Name: ARV-471
Brand: BOC Sciences
Price: 599 USD
Availability: MadeToOrder

Size

Price

Stock

Quantity

5 mg

$599

In stock

Purity

≥95%

Solubility

Soluble in DMSO

Storage

Store at -20°C, sealed storage, away from moisture and light

IUPACName

(3S)-3-[6-[4-[[1-[4-[(1R,2S)-6-hydroxy-2-phenyl-1,2,3,4-tetrahydronaphthalen-1-yl]phenyl]piperidin-4-yl]methyl]piperazin-1-yl]-3-oxo-1H-isoindol-2-yl]piperidine-2,6-dione

Synonyms

ARV471; ARV 471; (S)-3-(5-(4-((1-(4-((1R,2S)-6-hydroxy-2-phenyl-1,2,3,4-tetrahydronaphthalen-1-yl)phenyl)piperidin-4-yl)methyl)piperazin-1-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; 2,6-Piperidinedione, 3-[1,3-dihydro-1-oxo-5-[4-[[1-[4-[(1R,2S)-1,2,3,4-tetrahydro-6-hydroxy-2-phenyl-1-naphthalenyl]phenyl]-4-piperidinyl]methyl]-1-piperazinyl]-2H-isoindol-2-yl]-, (3S)-; Vepdegestrant; (3S)-3-[1,3-Dihydro-1-oxo-5-[4-[[1-[4-[(1R,2S)-1,2,3,4-tetrahydro-6-hydroxy-2-phenyl-1-naphthalenyl]phenyl]-4-piperidinyl]methyl]-1-piperazinyl]-2H-isoindol-2-yl]-2,6-piperidinedione

Density

1.275±0.06 g/cm3

InChI Key

TZZDVPMABRWKIZ-XMOGEVODSA-N

InChI

InChI=1S/C45H49N5O4/c51-37-12-15-39-33(27-37)8-13-38(31-4-2-1-3-5-31)43(39)32-6-9-35(10-7-32)48-20-18-30(19-21-48)28-47-22-24-49(25-23-47)36-11-14-40-34(26-36)29-50(45(40)54)41-16-17-42(52)46-44(41)53/h1-7,9-12,14-15,26-27,30,38,41,43,51H,8,13,16-25,28-29H2,(H,46,52,53)/t38-,41+,43+/m1/s1

SMILES

C1CC2=C(C=CC(=C2)O)C(C1C3=CC=CC=C3)C4=CC=C(C=C4)N5CCC(CC5)CN6CCN(CC6)C7=CC8=C(C=C7)C(=O)N(C8)C9CCC(=O)NC9=O

Mechanism

Target: Targets estrogen receptor alpha (ERα) for experimental targeted protein degradation studies.

Binding Site: Binds the ERα ligand-binding domain and cereblon thalidomide-binding pocket to support productive ternary complex formation.

Mechanism of Action: ARV-471 is designed for use in PROTAC or targeted protein degradation experiments directed toward estrogen receptor alpha (ERα). The bifunctional molecule links a target-recognition element to cereblon, promoting proximity between the protein of interest and ubiquitination machinery. Productive ternary-complex formation can drive polyubiquitination and proteasome-dependent target depletion, allowing researchers to compare pharmacological inhibition with protein removal. It is suitable for evaluating degradation potency, kinetics, pathway selectivity, and downstream signaling consequences in engineered or disease-relevant cellular models.

Applications

• PROTAC-Mediated Estrogen Receptor Degradation: ARV-471 is a potent PROTAC designed to selectively degrade the estrogen receptor (ER) in breast cancer cells. Its application in research focuses on elucidating the mechanisms of ER-driven oncogenesis and exploring alternative therapeutic strategies for ER-positive breast cancer models.

• Targeted Protein Degradation in Oncology: Utilizing ARV-471 enables researchers to investigate the broader implications of targeted protein degradation in cancer biology. This PROTAC serves as a tool to dissect the role of specific protein targets in tumor progression and resistance mechanisms, providing insights into novel cancer treatment paradigms.

• Mechanistic Studies of PROTAC Efficacy: ARV-471 is employed in preclinical studies to understand the dynamics of PROTAC-induced protein degradation. Researchers can assess the efficiency of ARV-471 in degrading its target within cellular environments, thereby contributing to the optimization of PROTAC design and function.

• Exploring PROTAC Selectivity and Specificity: ARV-471 aids in evaluating the selectivity and specificity of PROTACs in degrading intended protein targets. This application is crucial for advancing the development of next-generation PROTACs with improved therapeutic indices and reduced off-target effects.

1. Abstract P5-04-18: ARV-471, an oral estrogen receptor PROTAC degrader for breast cancer.

Flanagan, J.J., Qian, Y., Gough, S.M., Andreoli, M., Bookbinder, M., Cadelina, G., Bradley, J., Rousseau, E., Willard, R., Pizzano, J. and Crews, C.M., 2019. Cancer research, 79(4_Supplement), pp.P5-04.

ARV-471, an estrogen receptor (ER) alpha PROTAC, is a hetero-bifunctional molecule that facilitates the interactions between estrogen receptor alpha and an intracellular E3 ligase complex, leading to the ubiquitylation and subsequent degradation of estrogen receptors via the proteasome. ARV-471 robustly degrades ER in ER-positive breast cancer cell lines with a half-maximal degradation concentration (DC50) of ˜ 2 nM. PROTAC-mediated ER degradation decreases the expression of classically-regulated ER-target genes (PR, GREB1, TFF) and inhibits cell proliferation of ER-dependent cell lines (MCF7, T47D). Additionally, ARV-471 degrades clinically-relevant ESR1 variants (Y537S and D538G) and inhibits growth of cell lines expressing those variants. In an immature rat uterotrophic model, ARV-471 degrades rat uterine ER and demonstrates no agonist activity. Daily, oral-administration of single agent ARV-471 (3, 10, and 30 mpk) leads to significant tumor volume regressions of estradiol-dependent MCF7 xenografts and concomitant tumor ER protein reductions of >90% at study termination. Moreover, when a CDK4/6 inhibitor is combined with ARV-471 in the MCF7 model, even more pronounced tumor growth inhibition is observed (˜130% TGI), accompanied by significant reductions in ER protein levels. In an ESR1 Y537S, hormone-independent patient-derived xenograft model, ARV-471 at 10 mpk completely inhibited growth and also reduced mutant ER protein levels. Taken together, the preclinical data of ARV-471 supports its continued development as a best-in-class oral ER PROTAC-degrader.

What is the melting point of it?

The melting point of ARV-471 is 180-182 °C.

31/7/2020

What is the stability of ARV-471 at room temperature and in storage?

ARV-471 is stable at room temperature and in storage for up to 2 years.

25/10/2021

Stock concentration: *

Desired final volume: *

Desired concentration: *

* Our calculator is based on the following equation:
Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
It is commonly abbreviated as: C₁V₁ = C₂V₂