Name: 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
Brand: BOC Sciences
Rating: 5 (1 reviews)

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IUPACName

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

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]-

Density

1.275±0.06 g/cm3

InChI Key

TZZDVPMABRWKIZ-MFTLXVFQSA-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: This compound, vepdegestrant, selectively targets estrogen receptor alpha, encoded by ESR1.

Binding site: Its ER ligand binds the estrogen receptor ligand-binding domain.

Mechanism of action: Vepdegestrant, also known as ARV-471, is a heterobifunctional PROTAC estrogen receptor degrader composed of an ERα-binding element joined to an E3 ligase recognition moiety. By bringing ERα into proximity with intracellular ubiquitin ligase machinery, the compound promotes receptor ubiquitination and proteasome-mediated depletion. In research applications, this mechanism supports analysis of ERα dependence, ESR1-mutant receptor biology, transcriptional pathway suppression, and differences between receptor antagonism and complete protein degradation. The molecule is especially relevant for studying degradation-driven modulation of hormone receptor signaling in ER-positive cellular models.

Applications

• PROTAC-Mediated Targeted Degradation: This compound serves as a versatile tool in the study of targeted protein degradation, enabling researchers to selectively degrade proteins of interest. By facilitating the recruitment of E3 ligases to target proteins, it promotes ubiquitination and subsequent proteasomal degradation, offering insights into protein function and regulation.

• Protein Interaction Studies via PROTAC: The compound is instrumental in dissecting protein-protein interactions within cellular environments. It allows for the selective degradation of one interaction partner, helping to elucidate the functional consequences and biological significance of specific protein complexes.

• Pathway Analysis Using PROTACs: Researchers utilize this PROTAC to investigate cellular pathways by targeting key regulatory proteins for degradation. This approach aids in understanding the dynamics of signaling networks and the role of specific proteins in maintaining cellular homeostasis.

• PROTAC-Based Mechanistic Studies: By employing this compound, scientists can perform detailed mechanistic studies to explore the degradation kinetics and specificity of targeted proteins. Such investigations are crucial for optimizing PROTAC design and enhancing their efficacy in protein degradation applications.

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 functional group of 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?

The functional group of 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 is amide. An amide is a functional group with the formula R-C(O)-NR'R''. It is formed by the reaction of an amine with a carboxylic acid, with the loss of water. Amides are found in a wide variety of natural and synthetic compounds, including proteins, peptides, and drugs. In the case of 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, the amide functional group is present in the 2,6-piperidinedione ring. The amide functional group is responsible for the water solubility of this compound.

5/7/2019

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* 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