BRILANESTRANT

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 Search

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

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/25879485 | http://cancerres.aacrjournals.org/content/75/9_Supplement/P1-13-01 | https://www.ncbi.nlm.nih.gov/pubmed/25956960 | http://www.roche.com/dam/jcr:08e82e2b-e257-4883-b00a-26475b7735f5/en/irp141111.pdf | https://endpts.com/roche-silently-whisks-away-its-1-7b-seragon-drug-in-a-q1-footnote/

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.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Estrogen receptor alpha 127 Target ID: CHEMBL206 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25879485 \| http://www.roche.com/dam/jcr:08e82e2b-e257-4883-b00a-26475b7735f5/en/irp141111.pdf	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Breast cancer 434 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25956960 https://www.ncbi.nlm.nih.gov/pubmed/25879485 http://cancerres.aacrjournals.org/content/75/9_Supplement/P1-13-01	Primary		Phase II 1132	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
25 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31266752	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31266752	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31266752	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31266752	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

Value	Dose	Analyte	Population
102 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31266752	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31266752	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31266752	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31266752	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

T_1/2

Value	Dose	Co-administered	Analyte	Population
7.91 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31266752	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31266752	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

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587	inhibitor 1767	inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
OATP1B1 788 OAT3 642 CYP2C19 1478 UGT 35 OATP1B3 706 CYP1A2 1524 CYP2C8 911	UGT1A1 418 UGT1A9 380 UGT 192 UGT1A4 347 UGT1A3 422 CYP3A 191 OATP1B3 350 OATP1B1 406 UGT1A6 307 UGT2B7 389 UGT2B15 203

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP2C9 1819	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/25879485/	moderate [IC50 2.2 uM]
CYP2C19 1553	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/25879485/	moderate [IC50 3.3 uM]
CYP1A2 1692	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/25879485/	no [IC50 >20 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/25879485/	no [IC50 >20 uM]
CYP3A4 1925	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/25879485/	no [IC50 >20 uM]
OAT3 644	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/29786857/	unlikely
OATP1B3 715	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/29786857/	yes [IC50 0.913 uM]	yes (co-administration study) Comment: Increased Pravastatin Cmax and AUCinf by 19.8% and 40.7%. Sources: https://pubmed.ncbi.nlm.nih.gov/29786857/
CYP2C8 965	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/25879485/	yes [IC50 <0.1 uM]
OATP1B1 803	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/29786857/	yes [IC50 <0.3 uM]	yes (co-administration study) Comment: Increased Pravastatin Cmax and AUCinf by 19.8% and 40.7%. Sources: https://pubmed.ncbi.nlm.nih.gov/29786857/
UGT 59	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/29786857/	yes

Drug as victim

Target	Modality	Activity
UGT 192	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/31266752/	major
CYP3A 191	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/29786857/	minor
OATP1B1 406	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/29786857/	no
OATP1B3 350	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/29786857/	no
UGT1A6 307	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/30335192/	no
UGT2B15 203	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/30335192/	no
UGT2B7 389	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/30335192/	no
UGT1A1 418	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/30335192/	yes
UGT1A3 422	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/30335192/	yes
UGT1A4 347	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/30335192/	yes
UGT1A9 380	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/30335192/	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://pubmed.ncbi.nlm.nih.gov/25879485/

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P0012K7	https://www.1pchem.com/search?query=1P0012K7
AChemBlock	M15900	http://www.achemblock.com/catalogsearch/result/?q=M15900
Angene	AGN-PC-0WALBM	http://www.angenechemical.com/productshow/AGN-PC-0WALBM.html
AstaTech	42353	http://astatechinc.com/CPSResult.php?CRNO=42353
BLD Pharm	BD304655	http://www.bldpharm.com/search/Search.html?keyword=BD304655
Chem Scene	CS-4588	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-4588
ChemShuttle	140500	https://www.chemshuttle.com/catalogsearch/result/?q=140500
Combi-Blocks	QV-5301	http://www.combi-blocks.com/cgi-bin/find.cgi?QV-5301
Excenen	EX-A2378	http://www.excenen.com/searchresultlist.php?id=EX-A2378
KeyOrganics	AS-74849	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-74849
MedChem Express	HY-12864	https://www.medchemexpress.com/search.html?q=HY-12864&ft=&fa=&fp=
MolPort	MolPort-039-137-735	https://www.molport.com/shop/molecule-link/MolPort-039-137-735
Molnova	M11510	https://www.molnova.com/en/serch-list.html?keywords=M11510
MuseChem	I001411	https://www.musechem.com/product/I001411.html
Selleck Chemicals	S7855	http://www.selleckchem.com/search.html?searchDTO.searchParam=S7855
ShangHai Biochempartner	BCP24812	http://www.biochempartner.com/search_BCP24812
TargetMol	T5118	https://www.targetmol.com/search?keyword=T5118
Toronto Research Chemicals	B677393	https://www.trc-canada.com/product-detail/?CatNum=B677393
eMolecules	302596156	https://orderbb.emolecules.com/search/#?query=302596156
eMolecules	64086790	https://orderbb.emolecules.com/search/#?query=64086790
eNovation Chemicals	D621100	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D621100&searchbtn.x=0&searchbtn.y=0
mcule	MCULE-1098049642	https://mcule.com/MCULE-1098049642/
mcule	MCULE-3811782730	https://mcule.com/MCULE-3811782730/

PubMed

Title	Date	PubMed
Evaluating an ER Degrader for Breast Cancer.	2015 Jul	25956960
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	25879485
Novel Selective Estrogen Receptor Downregulators (SERDs) Developed against Treatment-Resistant Breast Cancer.	2017 Feb 23	28117994

Patents

Sample Use Guides

In Vivo Use Guide

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

Unknown

Name

Type

Language

BRILANESTRANT

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