Elacestrant

Identification

Summary

Elacestrant is an estrogen receptor antagonist used to treat ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy.

Brand Names

Orserdu

Generic Name

Elacestrant

DrugBank Accession Number

DB06374

Background

Elacestrant is a non-steroidal small molecule and an estrogen receptor (ER) antagonist.^3,8 In January 2023, it was approved by the FDA for the treatment of ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer.^8,9 It received a similar approval in the EU in September 2023.¹¹

Elacestrant binds to estrogen receptor-alpha (ERα) and acts as a selective estrogen receptor degrader (SERD) thanks to its ability to block the transcriptional activity of the ER and promote its degradation.^1,6,9 Other types of endocrine therapy, such as selective estrogen receptor modulators (SERMs) and aromatase inhibitors (AIs), may lead to drug resistance over time; therefore, the use of a SERD represents a therapeutic approach for the treatment of endocrine-resistant breast cancers.⁷ Unlike fulvestrant, another FDA-approved SERD, elacestrant is orally bioavailable.²

Type

Small Molecule

Groups

Approved, Investigational

Structure

3D

Download

MOLSDF3D-SDFPDBSMILESInChI

Similar Structures

Structure for Elacestrant (DB06374)

×

Close

Weight

Average: 458.646
Monoisotopic: 458.293328472

Chemical Formula

C₃₀H₃₈N₂O₂

Synonyms

• (2R)-2-(2-(ethyl-((4-(2-(ethylamino)ethyl)phenyl)methyl)amino)-4-methoxy-phenyl)tetralin-6-ol
• (6R)-6-(2-(ethyl((4-(2- (ethylamino)ethyl)phenyl)methyl)amino)-4-methoxyphenyl)- 5,6,7,8-tetrahydronaphthalen-2-ol
• 2-naphthalenol, 6-(2-(ethyl((4-(2-(ethylamino)ethyl)phenyl)methyl)amino)-4-methoxyphenyl)-5,6,7,8-tetrahydro-, (6R)-
• Elacestrant

External IDs

• ER-306323
• RAD-1901
• RAD1901

Poor quality drug data slowing you down?

Unlock 38% more drug discovery time and eliminate decision-making doubts with this one-stop guide to quality drug data.

Download eBook

Poor quality drug data slowing you down?

Download eBook

Pharmacology

Indication

Elacestrant is indicated for the treatment of postmenopausal women or adult men with ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy.⁸ Elacestrant is indicated for the same in the EU, with an additional requirement that patients trial a CDK 4/6 inhibitor as a prior line of therapy.¹⁰

Reduce drug development failure rates

Build, train, & validate machine-learning models
with evidence-based and structured datasets.

See how

Build, train, & validate predictive machine-learning models with structured datasets.

See how

Associated Conditions

Indication Type	Indication	Combined Product Details	Approval Level	Age Group	Patient Characteristics	Dose Form
Treatment of	Advanced breast cancer		••••••••••••	••••••••••••••	•••• •••• ••••••••• ••••• ••••••••• •••••••	••••••
Treatment of	Advanced breast cancer		••••••••••••	•••••	••••• ••••••••• •••••••• •••• •••• ••••••••	••••••
Treatment of	Locally advanced breast cancer (labc)		••••••••••••	•••••	••••••• ••••••••••• ••••••••• ••• ••• ••••••••• •••••••• •••• •••• ••••••••	••••••
Treatment of	Locally advanced breast cancer (labc)		••••••••••••	••••••••••••••	•••• •••• ••••••••• ••••••• ••••••••••• ••••••••• ••• ••• ••••••••• •••••••	••••••
Treatment of	Metastatic breast cancer		••••••••••••	•••••	•••• •••• ••••••••• ••••••• ••••••••••• ••••••••• ••• ••• ••••••••• •••••••	••••••

Create Account

Contraindications & Blackbox Warnings

Prevent Adverse Drug Events Today

Tap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.

Learn more

Avoid life-threatening adverse drug events with our Clinical API

Learn more

Pharmacodynamics

The exposure-response relationships and pharmacodynamics time course of elacestrant have not been fully characterized. At the approved recommended dose, the use of elacestrant does not lead to QTc interval increases higher than 20 msec. Hypercholesterolemia and hypertriglyceridemia have occurred in patients taking elacestrant, and administering this drug to pregnant women may cause fetal harm.⁸ Unlike other selective estrogen receptor modulators and degraders, elacestrant is capable of crossing the blood-brain barrier.⁶

Mechanism of action

Elacestrant is an oral selective estrogen receptor degrader (SERD) that binds to estrogen receptor-alpha (ERα).^2,3,8 Breast tumors that express ERα depend on estrogen-mediated growth signaling; therefore, endocrine therapies that target the estrogen receptor (ER) are commonly used in the treatment of this type of cancer. SERDs are a type of endocrine therapy that antagonizes the transcriptional activity of the ER and promotes its degradation.¹

In ER-positive (ER+) HER2-negative (HER2-) breast cancer cells, elacestrant inhibits 17β-estradiol-mediated cell proliferation and induces ERα degradation through the proteasomal pathway.⁸ Elacestrant also slows ER nuclear translocation and promotes ER turnover, disrupting downstream signaling.¹ Elacestrant has in vitro and in vivo anti-tumor activity in ER+ HER2- breast cancer models resistant to fulvestrant and cyclin-dependent kinase 4/6 inhibitors, as well as cancer models with estrogen receptor 1 gene (ESR1) mutations.^4,5,8

Target	Actions	Organism
UEstrogen receptor alpha	antagonist	Humans

Absorption

With the recommended dosage of 345 mg once daily, elacestrant has a steady-state C_max of 119 ng/mL and an AUC_0-24h of 2440 ng⋅h/mL. The C_max and AUC of elacestrant increase more than dose-proportional between 43 mg and 862 mg once daily (0.125 to 2.5 times the approved recommended dosage). By day 6, elacestrant reaches steady-state and has a 2-fold mean accumulation ratio based on AUC_0-24h. The t_max of elacestrant goes from 1 to 4 hr, and its oral bioavailability is approximately 10%. Compared to a fasted state, the C_max and AUC of elacestrant (345 mg) were 42% and 22% higher, respectively, when administered with a high-fat meal (800 to 1000 calories, 50% fat).⁸

Volume of distribution

Elacestrant has an apparent volume of distribution of 5800 L.⁸

Protein binding

Elacestrant has a protein plasma binding higher than 99% and independent of concentration.⁸

Metabolism

Elacestrant is metabolized in the liver, mainly by CYP3A4 and, to a lesser extent, by CYP2A6 and CYP2C9.⁸

Route of elimination

Elacestrant is mainly eliminated through feces and urine. Approximately 82% was recovered in feces (34% unchanged), and 7.5% was recovered in urine (< 1% unchanged) following a single radiolabeled oral dose of 345 mg.⁸

Half-life

The elimination half-life of elacestrant is 30 to 50 hours.⁸

Clearance

Elacestrant has an estimated clearance of 186 L/hr and a renal clearance of ≤ 0.14 L/hr.⁸

Adverse Effects

Improve decision support & research outcomes

With structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!

See the data

Improve decision support & research outcomes with our structured adverse effects data.

See a data sample

Toxicity

Toxicity information regarding elacestrant is not readily available. Patients experiencing an overdose are at an increased risk of severe adverse effects such as dyslipidemia and gastrointestinal disorders.⁸ Symptomatic and supportive measures are recommended. The carcinogenicity of elacestrant has not been evaluated. Elacestrant did not show mutagenicity in the in vitro Ames assay and was negative for clastogenicity in in vitro chromosome aberration assays and the in vivo rat bone marrow micronucleus assay.⁸

Fertility studies with elacestrant in animals have not been performed. Rats and cynomolgus monkeys presented adverse reactions in female reproductive organs including atrophy of the vagina, cervix, and uterus and follicular cysts in the ovary after receiving repeated doses of elacestrant. Male rats presented decreased cellularity of Leydig cells and degeneration/atrophy of the seminiferous epithelium in the testis.⁸

Pathways

Not Available

Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">

Not Available

Interactions

Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">

This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.

• Approved
• Vet approved
• Nutraceutical
• Illicit
• Withdrawn
• Investigational
• Experimental
• All Drugs

Drug	Interaction
Integrate drug-drug interactions in your software
Abametapir	The serum concentration of Elacestrant can be increased when it is combined with Abametapir.
Abemaciclib	The serum concentration of Abemaciclib can be increased when it is combined with Elacestrant.
Afatinib	The serum concentration of Afatinib can be increased when it is combined with Elacestrant.
Allopurinol	The serum concentration of Allopurinol can be increased when it is combined with Elacestrant.
Alpelisib	The serum concentration of Alpelisib can be increased when it is combined with Elacestrant.

Food Interactions

• Take with food. Take with food to reduce nausea and vomiting.

Products

Drug product information from 10+ global regions

Our datasets provide approved product information including:
dosage, form, labeller, route of administration, and marketing period.

Access now

Access drug product information from over 10 global regions.

Access now

International/Other Brands

Orserdu (Stemline Therapeutics)

Brand Name Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End	Region	Image
Orserdu	Tablet, film coated	86 mg/1	Oral	Stemline Therapeutics, Inc.	2023-01-27	Not applicable
Orserdu	Tablet, film coated	345 mg/1	Oral	Stemline Therapeutics, Inc.	2023-01-27	Not applicable

Categories

Drug Categories

• Antineoplastic Agents
• Antineoplastic and Immunomodulating Agents
• BCRP/ABCG2 Inhibitors
• Cytochrome P-450 CYP2A6 Substrates
• Cytochrome P-450 CYP2C9 Substrates
• Cytochrome P-450 CYP3A Substrates
• Cytochrome P-450 CYP3A4 Substrates
• Cytochrome P-450 Substrates
• Endocrine Therapy
• Estrogen Receptor Antagonists
• Estrogens, Non-Steroidal
• Naphthalenes
• OATP2B1/SLCO2B1 substrates
• P-glycoprotein inhibitors
• Selective Estrogen Receptor Degraders

Classification

Not classified

Affected organisms

• Humans and other mammals

Chemical Identifiers

UNII

FM6A2627A8

CAS number

722533-56-4

InChI Key

SIFNOOUKXBRGGB-AREMUKBSSA-N

InChI

InChI=1S/C30H38N2O2/c1-4-31-17-16-22-6-8-23(9-7-22)21-32(5-2)30-20-28(34-3)14-15-29(30)26-11-10-25-19-27(33)13-12-24(25)18-26/h6-9,12-15,19-20,26,31,33H,4-5,10-11,16-18,21H2,1-3H3/t26-/m1/s1

IUPAC Name

(6R)-6-{2-[ethyl({4-[2-(ethylamino)ethyl]phenyl}methyl)amino]-4-methoxyphenyl}-5,6,7,8-tetrahydronaphthalen-2-ol

SMILES

CCNCCC1=CC=C(CN(CC)C2=C(C=CC(OC)=C2)[C@@H]2CCC3=CC(O)=CC=C3C2)C=C1

References

Synthesis Reference

Cruskie MP, et al. (2019). Polymorphic forms of RAD1901-2HCl (U.S. Patent No. 10,385,008 B2). U.S. Patent and Trademark Office. https://patentimages.storage.googleapis.com/42/82/b6/e9fcbbbd08054e/US10385008.pdf

General References

1. Lloyd MR, Wander SA, Hamilton E, Razavi P, Bardia A: Next-generation selective estrogen receptor degraders and other novel endocrine therapies for management of metastatic hormone receptor-positive breast cancer: current and emerging role. Ther Adv Med Oncol. 2022 Jul 30;14:17588359221113694. doi: 10.1177/17588359221113694. eCollection 2022. [Article]
2. Garner F, Shomali M, Paquin D, Lyttle CR, Hattersley G: RAD1901: a novel, orally bioavailable selective estrogen receptor degrader that demonstrates antitumor activity in breast cancer xenograft models. Anticancer Drugs. 2015 Oct;26(9):948-56. doi: 10.1097/CAD.0000000000000271. [Article]
3. Bihani T, Patel HK, Arlt H, Tao N, Jiang H, Brown JL, Purandare DM, Hattersley G, Garner F: Elacestrant (RAD1901), a Selective Estrogen Receptor Degrader (SERD), Has Antitumor Activity in Multiple ER(+) Breast Cancer Patient-derived Xenograft Models. Clin Cancer Res. 2017 Aug 15;23(16):4793-4804. doi: 10.1158/1078-0432.CCR-16-2561. Epub 2017 May 4. [Article]
4. Patel HK, Tao N, Lee KM, Huerta M, Arlt H, Mullarkey T, Troy S, Arteaga CL, Bihani T: Elacestrant (RAD1901) exhibits anti-tumor activity in multiple ER+ breast cancer models resistant to CDK4/6 inhibitors. Breast Cancer Res. 2019 Dec 18;21(1):146. doi: 10.1186/s13058-019-1230-0. [Article]
5. Bidard FC, Kaklamani VG, Neven P, Streich G, Montero AJ, Forget F, Mouret-Reynier MA, Sohn JH, Taylor D, Harnden KK, Khong H, Kocsis J, Dalenc F, Dillon PM, Babu S, Waters S, Deleu I, Garcia Saenz JA, Bria E, Cazzaniga M, Lu J, Aftimos P, Cortes J, Liu S, Tonini G, Laurent D, Habboubi N, Conlan MG, Bardia A: Elacestrant (oral selective estrogen receptor degrader) Versus Standard Endocrine Therapy for Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: Results From the Randomized Phase III EMERALD Trial. J Clin Oncol. 2022 Oct 1;40(28):3246-3256. doi: 10.1200/JCO.22.00338. Epub 2022 May 18. [Article]
6. Chinnasamy K, Saravanan M, Poomani K: Investigation of binding mechanism and downregulation of elacestrant for wild and L536S mutant estrogen receptor-alpha through molecular dynamics simulation and binding free energy analysis. J Comput Chem. 2020 Jan 15;41(2):97-109. doi: 10.1002/jcc.26076. Epub 2019 Oct 10. [Article]
7. Lu Y, Liu W: Selective Estrogen Receptor Degraders (SERDs): A Promising Strategy for Estrogen Receptor Positive Endocrine-Resistant Breast Cancer. J Med Chem. 2020 Dec 24;63(24):15094-15114. doi: 10.1021/acs.jmedchem.0c00913. Epub 2020 Nov 2. [Article]
8. FDA Approved Drug Products: ORSERDU (elacestrant) tablets for oral use [Link]
9. BioSpace: Stemline Therapeutics Receives U.S. FDA Approval for ORSERDUTM (elacestrant) as the First and Only Treatment Specifically Indicated for Patients with ESR1 Mutations in ER+, HER2- Advanced or Metastatic Breast Cancer [Link]
10. EMA Summary of Product Characteristics: Orserdu (elacestrant) film-coated tablets for oral administration [Link]
11. NewsWire: European Commission Approves Menarini Group's ORSERDU® (Elacestrant) for the Treatment of Patients with ER+, HER2- Locally Advanced or Metastatic Breast Cancer with an Activating ESR1 Mutation [Link]

External Links

ChemSpider

57583807

BindingDB

349630

RxNav

2628469

ChEMBL

CHEMBL4297509

PDBe Ligand

I0V

Wikipedia

Elacestrant

PDB Entries

7te7

Clinical Trials

Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">

Phase	Status	Purpose	Conditions	Count
3	Active Not Recruiting	Treatment	Breast Cancer	1
3	Recruiting	Treatment	Breast Cancer, Stage III / Estrogen Receptor Positive Breast Cancer / Human Epidermal Growth Factor 2 Negative Carcinoma of Breast / Stage IIB Breast Cancer	1
2	Completed	Treatment	Hot Flashes	1
2	Not Yet Recruiting	Treatment	Advanced Breast Cancerv / Estrogen Receptor Positive Breast Cancer / HER2/Neu-Negative Breast Cancer / Metastatic Breast Cancer	1
2	Not Yet Recruiting	Treatment	Advanced or Metastatic Breast Cancer / BRCA 1 Gene Mutation / BRCA 2 Gene Mutation / Hormone Receptor Positive (HR+), HER2-negative Breast Cancer / PALB2 Gene Mutation	1

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Not Available

Dosage Forms

Form	Route	Strength
Tablet, film coated	Oral	345 mg
Tablet, film coated	Oral	345 mg/1
Tablet, film coated	Oral	86 mg/1
Tablet, film coated	Oral	86 mg

Prices

Not Available

Patents

Patent Number	Pediatric Extension	Approved	Expires (estimated)	Region
US10745343	No	2020-08-18	2038-01-05
US10071066	No	2018-09-11	2034-10-10
US8399520	No	2013-03-19	2023-12-25
US10385008	No	2019-08-20	2038-01-05
US7612114	No	2009-11-03	2026-08-18
US10420734	No	2019-09-24	2034-10-10
US11779552	No	2014-10-10	2034-10-10
US11819480	No	2016-11-29	2036-11-29

Properties

State

Solid

Experimental Properties

Not Available

Predicted Properties

Property	Value	Source
Water Solubility	0.00035 mg/mL	ALOGPS
logP	6.54	ALOGPS
logP	6.23	Chemaxon
logS	-6.1	ALOGPS
pKa (Strongest Acidic)	10.58	Chemaxon
pKa (Strongest Basic)	9.96	Chemaxon
Physiological Charge	1	Chemaxon
Hydrogen Acceptor Count	4	Chemaxon
Hydrogen Donor Count	2	Chemaxon
Polar Surface Area	44.73 Å2	Chemaxon
Rotatable Bond Count	10	Chemaxon
Refractivity	143.17 m3·mol-1	Chemaxon
Polarizability	55.16 Å3	Chemaxon
Number of Rings	4	Chemaxon
Bioavailability	1	Chemaxon
Rule of Five	No	Chemaxon
Ghose Filter	No	Chemaxon
Veber's Rule	No	Chemaxon
MDDR-like Rule	Yes	Chemaxon

Predicted ADMET Features

Not Available

Spectra

Mass Spec (NIST)

Not Available

Spectra

Spectrum	Spectrum Type	Splash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)	Predicted LC-MS/MS	splash10-0a4i-0000900000-85c880e009d623649b96
Predicted MS/MS Spectrum - 10V, Negative (Annotated)	Predicted LC-MS/MS	splash10-0a4i-0000900000-1a10731637b7e10174c4
Predicted MS/MS Spectrum - 20V, Positive (Annotated)	Predicted LC-MS/MS	splash10-08fs-0404900000-84dbe4b6ee7b5ef660e0
Predicted MS/MS Spectrum - 20V, Negative (Annotated)	Predicted LC-MS/MS	splash10-0a4i-0002900000-51e6b3245d68539f5b76
Predicted MS/MS Spectrum - 40V, Positive (Annotated)	Predicted LC-MS/MS	splash10-0ce9-2915400000-40d400b3b8773eadda97
Predicted MS/MS Spectrum - 40V, Negative (Annotated)	Predicted LC-MS/MS	splash10-03ej-0129700000-bce86b5346d3af8aa08e
Predicted 1H NMR Spectrum	1D NMR	Not Applicable
Predicted 13C NMR Spectrum	1D NMR	Not Applicable

Chromatographic Properties

Collision Cross Sections (CCS)

Not Available

Targets

Build, predict & validate machine-learning models

Use our structured and evidence-based datasets to unlock new
insights and accelerate drug research.

Learn more

Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.

Learn more

Details1. Estrogen receptor alpha

Kind

Protein

Organism

Humans

Pharmacological action

Unknown

Actions

Antagonist

General Function

Zinc ion binding

Specific Function

Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissu...

Gene Name

ESR1

Uniprot ID

P03372

Uniprot Name

Estrogen receptor

Molecular Weight

66215.45 Da

References

1. Garner F, Shomali M, Paquin D, Lyttle CR, Hattersley G: RAD1901: a novel, orally bioavailable selective estrogen receptor degrader that demonstrates antitumor activity in breast cancer xenograft models. Anticancer Drugs. 2015 Oct;26(9):948-56. doi: 10.1097/CAD.0000000000000271. [Article]
2. Chinnasamy K, Saravanan M, Poomani K: Investigation of binding mechanism and downregulation of elacestrant for wild and L536S mutant estrogen receptor-alpha through molecular dynamics simulation and binding free energy analysis. J Comput Chem. 2020 Jan 15;41(2):97-109. doi: 10.1002/jcc.26076. Epub 2019 Oct 10. [Article]
3. FDA Approved Drug Products: ORSERDU (elacestrant) tablets for oral use [Link]

×

Identify potential medication risks

Easily compare up to 40 drugs with our drug interaction checker.

Get severity rating, description, and management advice.

Learn more

Drug created at March 19, 2008 16:28 / Updated at December 22, 2023 19:51