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Details

Stereochemistry ACHIRAL
Molecular Formula C26H20ClFN2O2
Molecular Weight 446.901
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 2
Charge 0

SHOW SMILES / InChI
Structure of BRILANESTRANT

SMILES

CC\C(=C(\C1=CC=C(\C=C\C(O)=O)C=C1)C2=CC3=C(NN=C3)C=C2)C4=CC=C(F)C=C4Cl

InChI

InChIKey=BURHGPHDEVGCEZ-KJGLQBJMSA-N
InChI=1S/C26H20ClFN2O2/c1-2-21(22-10-9-20(28)14-23(22)27)26(18-8-11-24-19(13-18)15-29-30-24)17-6-3-16(4-7-17)5-12-25(31)32/h3-15H,2H2,1H3,(H,29,30)(H,31,32)/b12-5+,26-21+

HIDE SMILES / InChI

Molecular Formula C26H20ClFN2O2
Molecular Weight 446.901
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 2
Optical Activity NONE

ARN-810 (GDC-0810) is a novel, orally bioavailable, estrogen receptor antagonist that induces proteasomal estrogen receptor degradation in breast cancer cell lines at picomolar concentrations and tumor regression in tamoxifen-sensitive and resistant BC xenograft models. Results from a first-in-human phase I/IIa study of ARN-810 indicate that it is tolerable and may benefit some postmenopausal women with advanced estrogen receptor-positive breast cancer. Development of ARN-810 was discontinued.

Approval Year

Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
25 μg/mL
600 mg 1 times / day steady-state, oral
dose: 600 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
GDC-0810 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
18.4 μg/mL
800 mg 1 times / day steady-state, oral
dose: 800 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
GDC-0810 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
22.2 μg/mL
600 mg single, oral
dose: 600 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
GDC-0810 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
15.9 μg/mL
800 mg single, oral
dose: 800 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
GDC-0810 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
102 μg × h/mL
600 mg 1 times / day steady-state, oral
dose: 600 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
GDC-0810 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
80.4 μg × h/mL
800 mg 1 times / day steady-state, oral
dose: 800 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
GDC-0810 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
114 μg × h/mL
600 mg single, oral
dose: 600 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
GDC-0810 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
65.7 μg × h/mL
800 mg single, oral
dose: 800 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
GDC-0810 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
7.91 h
600 mg single, oral
dose: 600 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
GDC-0810 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
10.1 h
800 mg single, oral
dose: 800 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
GDC-0810 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
Overview

Overview

Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
moderate [IC50 2.2 uM]
moderate [IC50 3.3 uM]
no [IC50 >20 uM]
no [IC50 >20 uM]
no [IC50 >20 uM]
unlikely
yes [IC50 0.913 uM]
yes (co-administration study)
Comment: Increased Pravastatin Cmax and AUCinf by 19.8% and 40.7%.
yes [IC50 <0.1 uM]
yes [IC50 <0.3 uM]
yes (co-administration study)
Comment: Increased Pravastatin Cmax and AUCinf by 19.8% and 40.7%.
yes
Drug as victimTox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Evaluating an ER Degrader for Breast Cancer.
2015 Jul
Identification of GDC-0810 (ARN-810), an Orally Bioavailable Selective Estrogen Receptor Degrader (SERD) that Demonstrates Robust Activity in Tamoxifen-Resistant Breast Cancer Xenografts.
2015 Jun 25
Novel Selective Estrogen Receptor Downregulators (SERDs) Developed against Treatment-Resistant Breast Cancer.
2017 Feb 23
Patents

Sample Use Guides

ARN-810 was tested using standard 3+3 dose escalation to assess safety, PK, and Recommended Phase 2 Dose (RP2D). Key eligibility criteria included ER+ (HER2-) metastatic BC progressing ≥ 6 months (m) on endocrine therapy and ≤ 2 prior chemotherapies. From April 2013 to June 2014, 32 patients (pts) (median age 61 (range 43 – 75); median number of prior therapies = 3 (range 1 – 7); visceral metastases 54%) were enrolled at 5 doses (100, 200, 400, 600, 800 mg) and 2 different regimens (once [QD] and twice daily) given orally with and without fasting. The drug is undergoing further evaluation in a phase II study, at a recommended dose of 600 mg.
Route of Administration: Oral
In Vitro Use Guide
Curator's Comment: ARN-810 is a novel, orally bioavailable, estrogen receptor antagonist that induces proteasomal estrogen receptor degradation in breast cancer cell lines at picomolar concentrations and tumor regression in tamoxifen-sensitive and resistant breast cancer xenograft models.
Unknown
Substance Class Chemical
Created
by admin
on Sat Dec 16 09:03:13 UTC 2023
Edited
by admin
on Sat Dec 16 09:03:13 UTC 2023
Record UNII
9MM2R1A06R
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
BRILANESTRANT
INN   WHO-DD  
INN  
Official Name English
Brilanestrant [WHO-DD]
Common Name English
RG-6046
Code English
2-PROPENOIC ACID, 3-(4-((1E)-2-(2-CHLORO-4-FLUOROPHENYL)-1-(1H-INDAZOL-5-YL)-1-BUTEN-1-YL)PHENYL)-, (2E)-
Systematic Name English
(2E)-3-(4-((1E)-2-(2-CHLORO-4-FLUOROPHENYL)-1-(1H-INDAZOL-5-YL)-1-BUTEN-1-YL)PHENYL)-2-PROPENOIC ACID
Systematic Name English
BRILANESTRANT [USAN]
Common Name English
brilanestrant [INN]
Common Name English
ARN-810
Code English
(2E)-3-(4-((1E)-2-(2-CHLORO-4-FLUOROPHENYL)-1-(1H-INDAZOL- 5-YL)BUT-1-EN-1-YL)PHENYL)PROP-2-ENOIC ACID
Systematic Name English
GDC-0810
Code English
Classification Tree Code System Code
NCI_THESAURUS C2116
Created by admin on Sat Dec 16 09:03:14 UTC 2023 , Edited by admin on Sat Dec 16 09:03:14 UTC 2023
Code System Code Type Description
ChEMBL
CHEMBL3545390
Created by admin on Sat Dec 16 09:03:14 UTC 2023 , Edited by admin on Sat Dec 16 09:03:14 UTC 2023
PRIMARY
WIKIPEDIA
Brilanestrant
Created by admin on Sat Dec 16 09:03:14 UTC 2023 , Edited by admin on Sat Dec 16 09:03:14 UTC 2023
PRIMARY
SMS_ID
100000170614
Created by admin on Sat Dec 16 09:03:14 UTC 2023 , Edited by admin on Sat Dec 16 09:03:14 UTC 2023
PRIMARY
MANUFACTURER PRODUCT INFORMATION
BRILANESTRANT
Created by admin on Sat Dec 16 09:03:14 UTC 2023 , Edited by admin on Sat Dec 16 09:03:14 UTC 2023
PRIMARY MedKoo CAT NO.: 206041, CAS N).: 1365888-06-7Description: GDC-0810, also known as ARN-810 and RG6046, an orally bioavailable Selective Estrogen Receptor Degrader (SERD) that demonstrates robust activity in tamoxifen-resistant breast cancer xenografts. GDC-0810 functions by binding to the estrogen receptor, inducing a conformational change resulting in the degradation of the receptor. GDC-0810 or ARN-810 demonstrates robust activity in models of tamoxifen-sensitive and tamoxifen-resistant breast cancer, and is currently in clinical trials in women with locally advanced or metastatic estrogen receptor-positive breast cancer. (Last update: 6/16/2016)Synonyms: GDC0810, GDC 0810, GDC-0810, ARN810, ARN 810, ARN-810, RG6046, RG-6046, RG 6046.
INN
10283
Created by admin on Sat Dec 16 09:03:14 UTC 2023 , Edited by admin on Sat Dec 16 09:03:14 UTC 2023
PRIMARY
DRUG BANK
DB12253
Created by admin on Sat Dec 16 09:03:14 UTC 2023 , Edited by admin on Sat Dec 16 09:03:14 UTC 2023
PRIMARY
FDA UNII
9MM2R1A06R
Created by admin on Sat Dec 16 09:03:14 UTC 2023 , Edited by admin on Sat Dec 16 09:03:14 UTC 2023
PRIMARY
EVMPD
SUB184646
Created by admin on Sat Dec 16 09:03:14 UTC 2023 , Edited by admin on Sat Dec 16 09:03:14 UTC 2023
PRIMARY
PUBCHEM
56941241
Created by admin on Sat Dec 16 09:03:14 UTC 2023 , Edited by admin on Sat Dec 16 09:03:14 UTC 2023
PRIMARY
EPA CompTox
DTXSID701336037
Created by admin on Sat Dec 16 09:03:14 UTC 2023 , Edited by admin on Sat Dec 16 09:03:14 UTC 2023
PRIMARY
NCI_THESAURUS
C106235
Created by admin on Sat Dec 16 09:03:14 UTC 2023 , Edited by admin on Sat Dec 16 09:03:14 UTC 2023
PRIMARY
USAN
EF-76
Created by admin on Sat Dec 16 09:03:14 UTC 2023 , Edited by admin on Sat Dec 16 09:03:14 UTC 2023
PRIMARY
CAS
1365888-06-7
Created by admin on Sat Dec 16 09:03:14 UTC 2023 , Edited by admin on Sat Dec 16 09:03:14 UTC 2023
PRIMARY
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