1365888-06-7

Basic information

• Product Name: GDC-0810(ARN-810)
• Synonyms: GDC-0810(ARN-810);GDC-0810;(E)-3-[4-[(E)-2-(2-Chloro-4-fluorophenyl)-1-(1H-indazol-5-yl)but-1-en-1-yl]phenyl]-2-propenoic acid;GDC-0810 (Brilanestrant)
• CAS NO: 1365888-06-7
• Molecular Formula: C₂₆H₂₀ClFN₂O₂
• Molecular Weight: 446.9006032
• EINECS: -0
• Mol File: 1365888-06-7.mol
• Article Data: 4

Chemical Properties

• Boiling Point: 622.8±55.0 °C(Predicted)
• Appearance: /
• Density: 1.342±0.06 g/cm3(Predicted)
• PKA: 13.94±0.40(Predicted)
• CAS DataBase Reference: GDC-0810(ARN-810)(CAS DataBase Reference)
• NIST Chemistry Reference: GDC-0810(ARN-810)(1365888-06-7)
• EPA Substance Registry System: GDC-0810(ARN-810)(1365888-06-7)

Safety Data

• Hazardous Substances Data: 1365888-06-7(Hazardous Substances Data)

Usage

Description

GDC-0810 (ARN-810) is a novel, orally bioavailable Selective Estrogen Receptor Degrader (SERD) that has shown significant promise in the treatment of breast cancer. It works by binding to the estrogen receptor, inducing a conformational change that leads to the degradation of the receptor. This innovative approach has demonstrated robust activity in both tamoxifen-sensitive and tamoxifen-resistant breast cancer models.

Uses

Used in Pharmaceutical Industry:
GDC-0810 (ARN-810) is used as an anticancer agent for the treatment of breast cancer. It is particularly effective against tamoxifen-resistant breast cancer xenografts, making it a valuable addition to the arsenal of treatments for this disease. The compound's ability to induce the degradation of the estrogen receptor has shown potential in overcoming resistance to traditional hormone therapies, such as tamoxifen.
Additionally, GDC-0810 (ARN-810) is currently in clinical trials for women with locally advanced or metastatic estrogen receptor-positive breast cancer. This further underscores its potential as a valuable therapeutic option for patients with this type of cancer.

Upstream product

• 1082525-64-1 1-(tetrahydro-2H-pyran-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazole 
• 177985-32-9 2-(2-chloro-4-fluorophenyl)acetic acid 
• 619-42-1 4-methoxycarbonylphenyl bromide 
• 101335-11-9 2-chloro-4-fluoro-1-iodobenzene 
• 1365889-11-7 ethyl (E)-3-(4-((E)-2-(2-chloro-4-fluorophenyl)-1-(1H-indazol-5-yl)but-1-en-1-yl)phenyl)acrylate 
• 15164-44-0 p-(iodophenyl)carboxaldehyde 
• 1365889-10-6 (E)-ethyl 3-(4-((E)-2-(2-chloro-4-fluorophenyl)-1-(1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-5-yl)but-1-en-1-yl)phenyl)acrylate 
• 1365889-09-3 (E)-4-(2-(2-chloro-4-fluorophenyl)-1-(1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-5-yl)but-1-en-1-yl)benzaldehyde 
• 1365889-59-3 (E)-ethyl 3-(4-((E)-2-(2-chloro-4-fluorophenyl)-1-(1H-indazol-5-yl)but-1-en-1-yl)phenyl)acrylate hydrochloride 
• 1365889-00-4 5-(but-1-yn-1-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole 
• 1365888-98-7 1-(tetrahydro-2H-pyran-2-yl)-5-((trimethylsilyl)ethynyl)-1H-indazole 

Relevant articles and documents

Synthesis of Selective Estrogen Receptor Degrader GDC-0810 via Stereocontrolled Assembly of a Tetrasubstituted All-Carbon Olefin

We report an efficient synthesis of GDC-0810 on the basis of a sequence involving a highly stereoselective lithium tert-butoxide-mediated enolization-tosylation (≥95:5 E:Z) and a Pd-catalyzed Suzuki-Miyaura cross-coupling as key steps. Global deprotection, pyrrolidine salt formation, and final active pharmaceutical ingredient (API) form control/isolation produced GDC-0810 free acid in a 40% overall yield with >99.0% purity as ascertained by HPLC analysis.

Identification of GDC-0810 (ARN-810), an Orally Bioavailable Selective Estrogen Receptor Degrader (SERD) that Demonstrates Robust Activity in Tamoxifen-Resistant Breast Cancer Xenografts

Approximately 80% of breast cancers are estrogen receptor alpha (ER-α) positive, and although women typically initially respond well to antihormonal therapies such as tamoxifen and aromatase inhibitors, resistance often emerges. Although a variety of resistance mechanism may be at play in this state, there is evidence that in many cases the ER still plays a central role, including mutations in the ER leading to constitutively active receptor. Fulvestrant is a steroid-based, selective estrogen receptor degrader (SERD) that both antagonizes and degrades ER-α and is active in patients who have progressed on antihormonal agents. However, fulvestrant suffers from poor pharmaceutical properties and must be administered by intramuscular injections that limit the total amount of drug that can be administered and hence lead to the potential for incomplete receptor blockade. We describe the identification and characterization of a series of small-molecule, orally bioavailable SERDs which are potent antagonists and degraders of ER-α and in which the ER-α degrading properties were prospectively optimized. The lead compound 11l (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.