Name: SJF620 hydrochloride
Brand: BOC Sciences
Rating: 5 (1 reviews)

Size

Price

Stock

Quantity

$--

In stock

Purity

≥99%

Solubility

Soluble in DMSO

Storage

Store at -20°C

IUPACName

3-[6-[2-[2-[2-[4-[4-amino-3-(4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidin-1-yl]ethoxy]ethoxy]ethoxy]-3-oxo-1H-isoindol-2-yl]piperidine-2,6-dione;hydrochloride

Synonyms

3-(5-{2-[2-(2-{4-[4-Amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]-1-piperidinyl}ethoxy)ethoxy]ethoxy}-1-oxo-1,3-dihydro-2H-isoindol-2-yl)-2,6-piperidinedione hydrochloride (1:1); 2,6-Piperidinedione, 3-[5-[2-[2-[2-[4-[4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]-1-piperidinyl]ethoxy]ethoxy]ethoxy]-1,3-dihydro-1-oxo-2H-isoindol-2-yl]-, hydrochloride (1:1)

InChI Key

RLEKBKXQGCJLQZ-UHFFFAOYSA-N

InChI

InChI=1S/C41H44N8O7.ClH/c42-38-36-37(27-6-8-31(9-7-27)56-30-4-2-1-3-5-30)46-49(39(36)44-26-43-38)29-14-16-47(17-15-29)18-19-53-20-21-54-22-23-55-32-10-11-33-28(24-32)25-48(41(33)52)34-12-13-35(50)45-40(34)51;/h1-11,24,26,29,34H,12-23,25H2,(H2,42,43,44)(H,45,50,51);1H

SMILES

C1CC(=O)NC(=O)C1N2CC3=C(C2=O)C=CC(=C3)OCCOCCOCCN4CCC(CC4)N5C6=NC=NC(=C6C(=N5)C7=CC=C(C=C7)OC8=CC=CC=C8)N.Cl

Mechanism

Target: SJF620 hydrochloride selectively targets Bruton’s tyrosine kinase for CRBN-mediated degradation.

Binding site: Its BTK ligand binds the ATP-binding catalytic pocket of BTK.

Mechanism of action: SJF620 hydrochloride is the hydrochloride salt form of a potent BTK-directed PROTAC composed of a BTK ligand linked to a lenalidomide-like cereblon recruiter. By simultaneously engaging BTK and CRL4CRBN, the compound drives ternary-complex formation, BTK ubiquitination, and proteasome-dependent degradation. This mechanism enables depletion of BTK protein rather than transient enzymatic inhibition, allowing investigation of kinase-dependent and scaffold-associated BTK functions. SJF620 hydrochloride is suitable for studying B-cell receptor signaling, degradation potency, downstream pathway suppression, and comparative effects of BTK inhibitors versus degraders.

Applications

• PROTAC-Mediated Targeted Degradation: SJF620 hydrochloride is utilized in research to investigate the degradation of specific proteins via the ubiquitin-proteasome system. By facilitating the recruitment of E3 ligases to target proteins, it enables the study of protein function and regulation through targeted degradation mechanisms.

• Protein-Protein Interaction Studies: This compound is instrumental in exploring the dynamics of protein-protein interactions involved in cellular pathways. By inducing selective protein degradation, researchers can dissect complex signaling networks and identify potential therapeutic targets.

• Drug Discovery and Development: SJF620 hydrochloride serves as a valuable tool in the discovery phase of drug development, allowing for the validation of novel targets through the mechanism of PROTAC-induced degradation, thereby accelerating the identification of viable drug candidates.

• Mechanistic Pathway Analysis: Researchers employ SJF620 hydrochloride to elucidate the roles of specific proteins within cellular pathways. Through PROTAC technology, it offers insights into mechanistic pathways by selectively degrading proteins of interest, thus enhancing the understanding of cellular processes.

1. Design, synthesis and biological evaluation of Proteolysis Targeting Chimeras (PROTACs) as a BTK degraders with improved pharmacokinetic properties.

Jaime-Figueroa, S., Buhimschi, A.D., Toure, M., Hines, J. and Crews, C.M., 2020. Bioorganic & medicinal chemistry letters, 30(3), p.126877.

A new series of Proteolysis Targeting Chimeras (PROTACs) targeting Bruton's Tyrosine Kinase (BTK) was synthesized, with the goal of improving the pharmacokinetic properties of our previously reported PROTAC, MT802. We recently described the ability of MT802 to induce degradation of both wild-type and C481S mutant BTK in immortalized cells and patient-derived B-lymphocytes. However, the pharmacokinetic properties of MT802 were not suitable for further in vivo development. Therefore, we undertook a systematic medicinal chemistry campaign to overcome this issue and made a series of PROTACs with structural modifications to the linker and E3-recruiting ligand; more specifically, the new PROTACs were synthesized with different von Hippel-Lindau (VHL) and cereblon (CRBN) ligands while keeping the BTK ligand and linker length constant. This approach resulted in an equally potent PROTAC, SJF620, with a significantly better pharmacokinetic profile than MT802. This compound may hold promise for further in vivo exploration of BTK degradation.

Good afternoon, dear team, could you please tell me the biological features of this compound? thank you.

PROTAC for BTK degradation: SJF620 hydrochloride is a PROTAC, meaning it acts as a bridge between BTK and the E3 ubiquitin ligase Cereblon. This triggers the ubiquitination and subsequent degradation of BTK by the proteasome. Potent and selective: SJF620 hydrochloride exhibits potent BTK degradation, with a DC50 (concentration needed to degrade 50% of BTK) of 7.9 nM. It also shows good selectivity for BTK over other proteins. Chemical structure: It features two ligands: one for binding to Cereblon and another for binding to BTK. These ligands are connected by a linker.

8/11/2016

Could you tell me its potential application, thanks.

SJF620 hydrochloride holds promise for treating various B-cell malignancies, such as leukemia and lymphoma, where BTK plays a crucial role. Additionally, it may have potential in autoimmune diseases and inflammatory conditions involving BTK signaling.

25/2/2022

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