Name: SJF 1521
Brand: BOC Sciences
Rating: 5 (1 reviews)

Size

Price

Stock

Quantity

$--

In stock

Purity

≥95%

Solubility

Soluble in DMSO

Appearance

Pale Green/Yellow Solid

Storage

Store at 2-8°C for short term (days to weeks) or -20°C for long term (months to years)

IUPACName

(2S,4R)-1-[(2S)-2-[[2-[2-[2-[2-[4-[4-[3-chloro-4-[(3-fluorophenyl)methoxy]anilino]quinazolin-6-yl]phenoxy]ethoxy]ethoxy]ethoxy]acetyl]amino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide

Synonyms

N-({2-[2-(2-{4-[4-({3-Chloro-4-[(3-fluorobenzyl)oxy]phenyl}amino)-6-quinazolinyl]phenoxy}ethoxy)ethoxy]ethoxy}acetyl)-3-methyl-L-valyl-(4R)-4-hydroxy-N-[4-(4-methyl-1,3-thiazol-5-yl)benzyl]-L-prolinamide; (2S,4R)-1-((S)-2-(tert-Butyl)-14-(4-(4-((3-chloro-4-((3-fluorobenzyl)oxy)phenyl)amino)quinazolin-6-yl)phenoxy)-4-oxo-6,9,12-trioxa-3-azatetradecanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide; L-Prolinamide, N-[2-[2-[2-[2-[4-[4-[[3-chloro-4-[(3-fluorophenyl)methoxy]phenyl]amino]-6-quinazolinyl]phenoxy]ethoxy]ethoxy]ethoxy]acetyl]-3-methyl-L-valyl-4-hydroxy-N-[[4-(4-methyl-5-thiazolyl)phenyl]methyl]-, (4R)-; EGFR PROTAC

Boiling Point

1160.1±65.0°C at 760 Torr

Density

1.314±0.06 g/cm3

InChI Key

XZNORRXEBCTXPB-KHBXAZQSSA-N

InChI

InChI=1S/C57H61ClFN7O9S/c1-36-52(76-35-63-36)40-10-8-37(9-11-40)30-60-55(69)49-29-44(67)31-66(49)56(70)53(57(2,3)4)65-51(68)33-73-23-22-71-20-21-72-24-25-74-45-16-12-39(13-17-45)41-14-18-48-46(27-41)54(62-34-61-48)64-43-15-19-50(47(58)28-43)75-32-38-6-5-7-42(59)26-38/h5-19,26-28,34-35,44,49,53,67H,20-25,29-33H2,1-4H3,(H,60,69)(H,65,68)(H,61,62,64)/t44-,49+,53-/m1/s1

SMILES

CC1=C(SC=N1)C2=CC=C(C=C2)CNC(=O)C3CC(CN3C(=O)C(C(C)(C)C)NC(=O)COCCOCCOCCOC4=CC=C(C=C4)C5=CC6=C(C=C5)N=CN=C6NC7=CC(=C(C=C7)OCC8=CC(=CC=C8)F)Cl)O

Mechanism

Target: SJF 1521 selectively targets EGFR, including mutant EGFR forms, while sparing HER2.

Binding site: Its lapatinib-derived ligand binds the ATP pocket of the EGFR kinase domain.

Mechanism of action: SJF 1521 is a VHL-recruiting EGFR PROTAC composed of a lapatinib-based EGFR ligand connected to a von Hippel-Lindau E3 ligase ligand. This design promotes selective ternary-complex formation between EGFR and VHL, leading to EGFR ubiquitination and proteasome-mediated degradation. Reported studies indicate EGFR degradation in OVCAR8 cells with selectivity over HER2, making SJF 1521 useful for dissecting EGFR-specific receptor biology. It supports experiments evaluating mutant and wild-type EGFR depletion, downstream signaling changes, receptor selectivity, and differences between lapatinib-like inhibition and degradation-based target removal.

Applications

• PROTAC-Mediated Kinase Degradation: SJF 1521 is a potent PROTAC designed for the selective degradation of specific kinases, facilitating the exploration of kinase-dependent signaling pathways. This application is crucial for elucidating kinase function and identifying potential therapeutic targets in cancer and other diseases.

• Targeted Protein Knockdown Studies: Utilizing SJF 1521 in targeted protein degradation experiments allows researchers to achieve precise knockdown of proteins of interest. This approach aids in validating protein roles in cellular processes and understanding the consequences of protein loss on cellular function.

• Mechanistic Insights into Protein Degradation: SJF 1521 serves as a valuable tool for investigating the mechanisms underlying PROTAC-induced protein degradation. By examining the ubiquitin-proteasome pathway engagement, researchers can gain insights into the efficiency and selectivity of the degradation process.

• Functional Genomics Research: The application of SJF 1521 in functional genomics enables the study of gene function through targeted protein degradation. This strategy supports the identification of essential genes and pathways, contributing to the development of novel therapeutic strategies.

1. The advantages of targeted protein degradation over inhibition: an RTK case study.

Burslem, G.M., Smith, B.E., Lai, A.C., Jaime-Figueroa, S., McQuaid, D.C., Bondeson, D.P., Toure, M., Dong, H., Qian, Y., Wang, J. and Crew, A.P., 2018. Cell chemical biology, 25(1), pp.67-77.

Proteolysis targeting chimera (PROTAC) technology has emerged over the last two decades as a powerful tool for targeted degradation of endogenous proteins. Herein we describe the development of PROTACs for receptor tyrosine kinases, a protein family yet to be targeted for induced protein degradation. The use of VHL-recruiting PROTACs against this protein family reveals several advantages of degradation over inhibition alone: direct comparisons of fully functional, target-degrading PROTACs with target-inhibiting variants that contain an inactivated E3 ligase-recruiting ligand show that degradation leads to more potent inhibition of cell proliferation and a more durable and sustained downstream signaling response, and thus addresses the kinome rewiring challenge seen with many receptor tyrosine kinase inhibitors. Combined, these findings demonstrate the ability to target receptor tyrosine kinases for degradation using the PROTAC technology and outline the advantages of this degradation-based approach.

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