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
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+
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
Cmax
Value | Dose | Co-administered | Analyte | Population |
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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 | Co-administered | 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 |
T1/2
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 |
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OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
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Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical 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%. Sources: https://pubmed.ncbi.nlm.nih.gov/29786857/ |
|||
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%. Sources: https://pubmed.ncbi.nlm.nih.gov/29786857/ |
|||
yes |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
major | ||||
minor | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
yes | ||||
yes | ||||
yes | ||||
yes |
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
PubMed
Title | Date | PubMed |
---|---|---|
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
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NCI_THESAURUS |
C2116
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CHEMBL3545390
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Brilanestrant
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100000170614
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BRILANESTRANT
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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. | ||
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10283
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DB12253
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SUB184646
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DTXSID701336037
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C106235
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EF-76
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1365888-06-7
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ACTIVE MOIETY
METABOLITE (PARENT)
METABOLITE (PARENT)
SALT/SOLVATE (PARENT)