Ren, Chaowei published the artcileStructure-based discovery of SIAIS001 as an oral bioavailability ALK degrader constructed from Alectinib, Name: tert-Butyl piperidin-4-ylcarbamate, the main research area is anaplastic lymphoma kinase alectinib preparation anticancer oral bioavailability; Alectinib; Anaplastic large-cell lymphomas; Anaplastic lymphoma kinase; CRBN; Oral bioavailability; Proteolysis targeting chimeras.
Fusion proteins of the anaplastic lymphoma kinase (ALK) are promising therapeutic targets for cancer and other human diseases, especially for non-small cell lung cancer (NSCLC) and anaplastic large-cell lymphomas (ALCLs). Herein a structure-based design, synthesis, and evaluation of ALK PROTACs (proteolysis-targeting chimeras) based on Alectinib, as the warhead were described. CRBN ligands as the E3 ligase moiety were screened first, used to obtain a series of potent ALK degraders based on different CRBN ligands, and exemplified by SIAIS091 and SIAIS001 with lenalidomide/thalidomide-based linkers. Both of them induced effective ALK degradation at low nanomolar concentrations in cells, and showed much better growth inhibition effects than Alectinib. SIAIS091 or SIAIS001 also promoted cell cycle arrest in G1/S phase. Finally, SIAIS001 exhibited good oral bioavailability in Pharmacokinetics study.
European Journal of Medicinal Chemistry published new progress about Anaplastic large-cell lymphoma. 73874-95-0 belongs to class piperidines, name is tert-Butyl piperidin-4-ylcarbamate, and the molecular formula is C10H20N2O2, Name: tert-Butyl piperidin-4-ylcarbamate.
Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem