Indole is a compound of pyrrole and benzene in parallel, also known as benzopyrrole. There are two combinations of pyrrole and benzene, called indole and isoindole, respectively. Many derivatives of indole have physiological and pharmacological activities, and can synthesize vasodilators, antihistamines, antipyretic analgesics, etc. in medicine, so indole is also a very important heterocyclic compound.
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Giredestrant (GDC-9545) is under development by Roche/Genentech. Giredestrant is a potent, next generation investigational selective oestrogen receptor (SERD) with best-in-class potential. In the phase 2 coopERA trial, postmenopausal patients with untreated ER+/HER2- early breast cancer were randomly assigned to receive neoadjuvant combination therapy with palbociclib and giredestrant or anastrozole, followed by surgical intervention within 14 days. The tumor biomarker Ki67 of the patients was ≥ 5% when they were enrolled in the group. The analysis showed that patients receiving giredestrant combination therapy (mean Ki67 reduction of 80%) had a greater mean reduction in Ki67 levels from baseline at week 2 compared with anastrozole combination therapy (mean Ki67 reduction of 67%). The pivotal phase 3 trial of giredestrant is recruiting patients and preliminary data is expected in 2025. Chemenu has been working to develop more compounds for drug discovery. Here are the building blocks we can provide.
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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