Proto-oncogene tyrosine-protein kinase receptor Ret is a widely expressed oncogene and chromosomal rearrangements involving RET lead to fusion genes and RET kinase activation, which occur in lung cancer in about in 2% of cases of non-small cell lung cancer.
Efforts at Abbvie Inc. to selectively target voltage-gated sodium channel subunit alpha Nav1.7 to treat pain led to the discovery of quinoline and quinolone agents and, through structure-activity relationship studies, the candidate product ABBV-318. While Nav1.7 potency could be achieved with earlier compounds, efforts were required to improve characteristics including hERG activity, pharmacokinetics and selectivity over Nav1.5, yielding compounds which blocked Nav1.7 as well as another target for treating pain, Nav1.8.
Researchers from Arbutus Biopharma Corp. presented preclinical data for the novel hepatitis B virus (HBV) capsid assembly inhibitor, AB-836, being developed for the treatment of chronic HBV infection.
To target mutant RAS in the GTP-bound RAS(ON) state for cancer treatment, Revolution Medicines Inc. has developed a platform in which binding and inhibition occur through small molecule-driven formation of a high-affinity ternary complex (tri-complex) between the target protein, a small molecule and a chaperone such as cyclophilin A.
Researchers from Italfarmaco SpA presented a new class of highly selective histone deacetylase 6 (HDAC6) inhibitors as potential candidates for the treatment of several pathologies, such as autoimmune disorders, neurodegenerative diseases, and cancer.
Structure-guided design for carbazole antagonists of Toll-like receptors 7 and 8 (TLR7/8) for the potential treatment of autoimmune disorders was reported by Bristol Myers Squibb Co. TLR activation can induce proinflammatory pathway activation, which has been identified in patients with lupus.
The Massachusetts Institute of Technology (MIT) has developed collagen mimetic peptides for PET imaging to detect idiopathic pulmonary fibrosis (IPF), with [68Ga]DOTA-CMP showing selective identification of fibrotic collagen in vivo.
Researchers from Pfizer Inc. presented preclinical data for the melanocortin MC4 receptor (MC4R) antagonist PF-07258669, being developed for the treatment of anorexia nervosa.
Circadian rhythm disorders are associated with psychiatric disorders including depression, bipolar disease and schizophrenia. To target casein kinase I isoform delta (CKI-delta), Janssen Pharmaceutica NV scientists sought potent, selective, brain-penetrant CKI-delta inhibitors which can be dosed daily and orally.
