Amcenestrant
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Also known as SAR-439859Sar439859
Summary
Amcenestrant (CHEMBL4475463) is a phase-3 clinical-stage small molecule targeting ESR1; indicated across 3 conditions including breast neoplasm and angiosarcoma.
At a glance
- Status: Max clinical phase 3 (not approved)
- Modality: Small molecule
- Targets: 1 (ESR1)
- Indications: 3 conditions
- Clinical trials: 9
- Chemistry: 554.5 Da · C31H30Cl2FNO3
Identifiers
Drug identity and classification
| Field | Value |
|---|---|
| ChEMBL ID | CHEMBL4475463 |
| Name | Amcenestrant |
| Type | Small molecule |
| Max phase | 3 |
| FDA approved | no |
| PubChem CID | 130232326 |
| Molecular formula | C31H30Cl2FNO3 |
| Molecular weight | 554.5 |
| InChIKey | KISZAGQTIXIVAR-VWLOTQADSA-N |
SMILES: C1CC2=C(C=CC(=C2)C(=O)O)C(=C(C1)C3=C(C=C(C=C3)Cl)Cl)C4=CC=C(C=C4)O[C@H]5CCN(C5)CCCF
IUPAC name: 6-(2,4-dichlorophenyl)-5-[4-[(3S)-1-(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-8,9-dihydro-7H-benzo[7]annulene-2-carboxylic acid
Also known as: Amcenestrant, SAR-439859, Sar439859, SAR439859, AMCENESTRANT
Patent coverage: 211 distinct patent families (531 SureChEMBL compound mentions), from 3 matched compound structure(s). One matched structure accounts for 416 (78%) of the total. 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 | 1.7% | P03372 |
Broader ChEMBL bioactivity targets: 2 (assay-derived). Sample: Estrogen receptor, Estrogen receptor beta.
Bioactivity
ChEMBL activities: 12 potent at pChembl ≥ 5 of 12 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):
| Target | pChembl | Type | Value | Unit | Activity ID |
|---|---|---|---|---|---|
| ESR1 | 9.7 | EC50 | 0.2 | nM | CHEMBL_ACT_18924888 |
| ESR1 | 9.4 | EC50 | 0.4 | nM | CHEMBL_ACT_25568143 |
| ESR1 | 8.92 | EC50 | 1.2 | nM | CHEMBL_ACT_24910832 |
| ESR1 | 8.74 | IC50 | 1.8 | nM | CHEMBL_ACT_25568139 |
| ESR1 | 8.7 | IC50 | 2 | nM | CHEMBL_ACT_29106417 |
| ESR2 | 8.08 | IC50 | 8.4 | nM | CHEMBL_ACT_25568141 |
| ESR2 | 8.07 | IC50 | 8.6 | nM | CHEMBL_ACT_24910968 |
| ESR1 | 7.82 | IC50 | 15 | nM | CHEMBL_ACT_26807467 |
| ESR1 | 7.76 | IC50 | 17.2 | nM | CHEMBL_ACT_24911036 |
| ESR1 | 7.24 | IC50 | 57.7 | nM | CHEMBL_ACT_24911033 |
| ESR1 | 6.66 | IC50 | 221 | nM | CHEMBL_ACT_26807473 |
| ESR1 | 6.41 | IC50 | 389 | nM | CHEMBL_ACT_26807470 |
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 |
| angiosarcoma | 2 | MONDO:0016982 | EFO:0003968 |
1 further indication record had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.
Clinical trials
Total trials: 9.
Phase distribution
| Phase | Trials |
|---|---|
| PHASE2 | 3 |
| PHASE1 | 3 |
| PHASE3 | 2 |
| PHASE1/PHASE2 | 1 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT04478266 | PHASE3 | TERMINATED | Amcenestrant (SAR439859) Plus Palbociclib as First Line Therapy for Patients With ER (+) HER2(-) Advanced Breast Cancer |
| NCT05128773 | PHASE3 | TERMINATED | Study of Amcenestrant (SAR439859) Versus Tamoxifen for Patients With Hormone Receptor-positive (HR+) Early Breast Cancer, Who Have Discontinued Adjuvant Aromatase Inhibitor Therapy Due to Treatment-related Toxicity |
| NCT01042379 | PHASE2 | RECRUITING | I-SPY TRIAL: Neoadjuvant and Personalized Adaptive Novel Agents to Treat Breast Cancer |
| NCT03284957 | PHASE1/PHASE2 | TERMINATED | Phase 1/2 Study of Amcenestrant (SAR439859) Single Agent and in Combination With Other Anti-cancer Therapies in Postmenopausal Women With Estrogen Receptor Positive Advanced Breast Cancer |
| NCT04059484 | PHASE2 | TERMINATED | Phase 2 Study of Amcenestrant (SAR439859) Versus Physician’s Choice in Locally Advanced or Metastatic ER-positive Breast Cancer |
| NCT04191382 | PHASE2 | TERMINATED | Phase 2 Window Study of SAR439859 (Amcenestrant) Versus Letrozole in Post-menopausal Patients With ER+, HER2- Pre-operative Post-menopausal Primary Breast Cancer |
| NCT03816839 | PHASE1 | TERMINATED | Evaluation of Orally Administered Amcenestrant (SAR439859) in Japanese Postmenopausal Patients With Advanced Breast Cancer (AMEERA-2) |
| NCT04940026 | PHASE1 | COMPLETED | Study to Determine Absorption, Metabolism, and Excretion of [14C]-SAR439859, and to Assess Absolute Oral Bioavailability of Amcenestrant (SAR439859), in Healthy Post-menopausal Women |
| NCT05126329 | PHASE1 | TERMINATED | Pharmacokinetics of Amcenestrant in Female Hepatic Impaired Participants as Compared to Participants With Normal Hepatic Function |
Clinical evidence (CIViC)
No CIViC predictive evidence (expected for non-precision-medicine drugs).
Pharmacology
Pharmacogenomics
No PharmGKB pharmacogenomic data curated for this drug.
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 |
Related Atlas pages
- Genes: ESR1
- Diseases: breast neoplasm
- Drugs: Fulvestrant, Acetophenazine, Alectinib, Apomorphine, Aripiprazole, Aspirin, Aztreonam, Bazedoxifene, Belinostat, Benzbromarone, Bexarotene, Bisacodyl, Bithionol, Bromocriptine, Butoconazole, Candesartan Cilexetil, Caspofungin, Cefadroxil, Cefepime, Ceftazidime, Cerivastatin, Chlorotrianisene, Cisplatin, Clofazimine, Clomiphene, Cyclofenil, Danazol, Daunorubicin, Dequalinium, Desogestrel, Dienestrol, Diethylstilbestrol, Dinoprostone, Doxorubicin, Dronedarone, Elacestrant, Ergocalciferol, Ertapenem, Estetrol, Estradiol, Estradiol Cypionate, Estradiol Valerate, Estramustine, Estriol, Estrone, Ethinyl Estradiol, Ethylestrenol, Ethynodiol Diacetate, Etonogestrel, Etravirine, Flupirtine, Hexachlorophene, Hexestrol, Ibuprofen, Isoconazole, Lasofoxifene, Lenvatinib, Levonorgestrel, Lusutrombopag, Lymecycline