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Elacestrant Pronunciation EL -ə-SES -trənt Trade names Orserdu Other names RAD-1901; ER-306323 License data
Routes of administration By mouth ATC code
Legal status
EU : Rx-only[3] [4]
Bioavailability ~10%[1] Protein binding >99%[1] Metabolism Liver (major: CYP3A4 , minor: CYP2A6 , CYP2C9 )[1] Elimination half-life 30–50 hours[1] Excretion Feces (82%), urine (7.5%)[1]
(6 R )-6-{2-[Ethyl({4-[2-(ethylamino)ethyl]phenyl}methyl)amino]-4-methoxyphenyl}-5,6,7,8-tetrahydronaphthalen-2-ol
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
PDB ligand
CompTox Dashboard (EPA )
ECHA InfoCard 100.312.890 Formula C 30 H 38 N 2 O 2 Molar mass 458.646 g·mol−1 3D model (JSmol )
CCNCCC1=CC=C(C=C1)CN(CC )C2=C(C=CC(=C2)OC)C3CCC4=C(C3)C=CC(=C4)O
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
Key:SIFNOOUKXBRGGB-AREMUKBSSA-N
Elacestrant , sold under the brand name Orserdu , is an anticancer medication which is used in the treatment of breast cancer .[1] [4] It is taken by mouth .[1] [4]
Elacestrant is an antiestrogen , or an antagonist of the estrogen receptors , the biological targets of endogenous estrogens such as estradiol .[1] The most common side effects of elacestrant include musculoskeletal pain , nausea , increased cholesterol , elevated liver enzymes , increased triglycerides , fatigue , decreased hemoglobin , vomiting , increased ALT , increased AST , decreased sodium , increased creatinine , decreased appetite , diarrhea , headache , constipation , abdominal pain , hot flashes , and upset stomach .[2]
Elacestrant was approved for medical use in the United States in January 2023,[1] [2] [5] [6] and in the European Union in September 2023.[3] [7]
Medical uses [ edit ]
Elacestrant is indicated for the treatment of postmenopausal women or adult men with estrogen receptor (ER )-positive, human epidermal growth factor receptor 2 (HER2)-negative, ESR1 -mutated advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy .[2] [4]
Pharmacology [ edit ]
Pharmacodynamics [ edit ]
Elacestrant is an antiestrogen , or an antagonist of the estrogen receptors , the biological targets of endogenous estrogens like estradiol .[1] It is specifically an antagonist of the estrogen receptor alpha (ERα).[1] Elacestrant is also a selective estrogen receptor degrader (SERD), in that it induces degradation of the ERα.[1] [8]
Pharmacokinetics [ edit ]
The oral bioavailability of elacestrant is approximately 10%.[1] Its plasma protein binding is greater than 99% and is independent of concentration.[1] Elacestrant is metabolized in the liver , primarily by the cytochrome P450 enzyme CYP3A4 and to a lesser extent by CYP2A6 and CYP2C9 .[1] The elimination half-life of elacestrant is 30 to 50 hours.[1] It is excreted 82% in feces and 7.5% in urine .[1]
History [ edit ]
Efficacy was evaluated in EMERALD (NCT03778931), a randomized, open-label, active-controlled, multicenter trial that enrolled 478 postmenopausal women and men with ER-positive, HER2-negative advanced or metastatic breast cancer of which 228 participants had ESR1 mutations.[2] Participants were required to have disease progression on one or two prior lines of endocrine therapy, including one line containing a CDK4/6 inhibitor.[2] Eligible participants could have received up to one prior line of chemotherapy in the advanced or metastatic setting.[2] Participants were randomized (1:1) to receive elacestrant 345 mg orally once daily (n=239) or investigator’s choice of endocrine therapy (n=239), which included fulvestrant (n=166) or an aromatase inhibitor (n=73).[2] Randomization was stratified by ESR1 mutation status (detected vs. not detected), prior treatment with fulvestrant (yes vs. no), and visceral metastasis (yes vs. no).[2] ESR1 mutational status was determined by blood circulating tumor deoxyribonucleic acid (ctDNA) using the Guardant360 CDx assay and was limited to ESR1 missense mutations in the ligand binding domain.[2]
The FDA granted the application for elacestrant priority review and fast track designations.[2]
Research [ edit ]
It is a nonsteroidal combined selective estrogen receptor modulator (SERM) and selective estrogen receptor degrader (SERD) (described as a "SERM/SERD hybrid (SSH)") that was discovered by Eisai and is under development by Radius Health and Takeda for the treatment estrogen receptor (ER )-positive advanced breast cancer .[9] Elacestrant has dose-dependent, tissue-selective estrogenic and antiestrogenic activities, with biphasic weak partial agonist activity at the ER at low doses and antagonist activity at higher doses.[10] It shows agonistic activity on bone and antagonistic activity on breast and uterine tissues.[11] Unlike the SERD fulvestrant, elacestrant is able to readily cross the blood-brain-barrier into the central nervous system , where it can target breast cancer metastases in the brain ,[10] [11] and is orally bioavailable and does not require intramuscular injection .[10] [11]
References [ edit ]
^ a b "Orserdu Product information" . Union Register of medicinal products . 18 September 2023. Retrieved 1 October 2023 .
^ a b c d "Orserdu EPAR" . European Medicines Agency (EMA) . 9 October 2023. Retrieved 9 October 2023 .
^ https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2023/217639Orig1s000ltr.pdf Archived 2023-02-02 at the Wayback Machine This article incorporates text from this source, which is in the public domain .
^ "Stemline Therapeutics Inc., a wholly owned subsidiary of Menarini Group, Receives Approval from U.S. FDA for Orserdu (elacestrant) as the First and Only Treatment Specifically Indicated for Patients with ESR1 Mutations in ER+, HER2- Advanced or Metastatic Breast Cancer" . Radius (Press release). 31 January 2023. Archived from the original on 2 February 2023. Retrieved 1 February 2023 .
^ "EC approves Menarini Group's Orserdu for advanced or metastatic breast cancer" . PMLive . 21 September 2023. Retrieved 22 September 2023 .
^ Lloyd MR, Wander SA, Hamilton E, Razavi P, Bardia A (2022). "Next-generation selective estrogen receptor degraders and other novel endocrine therapies for management of metastatic hormone receptor-positive breast cancer: current and emerging role" . Therapeutic Advances in Medical Oncology . 14 : 17588359221113694. doi :10.1177/17588359221113694 . PMC 9340905 . PMID 35923930 .
^ Clinical trial number NCT03778931 for "Phase 3 Trial of Elacestrant vs. Standard of Care for the Treatment of Patients With ER+/HER2- Advanced Breast Cancer" at ClinicalTrials.gov
^ a b c Wardell SE, Nelson ER, Chao CA, Alley HM, McDonnell DP (October 2015). "Evaluation of the pharmacological activities of RAD1901, a selective estrogen receptor degrader" . Endocrine-Related Cancer . 22 (5 ): 713–724. doi :10.1530/ERC-15-0287 . PMC 4545300 . PMID 26162914 .
^ a b c Garner F, Shomali M, Paquin D, Lyttle CR, Hattersley G (October 2015). "RAD1901: a novel, orally bioavailable selective estrogen receptor degrader that demonstrates antitumor activity in breast cancer xenograft models" . Anti-Cancer Drugs . 26 (9 ): 948–956. doi :10.1097/CAD.0000000000000271 . PMC 4560273 . PMID 26164151 .
t
e
Estrogens
ER Tooltip Estrogen receptor agonists
Steroidal: Alfatradiol
Certain androgens /anabolic steroids (e.g., testosterone , testosterone esters , methyltestosterone , metandienone , nandrolone esters ) (via estrogenic metabolites)
Certain progestins (e.g., norethisterone , noretynodrel , etynodiol diacetate , tibolone )
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Epimestrol
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Estetrol †
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ER Tooltip Estrogen receptor antagonists (incl. SERMs Tooltip selective estrogen receptor modulators /SERDs Tooltip selective estrogen receptor downregulators )
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GnRH antagonists (e.g., cetrorelix , elagolix )
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Clinical trials :
See also
Estrogen receptor modulators
Androgens and antiandrogens
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List of estrogens
t
e
ER Tooltip Estrogen receptor
Agonists
Steroidal: 2-Hydroxyestradiol
2-Hydroxyestrone
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Butolame
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ent -Estradiol
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Equilin
ERA-63 (ORG-37663)
Esterified estrogens
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RU-16117
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Tibolone
Xenoestrogens: Anise -related (e.g., anethole , anol , dianethole , dianol , photoanethole )
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Lavender oil
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Unknown
See also
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