Giredestrant is an investigational oral selective estrogen receptor degrader (SERD) being developed for the treatment of estrogen receptor-positive (ER+) breast cancer.[1][2] It is a potent, nonsteroidal compound that antagonizes estrogen effects by competitively binding to both wild-type and mutant estrogen receptors with nanomolar potency.[1][3] Giredestrant works by inducing an inactive conformation of the estrogen receptor ligand-binding domain and promoting proteasome-mediated degradation of the receptor protein.[1][4][5]
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| Formula | C27H31F5N4O |
| Molar mass | 522.564 g·mol−1 |
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Research
editIn clinical trials, giredestrant has been evaluated in patients with ER+ breast cancer, including those with ESR1 mutations, both as a single agent and in combination with other therapies.[2][6] Its orally bioavailable.[3][4]
References
edit- ^ a b c "Giredestrant (GDC-9545)". NCI Formulatry. U.S. National Cancer Institute.
- ^ a b Malhi V, Agarwal P, Gates MR, Liu L, Wang J, De Bruyn T, et al. (December 2023). "Optimizing Early-stage Clinical Pharmacology Evaluation to Accelerate Clinical Development of Giredestrant in Advanced Breast Cancer". Cancer Research Communications. 3 (12): 2551–2559. doi:10.1158/2767-9764.CRC-23-0324. PMC 10722959. PMID 38019116.
- ^ a b "A clinical study to compare giredestrant with fulvestrant, both combined with a targeted therapy (CDK4/6 inhibitor) in people with ER‑positive, HER2-negative breast cancer that has come back after adjuvant hormone therapy". Roche.
- ^ a b Jhaveri KL, Bellet M, Turner NC, Loi S, Bardia A, Boni V, et al. (February 2024). "Phase Ia/b Study of Giredestrant ± Palbociclib and ± Luteinizing Hormone-Releasing Hormone Agonists in Estrogen Receptor-Positive, HER2-Negative, Locally Advanced/Metastatic Breast Cancer". Clinical Cancer Research. 30 (4): 754–766. doi:10.1158/1078-0432.CCR-23-1796. PMC 10870118. PMID 37921755.
- ^ Liang J, Zbieg JR, Blake RA, Chang JH, Daly S, DiPasquale AG, et al. (August 2021). "GDC-9545 (Giredestrant): A Potent and Orally Bioavailable Selective Estrogen Receptor Antagonist and Degrader with an Exceptional Preclinical Profile for ER+ Breast Cancer". Journal of Medicinal Chemistry. 64 (16): 11841–11856. doi:10.1021/acs.jmedchem.1c00847. PMID 34251202.
- ^ Lawrence L (25 July 2024). "Giredestrant Bests Anastrozole in ER+, HER2- Early Breast Cancer".
Further reading
edit- Gheysen M, Punie K, Wildiers H, Neven P (November 2024). "Oral SERDs changing the scenery in hormone receptor positive breast cancer, a comprehensive review". Cancer Treatment Reviews. 130: 102825. doi:10.1016/j.ctrv.2024.102825. PMID 39293125.
- Guglielmi G, Del Re M, Gol LS, Bengala C, Danesi R, Fogli S (April 2024). "Pharmacological insights on novel oral selective estrogen receptor degraders in breast cancer". European Journal of Pharmacology. 969: 176424. doi:10.1016/j.ejphar.2024.176424. PMID 38402929.
- Garcia-Fructuoso I, Gomez-Bravo R, Schettini F (November 2022). "Integrating new oral selective oestrogen receptor degraders in the breast cancer treatment". Current Opinion in Oncology. 34 (6): 635–642. doi:10.1097/CCO.0000000000000892. PMID 36000362.
- Chen YC, Yu J, Metcalfe C, De Bruyn T, Gelzleichter T, Malhi V, et al. (June 2022). "Latest generation estrogen receptor degraders for the treatment of hormone receptor-positive breast cancer". Expert Opinion on Investigational Drugs. 31 (6): 515–529. doi:10.1080/13543784.2021.1983542. PMID 34694932.
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