Name: BI-3663
Brand: BOC Sciences
Rating: 5 (1 reviews)

Size

Price

Stock

Quantity

$--

In stock

Purity

≥95%

Solubility

Soluble in DMSO

Appearance

Solid Powder

Storage

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

Shipping

Room temperature in continental US; may vary elsewhere

IUPACName

N-[2-[2-[2-[3-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]-3-oxopropoxy]ethoxy]ethoxy]ethyl]-3-methoxy-4-[[4-[(3-oxo-1,2-dihydroinden-4-yl)oxy]-5-(trifluoromethyl)pyrimidin-2-yl]amino]benzamide

Synonyms

N-(2-(2-(2-(3-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)-3-oxopropoxy)ethoxy)ethoxy)ethyl)-3-methoxy-4-((4-((3-oxo-2,3-dihydro-1H-inden-4-yl)oxy)-5-(trifluoromethyl)pyrimidin-2-yl)amino)benzamide; BI 3663; BI3663; Benzamide, 4-[[4-[(2,3-dihydro-3-oxo-1H-inden-4-yl)oxy]-5-(trifluoromethyl)-2-pyrimidinyl]amino]-N-[2-[2-[2-[3-[[2-(2,6-dioxo-3-piperidinyl)-2,3-dihydro-1,3-dioxo-1H-isoindol-4-yl]amino]-3-oxopropoxy]ethoxy]ethoxy]ethyl]-3-methoxy-; 4-[[4-[(2,3-Dihydro-3-oxo-1H-inden-4-yl)oxy]-5-(trifluoromethyl)-2-pyrimidinyl]amino]-N-[2-[2-[2-[3-[[2-(2,6-dioxo-3-piperidinyl)-2,3-dihydro-1,3-dioxo-1H-isoindol-4-yl]amino]-3-oxopropoxy]ethoxy]ethoxy]ethyl]-3-methoxybenzamide

Density

1.456±0.06 g/cm3

InChI Key

ADTXLFJKQHYGPM-UHFFFAOYSA-N

InChI

InChI=1S/C44H42F3N7O12/c1-62-33-22-25(8-10-28(33)51-43-49-23-27(44(45,46)47)40(53-43)66-32-7-2-4-24-9-12-31(55)36(24)32)38(58)48-15-17-64-19-21-65-20-18-63-16-14-35(57)50-29-6-3-5-26-37(29)42(61)54(41(26)60)30-11-13-34(56)52-39(30)59/h2-8,10,22-23,30H,9,11-21H2,1H3,(H,48,58)(H,50,57)(H,49,51,53)(H,52,56,59)

SMILES

COC1=C(C=CC(=C1)C(=O)NCCOCCOCCOCCC(=O)NC2=CC=CC3=C2C(=O)N(C3=O)C4CCC(=O)NC4=O)NC5=NC=C(C(=N5)OC6=CC=CC7=C6C(=O)CC7)C(F)(F)F

Mechanism

Target: BI-3663 selectively targets focal adhesion kinase, also called PTK2 or FAK.

Binding site: Its BI-4464-derived ligand binds the ATP pocket of FAK kinase domain.

Mechanism of action: BI-3663 is a cereblon-recruiting PTK2/FAK PROTAC composed of the FAK inhibitor BI-4464 linked to a pomalidomide-derived CRBN ligand. By recruiting PTK2 to CRL4CRBN ubiquitin ligase machinery, BI-3663 promotes target ubiquitination and proteasome-dependent degradation at low nanomolar concentrations in reported cellular systems. This degradation mechanism is useful for studying FAK functions that extend beyond catalytic activity, including adhesion-associated scaffold roles, migration signaling, survival pathway regulation, and downstream phenotypes caused by sustained PTK2 protein depletion rather than reversible kinase inhibition alone.

Applications

• PROTAC-Mediated Targeted Degradation: BI-3663 is utilized in research to selectively degrade disease-relevant proteins through the ubiquitin-proteasome system. By harnessing this mechanism, researchers can study the direct effects of protein depletion on cellular pathways, providing insights into protein function and potential therapeutic targets.

• Investigating Protein-Protein Interactions: BI-3663 aids in the exploration of transient protein-protein interactions by degrading the target protein, allowing scientists to delineate interaction networks and understand their roles in cellular processes, thereby advancing the understanding of complex biological systems.

• Functional Genomics Studies: Through the application of BI-3663, researchers can perform functional genomics studies by systematically degrading specific proteins, enabling the identification of crucial proteins involved in disease pathways and facilitating the development of novel therapeutic strategies.

• Drug Discovery Research: BI-3663 serves as a valuable tool in drug discovery by allowing the evaluation of protein degradation as a therapeutic approach. This facilitates the identification of new drug targets and the development of compounds that can modulate protein levels in disease models.

1. Highly selective PTK2 proteolysis targeting chimeras to probe focal adhesion kinase scaffolding functions.

Popow, J., Arnhof, H., Bader, G., Berger, H., Ciulli, A., Covini, D., Dank, C., Gmaschitz, T., Greb, P., Karolyi-Özguer, J. and Koegl, M., 2019. Journal of Medicinal Chemistry, 62(5), pp.2508-2520.

Focal adhesion tyrosine kinase (PTK2) is often overexpressed in human hepatocellular carcinoma (HCC), and several reports have linked PTK2 depletion and/or pharmacological inhibition to reduced tumorigenicity. However, the clinical relevance of targeting PTK2 still remains to be proven. Here, we present two highly selective and functional PTK2 proteolysis-targeting chimeras utilizing von Hippel-Lindau and cereblon ligands to hijack E3 ligases for PTK2 degradation. BI-3663 (cereblon-based) degrades PTK2 with a median DC50 of 30 nM to >80% across a panel of 11 HCC cell lines. Despite effective PTK2 degradation, these compounds did not phenocopy the reported antiproliferative effects of PTK2 depletion in any of the cell lines tested. By disclosing these compounds, we hope to provide valuable tools for the study of PTK2 degradation across different biological systems.

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