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On September 25, 2025, the Food and Drug Administration approved imlunestrant (Inluriyo, Eli Lilly and Company), an estrogen receptor antagonist, for adults with estrogen receptor (ER)-positive, human epidermal growth factor 2 (HER2)-negative, estrogen receptor-1 (ESR1)-mutated advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy. FDA also approved the Guardant360 CDx assay as a companion diagnostic device to identify patients with breast cancer with ESR1 mutations for treatment with imlunestrant.
Physicochemical Properties
| Molecular Formula | C29H24F4N2O3 |
| Molecular Weight | 524.506081581116 |
| Exact Mass | 524.172 |
| Elemental Analysis | C, 66.41; H, 4.61; F, 14.49; N, 5.34; O, 9.15 |
| CAS # | 2408840-26-4 |
| Related CAS # | Imlunestrant tosylate;2408840-41-3;(S)-Imlunestrant tosylate;2408840-43-5 |
| PubChem CID | 146603228 |
| Appearance | Light yellow to yellow solid powder |
| LogP | 6 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 9 |
| Rotatable Bond Count | 6 |
| Heavy Atom Count | 38 |
| Complexity | 788 |
| Defined Atom Stereocenter Count | 1 |
| SMILES | FCC1CN(CCOC2C=CC(=CC=2)[C@@H]2C3C4C=CC(=CC=4N=CC=3C3C=CC(C(F)(F)F)=CC=3O2)O)C1 |
| InChi Key | UVBQMXOKKDCBJN-MUUNZHRXSA-N |
| InChi Code | InChI=1S/C29H24F4N2O3/c30-13-17-15-35(16-17)9-10-37-21-5-1-18(2-6-21)28-27-23-8-4-20(36)12-25(23)34-14-24(27)22-7-3-19(29(31,32)33)11-26(22)38-28/h1-8,11-12,14,17,28,36H,9-10,13,15-16H2/t28-/m1/s1 |
| Chemical Name | (5R)-5-[4-[2-[3-(fluoromethyl)azetidin-1-yl]ethoxy]phenyl]-8-(trifluoromethyl)-5H-chromeno[4,3-c]quinolin-2-ol |
| Synonyms | Imlunestrant; 2408840-26-4; LY3484356; 9CXQ3PF69U; LY-3484356; . |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets | ER/estrogen receptor; selective estrogen receptor degrader (SERD) |
| ln Vitro |
In ESR1 mutants, LY3484356 exhibits favorable pharmacokinetic (PK) characteristics, including antitumor activity [1]. Estrogen receptor signalling has closely been tied to breast cancer progression and cancer cell proliferation. Estrogen receptor alpha (ERα) has been primarily implicated in breast cancer, and its activation promotes the expression of oncogenic factors that increase cancer cell proliferation, such as MYC, Cyclin D1, FOXM1, GREB1, BCL2 or amphiregulin, IGF-1 and CXCL12. Imlunestrant binds to ERα with high affinity and, in vitro, induces degradation of ERα: This leads to the inhibition of ER-dependent gene transcription and cellular proliferation in ER+ breast cancer cells. Imlunestrant is an estrogen receptor (ER) antagonist that induces degradation of ERα, leading to inhibition of ER-dependent gene transcription and cellular proliferation in ER+ breast cancer cells. Imlunestrant exposure-response relationships and the time course of pharmacodynamics have not been fully characterized. |
| ln Vivo | Imlunestrant demonstrated in vivo antitumour activity in ER+ breast cancer xenograft models, including models with ESR1 mutations. Imlunestrant is an orally available selective estrogen receptor degrader (SERD), with potential antineoplastic activity. Upon oral administration, imlunestrant specifically targets and binds to the estrogen receptor (ER) and induces a conformational change that results in ER degradation. This prevents ER-mediated signaling and inhibits both the growth and survival of ER-expressing cancer cells. Imlunestrant is able to cross the blood-brain barrier (BBB). IMLUNESTRANT is a small molecule drug with a maximum clinical trial phase of III (across all indications) and has 3 investigational indications. |
| ADME/Pharmacokinetics |
Absorption The mean (%CV) maximum concentration (Cmax) of imlunestrant is 141 ng/mL (45%) and the area under the concentration-time curve (AUC) is 2,400 ng x h/mL (46%). Imlunestrant Cmax and AUC increase in a dose proportional manner over a dosage range of 200 mg to 1,200 mg (0.5 to 3 times the approved recommended dosage) once daily. Steady-state is reached in approximately six days and the accumulation is 2.3-fold based on AUC. Imlunestrant absolute oral bioavailability after a single oral 400 mg dose is 10% (32%). Imlunestrant median (min, max) time to maximum plasma concentration (Tmax) is 4 (2, 8) hours. Imlunestrant AUC increased 2-fold and Cmax increased 3.6-fold following administration with a low-fat meal (approximately 475 calories with 13% fat, 16% protein, and 71% carbohydrates). The effect of high-fat meal (approximately 800-1,000 calories with 500-600 calories from fat) on imlunestrant exposures is unknown. Route of Elimination After a single dose of radiolabeled imlunestrant 400 mg to healthy subjects, 97% of the dose was recovered in feces (62% unchanged) and 0.3% in urine. Volume of Distribution The apparent (oral) volume of distribution is 8,120 L (69%). Clearance An estimated apparent clearance is 166 L/h (51%). Protein Binding Imlunestrant protein binding is >99% and is not concentration-dependent. Metabolism / Metabolites Imlunestrant is metabolized by CYP3A4-mediated sulfation and direct glucuronidation catalyzed by UGT1A1, 1A3, 1A8, 1A9, 1A10. In a drug metabolism and disposition study, the main metabolite accounting for the highest plasma radioactivity was M1. Other metabolites with relatively identifiable radioactivity include M2 and M12. Biological Half-Life Imlunestrant elimination half-life is 30 hours. |
| Toxicity/Toxicokinetics | Efficacy was evaluated in EMBER-3 (NCT04975308), a randomized, open-label, active-controlled, multicenter trial that enrolled 874 patients with ER-positive, HER2-negative locally advanced or metastatic breast cancer previously treated with an aromatase inhibitor either alone or in combination with a CDK4/6 inhibitor. Patients were excluded if they were eligible to receive a PARP inhibitor. Patients were randomized 1:1:1 to imlunestrant, an investigator’s choice of endocrine therapy (fulvestrant or exemestane), or an additional investigational combination regimen. Randomization was stratified by previous treatment with a CDK4/6 inhibitor, presence of visceral metastasis, and geographic region. ESR1 mutational status was determined by blood circulating tumor deoxyribonucleic acid (ctDNA) analysis using the Guardant360 CDx assay and was limited to specific ESR1 mutations in the ligand-binding domain. The major efficacy outcome was investigator-assessed progression-free survival (PFS) (RECIST v1.1) comparing imlunestrant to the investigator’s choice of endocrine therapy in patients with ESR1 mutated tumors. Other efficacy outcome measures included overall survival (OS) and objective response rate (ORR). In the ESR1 mutated population (n=256), a statistically significant difference in investigator-assessed PFS for imlunestrant compared to investigator’s choice of endocrine therapy was observed. The median PFS was 5.5 months (95% CI: 3.9, 7.4) in the imlunestrant arm and 3.8 months (95% CI: 3.7, 5.5) in the investigator's choice arm (hazard ratio 0.62 [95% CI: 0.46, 0.82]; p-value 0.0008). The ORR was 14.3% in the imlunestrant arm and 7.7% in the investigator's choice arm. At the time of the PFS analysis, OS data was immature with 31% of deaths in the ESR1 mutated population. The most common adverse events (≥10%), including laboratory abnormalities were decreased hemoglobin, musculoskeletal pain, decreased calcium, decreased neutrophils, increased AST, fatigue, diarrhea, increased ALT, increased triglycerides, nausea, decreased platelets, constipation, increased cholesterol, and abdominal pain. |
| References |
[1]. A first-in-human phase 1a/b trial of LY3484356, an oral selective estrogen receptor (ER) degrader (SERD) in ER+ advanced breast cancer (aBC) and endometrial endometrioid cancer (EEC): Results from the EMBER study. 2021 ASCO Annual Meeting I. [2]. Oral Selective Estrogen Receptor Degraders (SERDs) as a Novel Breast Cancer Therapy: Present and Future from a Clinical Perspective. Int. J. Mol. Sci. 2021, 22(15), 7812. |
| Additional Infomation |
Imlunestrant is a brain-penetrant selective estrogen receptor antagonist and degrader. The FDA approved imlunestrant on September 25, 2025 as a treatment for estrogen receptor (ER)-positive, HER2-negative, estrogen receptor 1 (ESR1)-mutated advanced or metastatic breast cancer with progression on at least one line of endocrine therapy. Imlunestrant works by antagonizing ER transcriptional activity and, by forming an unstable drug-receptor complex, promotes ER degradation via the ubiquitin-proteasome pathway. In clinical trials, imlunestrant has been investigated as monotherapy and in combination with other drugs in breast cancer patients.
Imlunestrant is an Estrogen Receptor Antagonist. The mechanism of action of imlunestrant is as an Estrogen Receptor Antagonist, and P-Glycoprotein Inhibitor, and Breast Cancer Resistance Protein Inhibitor.
Background: Novel degraders and antagonists of ER are under evaluation in aBC, to overcome both ER mediated resistance and the bioavailability and dosing limitations of fulvestrant, the only approved SERD. ER is also overexpressed in ̃80% of EEC and endocrine therapy (ET) is utilized for these patients (pts). LY3484356, a novel, orally bioavailable SERD with pure antagonistic properties results in sustained inhibition of ER-dependent gene transcription and cell growth. Preclinically, LY3484356 shows favorable efficacy and pharmacokinetic (PK) properties, including antitumor activity in ESR1 mutants. Here we present the initial clinical data from EMBER, an ongoing first-in-human phase 1a/b trial of this novel agent. Methods: Phase 1a evaluated LY3484356 dose escalation (i3+3 design) in women with ER+, HER2- aBC (≤3 prior therapies for aBC following protocol amendment; prior ET sensitivity) and ER+ EEC (prior platinum therapy). Premenopausal women received a concomitant GnRH agonist. Key endpoints included determination of the recommended phase 2 dose, safety and tolerability, PK, and objective response rate and clinical benefit rate per RECIST v1.1. Results: As of the data cut (November 9, 2020), 28 pts (n = 24 aBC, n = 4 EEC) were enrolled at doses ranging from 200-1200 mg QD. Median age was 59 years (range, 35-80). Median number of prior therapies for aBC was 2 (range, 1-8; 6 pts enrolled prior to protocol amendment had received ≥4 prior therapies), including prior fulvestrant (46%), a CDK4/6 inhibitor (83%), and chemotherapy (33%). No dose-limiting toxicities were observed. Treatment-emergent adverse events (TEAEs) were mostly grade 1-2, including nausea (32%), fatigue (25%), and diarrhea (18%). The only grade 3 treatment-related AE was diarrhea (n = 1). TEAEs of bradycardia and QTc prolongation were not observed despite intensive central ECG monitoring. Dose-proportional increases in LY3484356 exposures were observed across all evaluated doses and t1/2 was 25-30 hours. At the starting dose level (200 mg QD), unbound LY3484356 exposures exceeded those achieved with fulvestrant. 16 of 28 pts were efficacy evaluable, with the remaining 12 pts ongoing prior to first scan. Among 16 evaluable pts, 11 (8 aBC, 3 EEC) had stable disease (10 pts ongoing), and 5 had progressive disease. RECIST responses were observed after the data cut and will be detailed at the meeting. Plasma ctDNA analysis indicated decreases in mutant allele frequencies, including mutant ESR1 in 9/12 (75%) evaluable pts across all dose levels. Conclusions: LY3484356 QD dosing shows favorable safety and PK properties, along with preliminary efficacy in pts with heavily pretreated ER+ aBC and EEC. Updated data will be presented at the meeting. Clinical trial information: NCT04188548. |
Solubility Data
| Solubility (In Vitro) | DMSO: 250 mg/mL (476.64 mM) |
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9065 mL | 9.5327 mL | 19.0654 mL | |
| 5 mM | 0.3813 mL | 1.9065 mL | 3.8131 mL | |
| 10 mM | 0.1907 mL | 0.9533 mL | 1.9065 mL |