The efficacy of cannabinoid CB1 receptor antagonists in diet-induced obesity and its related metabolic complications is well established, but they are tied to central nervous system (CNS)-related adverse effects due to brain penetration. There is increasing interest in developing peripherally restricted compounds for use in the clinic, but the molecular mechanisms behind the metabolic benefits from CB1 receptor antagonists is still poorly understood.
Large-scale human genetic studies have revealed that loss-of-function INHBE variants are associated with a lower abdominal to gluteofemoral fat ratio, improved metabolic profile, and reduced fasting glucose levels.
Von Willebrand factor (vWF) plays a crucial role in hemostasis, and elevated levels are associated with risk of thrombosis. Gain-of-function mutations in the C-domain of vWF are linked to an increased risk of thrombosis. Previous work has shown that disrupting cysteine-rich C-domain in vWF led to reduced platelet recruitment in a shear-dependent fashion, making it a promising target for pharmacology. Apollo Therapeutics Ltd. has presented data on antibodies targeting the C-domain of vWF, including AP-21 as antithrombotics.
Researchers from Oricell Therapeutics (Shanghai) Co. Ltd. presented the discovery and preclinical characterization of ORIC-613, a dual-targeting CAR T-cell therapy being developed for the treatment of pancreatic and gastric cancer.
Therapeutics for peripheral neuropathies, such as Charcot-Marie-Tooth (CMT) disease, are still quite limited and focus on managing symptoms. Augustine Therapeutics NV has presented an orally available histone deacetylase 6 (HDAC6) inhibitor, AGT-100216, for the treatment of CMT. AGT-100216 was designed to work through improving axonal regeneration and nerve functional restoration.
Cannabidiol (CBD) is a nonpsychoactive cannabinoid with potential therapeutic use in several diseases such as epilepsy or anxiety, but shows poor solubility, erratic absorption and structural polymorphisms that limit its bioavailability. Researchers from Artelo Biosciences Inc. presented the pharmacokinetic profile of ART12.11, a proprietary co-crystallization of CBD and co-former tetramethylpyrazine (TMP), formulated to achieve improved bioavailability and stability and to overcome polymorphism of CBD.
Researchers from the National Cancer Institute presented data from a study that aimed to explore the role of the major nuclear exporter protein exportin 1 (XPO1) in pancreatic neuroendocrine tumor (pNET) subsistence and therapy resistance.
Craniopharyngiomas are a rare brain cancer of the suprasellar region, and despite being benign tumors, their management can be challenging. Investigators from the Children’s Hospital of Philadelphia have aimed to identify transcriptional factors that may predict recurrence of craniopharyngiomas.
Beijing Gensciences Inc. has developed a FVIIIa-mimetic bispecific antibody named SS-315 for the treatment of hemophilia A. SS-315 was developed by targeting FX with its upper Fab arms and FIXa with its down-side scFv arms, respectively; the hemostatic potential of SS-315 was investigated in vitro and in vivo.
Researchers from the Johns Hopkins University School of Medicine have hypothesized that LP-184 could synergize with the PARP inhibitor rucaparib, which avoids DNA repairing in tumor cells, for the treatment of atypical teratoid rhabdoid tumor.
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