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.
The inhibition of cyclin-dependent kinase 4 (CDK4) and CDK6 is a useful strategy to treat hormone receptor (HR)+/HER2+ breast cancer, but patients may develop resistance through different mechanisms. As reported at the recent San Antonio Breast Cancer Symposium, researchers from Biotheryx Inc. have synthesized a new CDK4/6 degrader – BTX-9341 – to address the problem of therapeutic resistance in breast cancer.
Researchers from Medical University of South Carolina aimed to evaluate the potential of secreted frizzled-related protein 2 (SFRP2) as a promising novel target for breast cancer using a newly developed humanized monoclonal antibody to SFRP2 (hSFRP2 MAb) in models of this disease.
University of Oxford scientists have presented data from deep proteomics of cerebrospinal fluid (CSF) in search of proteins with diagnostic or prognostic value in amyotrophic lateral sclerosis (ALS). Analysis was performed using CSF samples from 40 ALS patients, 15 controls (healthy individuals) and 8 mimicking conditions.
Researchers from Autifony Therapeutics Ltd. presented preclinical data for the novel potent Kv3 channel positive modulator, AUT-00201, which is currently being evaluated in early clinical studies for the treatment of patients with progressive myoclonus epilepsy type 7 (EPM7).
Microtubule acetylation and impaired axonal transport have been proposed as mechanisms causing amyotrophic lateral sclerosis (ALS). Furthermore, histone deacetylase 6 (HDAC6) is known to play a role in acetylation of α-tubulin, a subunit of microtubules. ACY-738 is an HDAC6 inhibitor that has been reported to slow neuron degeneration in Alzheimer’s disease and ALS models by increasing acetylation of α-tubulin.
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.
It is known that heterozygous mutations in the HBB gene, which encodes β-globin, are the cause of inherited β-thalassemia. A new case report describes a novel frameshift mutation in the HBB gene leading to a dominant form of β-thalassemia.