-2), which induces pathological inflammation, but also COX-1, which is important for renal and gastrointestinal function.
The enzyme PARP1 helps repair single-stranded DNA breaks, and its inhibition shows antitumor efficacy in ovarian, breast, prostate and pancreatic cancers involving mutations in BRCA1 or BRCA2. However, resistance to PARP1 inhibition is a major problem.
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