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Imlunestrant
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Does imlunestrant cross the blood brain barrier?
Imlunestrant is an oral brain-penetrant selective estrogen receptor degrader (SERD) that has demonstrated activity in a preclinical brain metastasis model.
Imlunestrant Brain Penetration and Activity in Brain Metastasis: Preclinical Data
LY3484356 (imlunestrant) is a novel, orally bioavailable selective estrogen receptor degrader (SERD) with pure antagonistic properties resulting in sustained inhibition of estrogen receptor (ER)-dependent gene transcription and cell growth.1,2
Imlunestrant showed sustained exposure in the brains of mice, demonstrating its ability to effectively cross the blood-brain barrier (see Imlunestrant Brain Exposure in Preclinical Analyses). In an ER+ brain orthotopic mouse model, imlunestrant treatment prolonged overall survival compared to control, fulvestrant, and alternative SERD therapies (see Imlunestrant CNS Activity and Overall Survival in a Brain Orthotopic Model).3
Figure 1 description: In pharmacokinetic/pharmacodynamic analyses of mice bearing MCF7 xenografts, imlunestrant demonstrated dose dependent exposure in the brain, prolonged brain exposure, sustained progesterone receptor gene expression inhibition, and reduction of estrogen receptor alpha and progesterone receptor by immunohistochemistry (not shown).
Abbreviations: PGR = progesterone receptor; PK = pharmacokinetics; PO = by mouth; QD = daily; SEM = standard error of the mean.
Figure 2 description: Imlunestrant demonstrated central nervous system penetrance and improved survival probability in an estrogen receptor-positive brain orthotopic model.
Abbreviation: CNS = central nervous system.
References
The published references below are available by contacting 1-800-LillyRx (1-800-545-5979).
1Vandekopple M, Mur C, Shen W, et al. Preclinical characterization of imlunestrant, an oral brain-penetrant selective estrogen receptor degrader with activity in a brain metastasis (BM) model. ESMO Open. 2023;8(1 suppl 4):101265. European Society for Medical Oncology abstract 41P. https://doi.org/10.1016/j.esmoop.2023.101265
2Bhagwat SV, Zhao B, Shen W, et al. Preclinical characterization of LY3484356, a novel, potent and orally bioavailable selective estrogen receptor degrader (SERD). Cancer Res. 2021;18(13 suppl):1236. American Association of Cancer Research abstract 1236. https://doi.org/10.1158/1538-7445.AM2021-1236
3Vandekopple M, Mur C, Shen W, et al. Preclinical characterization of imlunestrant, an oral brain-penetrant selective estrogen receptor degrader with activity in a brain metastasis (BM) model. Poster presented at: 5th European Society for Medical Oncology Breast Cancer (ESMO-BC) Congress; May 11-13, 2023; Berlin, Germany. Accessed October 11, 2023. https://cslide.ctimeetingtech.com/breast23hybrid/public/download_uploaded_media/pdf/125
Date of Last Review: September 29, 2023