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Imlunestrant
This information is provided in response to your request. Resources may contain information about doses, uses, formulations and populations different from product labeling.
What is the mechanism of action of imlunestrant?
LY3484356 (imlunestrant) is a novel, orally bioavailable selective estrogen receptor degrader (SERD) with pure antagonistic properties resulting in sustained inhibition of ER-dependent gene transcription and cell growth.
Mechanism of Action (MOA)
Imlunestrant is an investigational next generation orally bioavailable selective estrogen receptor degrader and estrogen receptor alpha (ERα) pure antagonist with activity against the wild type and mutant ERα.1,2 As the mutation can lead to estrogen-independent receptor activity, targeting and inhibiting the activity of this mutant receptor is critical.3,4
Estrogen receptor signaling plays an important role in organ development and growth. In certain cancers, abnormal estrogen receptor signaling is a key component of tumor growth (see Imlunestrant Pathway Target).5 Disruption of estrogen receptor signaling by selective estrogen receptor degraders is one of the treatment options for patients with estrogen receptor-positive cancers.3,6
Figure 1 description: The estrogen signaling pathway in a breast cancer cell is illustrated and is the target for the imlunestrant molecule. Imlunestrant has demonstrated the inhibition of estrogen-dependent signaling and subsequent inhibition of cell proliferation in estrogen receptor-expressing tumor models.1
Abbreviation: ER = estrogen receptor.
Additional information on the MOA of imlunestrant is available in the imlunestrant MOA video.
References
The published references below are available by contacting 1-800-LillyRx (1-800-545-5979).
1Bhagwat 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
2Vandekopple 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
3Patel HK, Bihani T. Selective estrogen receptor modulators (SERMs) and selective estrogen receptor degraders (SERDs) in cancer treatment. Pharmacol Ther. 2018;186:1-24. https://doi.org/10.1016/j.pharmthera.2017.12.012
4Jeselsohn R, Yelensky R, Buchwalter G, et al. Emergence of constitutively active estrogen receptor-α mutations in pretreated advanced estrogen receptor-positive breast cancer. Clin Cancer Res. 2014;20(7):1757-1767. https://doi.org/10.1158/1078-0432.ccr-13-2332
5Lee HR, Hwang KA, Park MA, et al. Treatment with bisphenol A and methoxychlor results in the growth of human breast cancer cells and alteration of the expression of cell cycle-related genes, cyclin D1 and p21, via an estrogen receptor-dependent signaling pathway. Int J Mol Med. 2012;29(5):883-890. https://doi.org/10.3892/ijmm.2012.903
6Wardell SE, Ellis MJ, Alley HM, et al. Efficacy of SERD/SERM hybrid-CDK4/6 inhibitor combinations in models of endocrine therapy-resistant breast cancer. Clin Cancer Res. 2015;21(22):5121-5130. https://doi.org/10.1158/1078-0432.CCR-15-0360
7Gladden AB, Diehl JA. Location, location, location: the role of cyclin D1 nuclear localization in cancer. J Cell Biochem. 2005;96(5):906-913. https://doi.org/10.1002/jcb.20613
8Tecalco-Cruz AC, Pérez-Alvarado IA, Ramírez-Jarquín JO, Rocha-Zavaleta L. Nucleo-cytoplasmic transport of estrogen receptor alpha in breast cancer cells. Cell Signal. 2017;34:121-132. https://doi.org/10.1016/j.cellsig.2017.03.011
Date of Last Review: August 17, 2023