Name: SJF-1528
Brand: BOC Sciences
Rating: 5 (1 reviews)

Size

Price

Stock

Quantity

$--

In stock

Purity

≥95%

Solubility

Soluble in DMSO

Appearance

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

Synonyms

(2S,4R)-1-((S)-2-(2-(2-(2-(4-(4-((3-chloro-4-((3-fluorobenzyl)oxy)phenyl)amino)quinazolin-6-yl)phenoxy)ethoxy)ethoxy)acetamido)-3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide; N-{[2-(2-{4-[4-({3-Chloro-4-[(3-fluorobenzyl)oxy]phenyl}amino)-6-quinazolinyl]phenoxy}ethoxy)ethoxy]acetyl}-3-methyl-L-valyl-(4R)-4-hydroxy-N-[4-(4-methyl-1,3-thiazol-5-yl)benzyl]-L-prolinamide; L-Prolinamide, N-[2-[2-[2-[4-[4-[[3-chloro-4-[(3-fluorophenyl)methoxy]phenyl]amino]-6-quinazolinyl]phenoxy]ethoxy]ethoxy]acetyl]-3-methyl-L-valyl-4-hydroxy-N-[[4-(4-methyl-5-thiazolyl)phenyl]methyl]-, (4R)-; SJF 1528; SJF1528

Boiling Point

1141.7±65.0°C at 760 Torr

Density

1.324±0.06 g/cm3

InChI Key

ZSCOIFSUFMYZEZ-YSWDPXALSA-N

InChI

InChI=1S/C55H57ClFN7O8S/c1-34-50(73-33-61-34)38-10-8-35(9-11-38)28-58-53(67)47-27-42(65)29-64(47)54(68)51(55(2,3)4)63-49(66)31-70-21-20-69-22-23-71-43-16-12-37(13-17-43)39-14-18-46-44(25-39)52(60-32-59-46)62-41-15-19-48(45(56)26-41)72-30-36-6-5-7-40(57)24-36/h5-19,24-26,32-33,42,47,51,65H,20-23,27-31H2,1-4H3,(H,58,67)(H,63,66)(H,59,60,62)/t42-,47+,51-/m1/s1

SMILES

CC1=C(SC=N1)C2=CC=C(C=C2)CNC(=O)C3CC(CN3C(=O)C(C(C)(C)C)NC(=O)COCCOCCOC4=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-1528 targets EGFR and also induces degradation of HER2.

Binding site: Its lapatinib-derived ligand binds ErbB-family ATP-competitive kinase pockets.

Mechanism of action: SJF-1528 is a lapatinib-based VHL-recruiting PROTAC that induces degradation of EGFR and HER2. It contains an ErbB-family kinase ligand joined to a von Hippel-Lindau ligand through a linker, enabling recruitment of receptor kinases to VHL-dependent ubiquitination machinery. Reported activity includes degradation of wild-type EGFR in OVCAR8 cells and exon 20 insertion mutant EGFR in HeLa cells, with additional HER2 degradation. SJF-1528 is useful for comparative studies of EGFR versus HER2 degradation, receptor signaling suppression, mutant EGFR depletion, and ErbB pathway dependency.

Applications

• PROTAC Development: SJF-1528 serves as a valuable tool in the development of novel PROTAC molecules, facilitating the study of targeted protein degradation mechanisms. Researchers can utilize this compound to explore the efficacy and specificity of protein knockdown, advancing the design of next-generation degraders.

• Targeted Degradation Research: By employing SJF-1528, scientists can investigate the targeted degradation of specific proteins, providing insights into protein homeostasis and cellular processes. This application aids in understanding the therapeutic potential of protein degradation strategies in various diseases.

• Mechanistic Studies: SJF-1528 enables detailed mechanistic studies of PROTAC-induced ubiquitination and subsequent proteasomal degradation. Researchers can dissect the molecular interactions and pathways involved, enhancing knowledge of how PROTACs achieve selective protein elimination.

• Cellular Pathway Analysis: Utilizing SJF-1528 in cellular models allows for the analysis of protein degradation impacts on signaling pathways. This application helps elucidate the role of specific proteins in cellular physiology and disease, offering potential targets for therapeutic intervention.

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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Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
It is commonly abbreviated as: C₁V₁ = C₂V₂