Bridged ring compound refers to any two rings in the compound, which share two non-directly connected carbon atoms, and are classified into bicyclic hydrocarbons, tricyclic hydrocarbons, tetracyclic hydrocarbons, etc. Carbon atoms used in two or more rings are bridgehead carbon atoms, and the bond connecting the bridgehead carbon atoms is called a bridge. Bridged ring compounds are a class of organic compounds that are widely present in nature and usually have important physiological activities, such as the famous anticancer drug paclitaxel and antimalarial drug artemisinin.
bridged compounds,bridged bicyclic compounds
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HRS-4642 is a high affinity, selective, long-acting, and non-covalent KRAS G12D inhibitor, with an affinity constant of 0.083 nM. HRS-4642 demonstrated robust efficacy against KRAS G12D-mutant cancers both in vitro and in vivo. Importantly, in a phase 1 clinical trial, HRS-4642 exhibited promising anti-tumor activity in the escalating dosing cohorts. Furthermore, the sensitization and resistance spectrum for HRS-4642 was deciphered through genome-wide CRISPR-Cas9 screening, which unveiled proteasome as a sensitization target. HRS-4642, either as a single agent or in combination with carfilzomib, reshaped the tumor microenvironment toward an immune-permissive one.
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