Imlunestrant

Summary

Imlunestrant (CHEMBL5095183) is a phase-3 clinical-stage small molecule targeting ESR1; indicated across 3 conditions including breast neoplasm and neoplasm.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• Targets: 1 (ESR1)
• Indications: 3 conditions
• Clinical trials: 15
• Chemistry: 524.5 Da · C29H24F4N2O3

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL5095183
Name	Imlunestrant
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	146603228
Molecular formula	C29H24F4N2O3
Molecular weight	524.5
InChIKey	UVBQMXOKKDCBJN-MUUNZHRXSA-N

SMILES: C1C(CN1CCOC2=CC=C(C=C2)[C@@H]3C4=C5C=CC(=CC5=NC=C4C6=C(O3)C=C(C=C6)C(F)(F)F)O)CF

IUPAC name: (5R)-5-[4-[2-[3-(fluoromethyl)azetidin-1-yl]ethoxy]phenyl]-8-(trifluoromethyl)-5H-chromeno[4,3-c]quinolin-2-ol

Also known as: Imlunestrant, Ly 3484356, LY-3484356, LY3484356, IMLUNESTRANT

Patent coverage: 71 distinct patent families (136 SureChEMBL compound mentions), from 4 matched compound structure(s). Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
ESR1	Estrogen receptor-α	Antagonist	9.51	1.7%	P03372

Broader ChEMBL bioactivity targets: 1 (assay-derived). Sample: Estrogen receptor.

Bioactivity

ChEMBL activities: 9 potent at pChembl ≥ 5 of 9 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
ESR1	9.51	Ki	0.31	nM	CHEMBL_ACT_28510946
ESR1	9.19	Ki	0.64	nM	CHEMBL_ACT_25568166
ESR1	8.55	Ki	2.8	nM	CHEMBL_ACT_25568167
ESR1	8.55	Ki	2.79	nM	CHEMBL_ACT_28510949
ESR1	8.52	IC50	3	nM	CHEMBL_ACT_25568168
ESR1	8.02	IC50	9.6	nM	CHEMBL_ACT_25568169
ESR1	7.91	Ki	12.4	nM	CHEMBL_ACT_27966557
ESR1	7.91	Ki	12.4	nM	CHEMBL_ACT_28990169
ESR1	7.24	Ki	57.2	nM	CHEMBL_ACT_27966560

Target pathways

Aggregated over 1 target gene(s): ESR1.

Top Reactome pathways

17 total, by targets touching each:

Pathway	Targets	Genes
Nuclear signaling by ERBB4	1	ESR1
PIP3 activates AKT signaling	1	ESR1
Constitutive Signaling by Aberrant PI3K in Cancer	1	ESR1
Nuclear Receptor transcription pathway	1	ESR1
SUMOylation of intracellular receptors	1	ESR1
Ovarian tumor domain proteases	1	ESR1
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	1	ESR1
TFAP2 (AP-2) family regulates transcription of growth factors and their receptors	1	ESR1
RUNX1 regulates estrogen receptor mediated transcription	1	ESR1
ESR-mediated signaling	1	ESR1
RUNX1 regulates transcription of genes involved in WNT signaling	1	ESR1
Regulation of RUNX2 expression and activity	1	ESR1
Extra-nuclear estrogen signaling	1	ESR1
Estrogen-dependent gene expression	1	ESR1
Mitochondrial unfolded protein response (UPRmt)	1	ESR1
Developmental Lineage of Mammary Gland Luminal Epithelial Cells	1	ESR1
Developmental Lineage of Mammary Gland Alveolar Cells	1	ESR1

Dominant GO biological processes

GO term	Targets
negative regulation of transcription by RNA polymerase II	1
antral ovarian follicle growth	1
epithelial cell development	1
chromatin remodeling	1
regulation of DNA-templated transcription	1
regulation of transcription by RNA polymerase II	1
signal transduction	1
phospholipase C-activating G protein-coupled receptor signaling pathway	1
positive regulation of cytosolic calcium ion concentration	1
androgen metabolic process	1
male gonad development	1
negative regulation of gene expression	1
nuclear receptor-mediated steroid hormone signaling pathway	1
estrogen receptor signaling pathway	1
response to estradiol	1

Indications & clinical

Indications

3 indications (0 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
breast neoplasm	3	MONDO:0021100	MONDO:0007254
neoplasm	2	MONDO:0005070	EFO:0000616

1 further indication record had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 15.

Phase distribution

Phase	Trials
PHASE1	9
PHASE2	3
PHASE3	2
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04975308	PHASE3	ACTIVE_NOT_RECRUITING	A Study of Imlunestrant, Investigator’s Choice of Endocrine Therapy, and Imlunestrant Plus Abemaciclib in Participants With ER+, HER2- Advanced Breast Cancer
NCT05514054	PHASE3	ACTIVE_NOT_RECRUITING	A Study of Imlunestrant Versus Standard Endocrine Therapy in Participants With Early Breast Cancer
NCT05768139	PHASE1/PHASE2	RECRUITING	First-in-Human Study of Tersolisib (STX-478) as Monotherapy and in Combination With Other Antineoplastic Agents in Participants With Advanced Solid Tumors
NCT07191717	PHASE2	NOT_YET_RECRUITING	Imlunestrant and Abemaciclib for the Treatment of Estrogen Receptor Positive Breast Cancer in Patients With Minimal Residual Disease, MIRI Trial
NCT07287098	PHASE2	NOT_YET_RECRUITING	A Study of Imlunestrant (LY3484356) in Premenopausal Women With Estrogen Receptor-Positive (ER+) Human Epidermal Growth Factor Receptor 2 Negative (HER2-) Early Breast Cancer
NCT07410559	PHASE2	NOT_YET_RECRUITING	Neoadjuvant Imlunestrant Plus Abemaciclib Treatment Guided by Ki67 Index After 2 Weeks for ER-Positive HER2-Negative Breast Cancer
NCT04188548	PHASE1	ACTIVE_NOT_RECRUITING	A Study of LY3484356 in Participants With Advanced or Metastatic Breast Cancer or Endometrial Cancer
NCT05307705	PHASE1	ACTIVE_NOT_RECRUITING	A Study of LOXO-783 in Patients With Breast Cancer/Other Solid Tumors
NCT05509790	PHASE1	ACTIVE_NOT_RECRUITING	A Study of LY3484356 in Chinese Participants With Advanced Breast Cancer
NCT04647487	PHASE1	COMPLETED	A Study of LY3484356 in Women With Breast Cancer Before Having Surgery
NCT04840888	PHASE1	COMPLETED	A Study of LY3484356 in Healthy Female Participants
NCT04991766	PHASE1	COMPLETED	A Study of [¹⁴C]-LY3484356 in Healthy Female Participants
NCT05440344	PHASE1	COMPLETED	A Study of Imlunestrant (LY3484356) in Female Participants With Impaired Liver Function
NCT05444556	PHASE1	COMPLETED	A Study of Imlunestrant (LY3484356) in Female Healthy Participants
NCT05509816	PHASE1	COMPLETED	A Study of Imlunestrant (LY3484356) in Healthy Women

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline or drug-level clinical/variant annotations in PharmGKB for this molecule.

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

173 molecules share ≥1 primary target. Top 60 by shared-target count:

Molecule	Source	Status	Shared targets
FULVESTRANT	ChEMBL + PubChem	Phase 4 (approved)	ESR1
ACETOPHENAZINE	ChEMBL	Phase 4 (approved)	ESR1
ALECTINIB	ChEMBL	Phase 4 (approved)	ESR1
APOMORPHINE	ChEMBL	Phase 4 (approved)	ESR1
ARIPIPRAZOLE	ChEMBL	Phase 4 (approved)	ESR1
ASPIRIN	ChEMBL	Phase 4 (approved)	ESR1
AZTREONAM	ChEMBL	Phase 4 (approved)	ESR1
BAZEDOXIFENE	ChEMBL	Phase 4 (approved)	ESR1
BELINOSTAT	ChEMBL	Phase 4 (approved)	ESR1
BENZBROMARONE	ChEMBL	Phase 4 (approved)	ESR1
BEXAROTENE	ChEMBL	Phase 4 (approved)	ESR1
BISACODYL	ChEMBL	Phase 4 (approved)	ESR1
BITHIONOL	ChEMBL	Phase 4 (approved)	ESR1
BROMOCRIPTINE	ChEMBL	Phase 4 (approved)	ESR1
BUTOCONAZOLE	ChEMBL	Phase 4 (approved)	ESR1
CANDESARTAN CILEXETIL	ChEMBL	Phase 4 (approved)	ESR1
CASPOFUNGIN	ChEMBL	Phase 4 (approved)	ESR1
CEFADROXIL	ChEMBL	Phase 4 (approved)	ESR1
CEFEPIME	ChEMBL	Phase 4 (approved)	ESR1
CEFTAZIDIME	ChEMBL	Phase 4 (approved)	ESR1
CERIVASTATIN	ChEMBL	Phase 4 (approved)	ESR1
CHLOROTRIANISENE	ChEMBL	Phase 4 (approved)	ESR1
CISPLATIN	ChEMBL	Phase 4 (approved)	ESR1
CLOFAZIMINE	ChEMBL	Phase 4 (approved)	ESR1
CLOMIPHENE	ChEMBL	Phase 4 (approved)	ESR1
CYCLOFENIL	ChEMBL	Phase 4 (approved)	ESR1
DANAZOL	ChEMBL	Phase 4 (approved)	ESR1
DAUNORUBICIN	ChEMBL	Phase 4 (approved)	ESR1
DEQUALINIUM	ChEMBL	Phase 4 (approved)	ESR1
DESOGESTREL	ChEMBL	Phase 4 (approved)	ESR1
DIENESTROL	ChEMBL	Phase 4 (approved)	ESR1
DIETHYLSTILBESTROL	ChEMBL	Phase 4 (approved)	ESR1
DINOPROSTONE	ChEMBL	Phase 4 (approved)	ESR1
DOXORUBICIN	ChEMBL	Phase 4 (approved)	ESR1
DRONEDARONE	ChEMBL	Phase 4 (approved)	ESR1
ELACESTRANT	ChEMBL	Phase 4 (approved)	ESR1
ERGOCALCIFEROL	ChEMBL	Phase 4 (approved)	ESR1
ERTAPENEM	ChEMBL	Phase 4 (approved)	ESR1
ESTETROL	ChEMBL	Phase 4 (approved)	ESR1
ESTRADIOL	ChEMBL	Phase 4 (approved)	ESR1
ESTRADIOL CYPIONATE	ChEMBL	Phase 4 (approved)	ESR1
ESTRADIOL VALERATE	ChEMBL	Phase 4 (approved)	ESR1
ESTRAMUSTINE	ChEMBL	Phase 4 (approved)	ESR1
ESTRIOL	ChEMBL	Phase 4 (approved)	ESR1
ESTRONE	ChEMBL	Phase 4 (approved)	ESR1
ETHINYL ESTRADIOL	ChEMBL	Phase 4 (approved)	ESR1
ETHYLESTRENOL	ChEMBL	Phase 4 (approved)	ESR1
ETHYNODIOL DIACETATE	ChEMBL	Phase 4 (approved)	ESR1
ETONOGESTREL	ChEMBL	Phase 4 (approved)	ESR1
ETRAVIRINE	ChEMBL	Phase 4 (approved)	ESR1
FLUPIRTINE	ChEMBL	Phase 4 (approved)	ESR1
HEXACHLOROPHENE	ChEMBL	Phase 4 (approved)	ESR1
HEXESTROL	ChEMBL	Phase 4 (approved)	ESR1
IBUPROFEN	ChEMBL	Phase 4 (approved)	ESR1
ISOCONAZOLE	ChEMBL	Phase 4 (approved)	ESR1
LASOFOXIFENE	ChEMBL	Phase 4 (approved)	ESR1
LENVATINIB	ChEMBL	Phase 4 (approved)	ESR1
LEVONORGESTREL	ChEMBL	Phase 4 (approved)	ESR1
LUSUTROMBOPAG	ChEMBL	Phase 4 (approved)	ESR1
LYMECYCLINE	ChEMBL	Phase 4 (approved)	ESR1