elacestrant 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | BioActivity |

Stem definitionDrug idCAS RN
estrogen antagonists, including estrogen receptor down-regulators 5710 722533-56-4

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • elacestrant
  • elacestrant dihydrochloride
  • orserdu
  • RAD1901
Elacestrant is an estrogen receptor antagonist that binds to estrogen receptor-alpha (ERalfa). In ER-positive (ER+) HER2-negative (HER2-) breast cancer cells, elacestrant inhibited 17beta-estradiol mediated cell proliferation at concentrations inducing degradation of ERalfa protein mediated through proteasomal pathway. Elacestrant demonstrated in vitro and in vivo antitumor activity including in ER+ HER2- breast cancer models resistant to fulvestrant and cyclin-dependent kinase 4/6 inhibitors and those harboring estrogen receptor 1 gene (ESR1) mutations.
  • Molecular weight: 458.65
  • Formula: C30H38N2O2
  • CLOGP: 5.85
  • LIPINSKI: 1
  • HAC: 4
  • HDO: 2
  • TPSA: 44.73
  • ALOGS:
  • ROTB: 10
  • Status: ONP
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

None

ADMET properties:

None

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 3.727 High 1
caco2-efflux Caco-2 efflux ratio (BA/AB) 22.182 High 1
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 0.724 10^-6 cm/s High 1
dh-clint Dog hepatocyte intrinsic clearance 13.459 uL/min/10^6 cells High 1
dppb Dog plasma protein binding (% unbound) 0.090 % High 1
fcs-ppb Fetal calf serum protein binding (% unbound) 1.330 % High 1
herg hERG pIC50 5.271 pIC50 High 1
hh-clint Human hepatocyte intrinsic clearance 7.379 uL/min/10^6 cells High 1
hlm-clint Human liver microsomal intrinsic clearance 11.722 uL/min/mg protein High 1
hppb Human plasma protein binding (% unbound) 0.200 % High 1
kinase-safety-class ACVR2A,ACVR2B,ACVRL1,AKT1,AKT2,AKT3,ALK,AURKA,AXL,BRAF,BTK,CAMK2B,CAMK2D,CDK4,CDK5,CDK9,CHEK1,DDR1,DYRK1B,EGFR,EIF2AK3,EPHB4,ERBB2,FLT3,GRK2,IGF1R,INSR,ITK,JAK1,JAK2,JAK3,KIT,MAP2K6,MAP3K1,MAP3K21,MAP3K7,MAP4K1,MAP4K3,MAPK10,MAPK7,MAPK9,MAPKAPK2,MARK4,MELK,MET,MTOR,NTRK2,PAK4,PDK1,PDK2,PDK4,PDPK1,PIK3CA,PIK3CB,PIK3CD,PIM2,PRKCD,PRKDC,SIK2,SIK3,STK33,SYK,TEK,TGFBR1,TTK,ULK1,ZAP70 67
kinase-selectivity-class AXL,BRAF,EIF2AK3,EPHB4,GRK2,MAP2K6,PDK4 7
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 9.484 High 1
mh-clint Mouse hepatocyte intrinsic clearance 77.446 High 1
mppb Mouse plasma protein binding (% unbound) 0.130 High 1
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 32.285 High 1
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pppb Pig plasma protein binding (% unbound) 0.960 % High 1
rat-kpuu-brain Rat brain Kpuu 0.080 % High 1
rh-clint Rat hepatocyte intrinsic clearance 50.119 uL/min/10^6 cells High 1
rh-fuinc Rat hepatocyte fraction unbound in incubation 0.300 % High 1
rppb Rat plasma protein binding (% unbound) 0.140 % High 1
solubility-dd Solubility at pH 7.4 in DMSO 4.140 uM High 1

Approvals:

DateAgencyCompanyOrphan
Jan. 27, 2023 FDA STEMLINE THERAPEUTICS INC
Sept. 15, 2023 EMA Stemline Therapeutics B.V.

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Disease progression 1219.50 48.69 305 1049 156310 90470783
Death 347.66 48.69 156 1198 456395 90170698
Nausea 108.33 48.69 105 1249 1110211 89516882
Hospice care 104.13 48.69 25 1329 9679 90617414
Tumour marker increased 57.33 48.69 14 1340 5793 90621300

FDA Adverse Event Reporting System (Male)

None

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Disease progression 1085.88 52.14 286 938 243748 110344327
Death 326.67 52.14 155 1069 698714 109889361
Hospice care 105.37 52.14 25 1199 12448 110575627
Nausea 88.01 52.14 86 1138 1235604 109352471
Tumour marker increased 63.44 52.14 14 1210 5046 110583029

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC L02BA04 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ENDOCRINE THERAPY
HORMONE ANTAGONISTS AND RELATED AGENTS
Anti-estrogens
MeSH PA D000970 Antineoplastic Agents
FDA MoA N0000000145 Estrogen Receptor Antagonists
FDA EPC N0000175582 Estrogen Receptor Antagonist
FDA MoA N0000185503 P-Glycoprotein Inhibitors
FDA MoA N0000190113 Breast Cancer Resistance Protein Inhibitors
CHEBI has role CHEBI:35610 antineoplastic agent
CHEBI has role CHEBI:50751 anti-estrogen
CHEBI has role CHEBI:50792 estrogen receptor antagonist

Related Drugs by ATC class:

L02BA Anti-estrogens 3 drugs
fulvestranttamoxifentoremifene

Drug Use | Suggest Off label Use Form| |View source of the data|

DiseaseRelationSNOMED_IDDOID
Estrogen receptor positive advanced or metastatic breast cancer indication 254837009 DOID:1612
HER2-negative advanced or metastatic breast cancer indication 254837009 DOID:1612
ESR1-mutated advanced or metastatic breast cancer indication 254837009 DOID:1612




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

None

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
EQ 86MG BASE ORSERDU STEMLINE THERAP N217639 Jan. 27, 2023 RX TABLET ORAL 7612114 Aug. 18, 2026 TREATMENT OF AN ER-POSITIVE BREAST CANCER
EQ 86MG BASE ORSERDU STEMLINE THERAP N217639 Jan. 27, 2023 RX TABLET ORAL 10071066 Oct. 10, 2034 TREATMENT OF AN ER-POSITIVE BREAST CANCER FOLLOWING AT LEAST ONE LINE OF ENDOCRINE THERAPY
EQ 86MG BASE ORSERDU STEMLINE THERAP N217639 Jan. 27, 2023 RX TABLET ORAL 11779552 Oct. 10, 2034 TREATMENT OF AN ER-POSITIVE BREAST CANCER FOLLOWING AT LEAST ONE LINE OF ENDOCRINE THERAPY
EQ 86MG BASE ORSERDU STEMLINE THERAP N217639 Jan. 27, 2023 RX TABLET ORAL 10420734 Oct. 3, 2036 TREATMENT OF AN ER-POSITIVE BREAST CANCER FOLLOWING AT LEAST ONE LINE OF ENDOCRINE THERAPY
EQ 86MG BASE ORSERDU STEMLINE THERAP N217639 Jan. 27, 2023 RX TABLET ORAL 11819480 Feb. 28, 2037 TREATMENT OF AN ER-POSITIVE BREAST CANCER
EQ 86MG BASE ORSERDU STEMLINE THERAP N217639 Jan. 27, 2023 RX TABLET ORAL 10745343 Jan. 5, 2038 TREATMENT OF AN ER-POSITIVE BREAST CANCER

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
EQ 86MG BASE ORSERDU STEMLINE THERAP N217639 Jan. 27, 2023 RX TABLET ORAL Jan. 27, 2028 NEW CHEMICAL ENTITY

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
Estrogen receptor Nuclear hormone receptor ANTAGONIST IC50 7.32 DRUG LABEL DRUG LABEL
Estrogen receptor beta Nuclear hormone receptor ANTAGONIST IC50 6.06 DRUG LABEL

External reference:

IDSource
CHEBI:229213 CHEBI
CHEMBL4297509 ChEMBL_ID
C000626176 MESH_SUPPLEMENTAL_RECORD_UI
12339 IUPHAR_LIGAND_ID
DB06374 DRUGBANK_ID
43186711000001103 SNOMEDCT_US
43186811000001106 SNOMEDCT_US
4042013 VANDF
C4682404 UMLSCUI
I0V PDB_CHEM_ID
CHEMBL4594273 ChEMBL_ID
10247 INN_ID
23642301 PUBCHEM_CID
364875 MMSL
41206 MMSL
d09981 MMSL
019283 NDDF
019284 NDDF
D11671 KEGG_DRUG
FM6A2627A8 UNII
2628469 RXNORM
C000626184 MESH_SUPPLEMENTAL_RECORD_UI
FM6A2627A8 INXIGHT DRUGS

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
ORSERDU HUMAN PRESCRIPTION DRUG LABEL 1 72187-0101 TABLET, FILM COATED 86 mg ORAL NDA 27 sections
ORSERDU HUMAN PRESCRIPTION DRUG LABEL 1 72187-0102 TABLET, FILM COATED 345 mg ORAL NDA 27 sections