Azetidines are an important class of saturated four-membered nitrogen-containing heterocyclic compounds. The research hotspots related to this structure mainly focus on two aspects: one is the research of pharmaceutical chemistry; the other is related to chiral azetidines, using rigid azetidine compounds as chiral ligands for asymmetric catalytic reactions. Many nitrogen-containing heterocycles play important roles in drug structures, and in many cases small structural changes can improve ligand selectivity and pharmacokinetic properties.
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Olema Oncology is advancing the development of Palazestrant (OP-1250) in metastatic breast cancer in 2024. Palazestrant is an oral complete ER antagonist (CERAN) and selective ER degrader (SERD). It potently binds and completely blocks transcriptional activity of both wild-type and ESR1-mutant ER with favorable tolerability and anti-tumor activity.
Palazestrant is under clinical development both in combination with Novartis' CDK4/6 inhibitor Kisqali (Ribociclib) as a first-line therapy for advanced estrogen receptor-positive, HER2-negative breast cancer, and as a monotherapy compared to standard of care treatment in second- and third-line advanced or metastatic ER-positive, HER2-negative breast cancer.
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