A5060585024- Phosphodiesterase function and regulation
- Air Quality and Health Impacts
- Calcium signaling and nucleotide metabolism
- Synthesis and Catalytic Reactions
- CRISPR and Genetic Engineering
- Peptidase Inhibition and Analysis
- PARP inhibition in cancer therapy
- Receptor Mechanisms and Signaling
- Ubiquitin and proteasome pathways
- Climate Change and Health Impacts
- Health, Environment, Cognitive Aging
Shanxi University
2024
Broad Institute
2022-2023
As a global problem, fine particulate matter (PM 2.5 ) really needs local fixes. Considering the increasing epidemiological relevance to anxiety and depression but inconsistent toxicological results, most important question is clarify whether how PM causally contributes these mental disorders which components are dangerous for crucial mitigation in particular place. In present study, we chronically subjected male mice real-world exposure system throughout winter heating period coal...
Abstract BAY 2666605, co-developed by the Broad Institute and Bayer Pharmaceuticals, is a selective potent molecular glue, part of family small molecules recently baptized as ‘velcrins’, that induces complex formation between phosphodiesterase 3A (PDE3A) SLFN12. 2666605 has entered First-in-Human study (NCT04809805) in patients with advanced solid tumors here we describe its pre-clinical pharmacology profile. DNMDP, precursor to was discovered phenotypic screen genomically annotated cancer...
Abstract Velcrin compounds are a class of small molecules that induce complex formation between PDE3A and SLFN12, killing cancer cells express elevated levels these two proteins by mechanism independent enzymatic inhibition. Instead, binding stimulates the RNase activity resulting in cleavage specific SLFN12 substrate, tRNA-Leu-TAA. Cleavage tRNA-Leu-TAA turn causes ribosomal pausing, inhibition protein synthesis, cell death. Unlike traditional targeted therapies leverage dependencies...
Abstract Velcrins are a novel class of compounds that kill cancer cells expressing elevated levels PDE3A and SLFN12. These induce PDE3A-SLFN12 heterotetramer complex formation, resulting in upregulation the RNase activity SLFN12 cleaves tRNA-Leu-TAA, which leads to inhibition global translation and, consequently, apoptosis sufficient both proteins. Uveal melanoma, type melanoma occurs eye, is genomically distinct from cutaneous melanoma. Whereas mutations BRAF, NRAS, KRAS, HRAS common uveal...