A new degrader strategy has been previously proposed to mitigate platelet toxicity associated with Bcl-xL degraders. This strategy consists of selectively degrading Bcl-xL by the von Hippel-Lindau protein (VHL) E3 ligase in tumor cells, but not in platelets, which minimally express VHL. DT-2216 was developed as the first Bcl-xL degrader of this kind; however, this clinical candidate has still shown some platelet toxicity in vivo.
Psychiatric indications, such as depression, schizophrenia and bipolar disorder, share a common feature of elevated expression of pro-inflammatory markers in the periphery and/or central nervous system. Based on this, it is believed that combined immuno- and neuromodulatory activities of phosphodiesterase 4 (PDE4) inhibitors may represent a promising new therapeutic strategy for various psychiatric indications.
Nuclear receptor subfamily 1 group D member (NR1D1), also known as Rev-erbA-α, is highly expressed in the liver, adipose tissue, brain and skeletal muscle.
Trypto Therapeutics GmbH scientists have discovered novel tryptophan hydroxylase (TPH) inhibitors, which are being developed for the treatment of colorectal cancer.
Organophosphorus compounds (OPs) include several types of chemical compounds used as pesticides, herbicides or nerve agents in chemical warfare that, once in the body, act by inhibiting acetylcholinesterase (AChE) functions leading to an excessive increase of acetylcholine that ultimately causes death after respiratory failure.
Norcantharidin is an active ingredient in Chinese traditional medicine that has activity against several cancer types, but its application is limited in the clinic due to toxicity and a narrow treatment window. Researchers from Tongji University and the Shanghai Institute of Materia Medica have recently described a derivative of norcantharidin – DCZ-5417 – for the potential treatment of multiple myeloma (MM).
Researchers from Multitude Therapeutics Inc. have reported the preclinical profile of AMT-253, a MUC18-targeting antibody-drug conjugate (ADC) under development for the treatment of melanoma. It comprises the anti-MUC18 humanized antibody pAb253-H linked to T1000 exatecan payload and showed superior antitumor efficacy than the traditional vc-MMAE-based ADC AMT-253-M.
Researchers at Dana-Farber Cancer Institute are advancing a fourth-generation allosteric EGFR inhibitor, EAI-432, to treat non-small-cell lung cancer driven by mutations in the EGFR gene, particularly the L858R mutation.
In stroke, one of the events underlying neuronal injury is the interaction of neuronal nitric oxide synthase (nNOS) with postsynaptic density protein 95 (PSD-95) leading to nitric oxide overproduction.
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.webp?height=488&t=1677877909&width=650 "Epidermal growth factor receptor (EGFR)")
