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  1. Medical Information Right
  2. Investigational Drugs Right
  3. Imlunestrant Right
  4. What is the mechanism of action of imlunestrant?
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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?

Imlunestrant is a potent, orally bioavailable selective estrogen receptor degrader with pure antagonistic properties resulting in sustained inhibition of estrogen receptor-dependent gene transcription and cell growth.

US_cFAQ_IML001_MOA
US_cFAQ_IML001_MOAen-US

Mechanism of Action (MOA)

Imlunestrant is a potent degrader and selective pure antagonist of wild-type and mutant estrogen receptor alpha (ERα). In cell proliferation assays, it selectively inhibits the proliferation of estrogen receptor-positive (ER+) breast cancer cell lines and has equivalent potency in both wild-type and mutant estrogen receptor gene (ESR1) cell lines. In the in-vivo target inhibition studies, imlunestrant has shown sustained and prolonged inhibition of expression of progesterone receptor (PgR), a transcriptional target of ERα and a pharmacodynamic biomarker in ESR1 wild-type and ESR1 (Y537S)-mutant xenograft or patient-derived xenograft (PDX) tumor models in mice. In in vivo efficacy studies, imlunestrant has demonstrated robust single agent activity and tumor regressions in ESR1 wild-type (MCF7, T47D, ZR-75-1, HCC1428) xenograft models and ESR1-mutant (Y537S, E380Q) PDX models. In preclinical combination efficacy studies, imlunestrant has shown good tolerability and enhanced efficacy with abemaciclib, alpelisib, and everolimus.1-4

Imlunestrant ER Pathway1,3,5-7

Figure 1 description: The selective estrogen receptor degradation mechanism of action of imlunestrant is illustrated. Imlunestrant has demonstrated inhibition of estrogen-dependent signaling and subsequent inhibition of cell proliferation in estrogen receptor wild-type and mutant expressing tumor models.

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;81(13 suppl):1236. American Association for Cancer Research abstract 1236. https://doi.org/10.1158/1538-7445.AM2021-1236

2Bhagwat SV, Zhao B, Shen W, et al. Preclinical characterization of LY3484356, a novel, potent and orally bioavailable selective estrogen receptor degrader (SERD). Poster presented at: 112th Annual Meeting of the American Association for Cancer Research (AACR Virtual); April 10-15, May 17-21, 2021. 

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. ESMO Open. 2023;8(1 suppl 4):101265. European Society for Medical Oncology abstract 41P. https://doi.org/10.1016/j.esmoop.2023.101265

4Vandekopple 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

5Patel 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

6Jeselsohn 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

7Tecalco-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: October 02, 2024

Additional related information:

  • Preclinical Characterization of Imlunestrant, an Oral Brain-Penetrant Selective Estrogen Receptor Degrader with Activity in a Brain Metastasis (BM) Model
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