Name: FC-11
Brand: BOC Sciences
Rating: 5 (1 reviews)

Size

Price

Stock

Quantity

$--

In stock

Purity

≥95%

Solubility

Soluble in DMSO

Appearance

Yellow Solid

Storage

Store at -20°C

IUPACName

1-[2-[2-[2-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]ethoxy]ethoxy]ethyl]-N-[4-[[4-[[2-[methyl(methylsulfonyl)amino]pyridin-3-yl]methylamino]-5-(trifluoromethyl)pyrimidin-2-yl]amino]phenyl]triazole-4-carboxamide

Synonyms

1-(2-(2-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)ethoxy)ethoxy)ethyl)-N-(4-((4-(((2-(N-methylmethylsulfonamido)pyridin-3-yl)methyl)amino)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)-1H-1,2,3-triazole-4-carboxamide; 1H-1,2,3-Triazole-4-carboxamide, 1-[2-[2-[2-[[2-(2,6-dioxo-3-piperidinyl)-2,3-dihydro-1,3-dioxo-1H-isoindol-4-yl]amino]ethoxy]ethoxy]ethyl]-N-[4-[[4-[[[2-[methyl(methylsulfonyl)amino]-3-pyridinyl]methyl]amino]-5-(trifluoromethyl)-2-pyrimidinyl]amino]phenyl]-; 1-[2-[2-[2-[[2-(2,6-Dioxo-3-piperidinyl)-2,3-dihydro-1,3-dioxo-1H-isoindol-4-yl]amino]ethoxy]ethoxy]ethyl]-N-[4-[[4-[[[2-[methyl(methylsulfonyl)amino]-3-pyridinyl]methyl]amino]-5-(trifluoromethyl)-2-pyrimidinyl]amino]phenyl]-1H-1,2,3-triazole-4-carboxamide

Density

1.57±0.1 g/cm3

InChI Key

RZKZQCHSKWKOAJ-UHFFFAOYSA-N

InChI

InChI=1S/C41H42F3N13O9S/c1-55(67(2,63)64)35-24(5-4-14-46-35)21-47-34-28(41(42,43)44)22-48-40(52-34)50-26-10-8-25(9-11-26)49-36(59)30-23-56(54-53-30)16-18-66-20-19-65-17-15-45-29-7-3-6-27-33(29)39(62)57(38(27)61)31-12-13-32(58)51-37(31)60/h3-11,14,22-23,31,45H,12-13,15-21H2,1-2H3,(H,49,59)(H,51,58,60)(H2,47,48,50,52)

SMILES

CN(C1=NC=CC=C1CNC1=NC(NC2=CC=C(NC(=O)C3=CN(CCOCCOCCNC4=CC=CC5=C4C(=O)N(C4CCC(=O)NC4=O)C5=O)N=N3)C=C2)=NC=C1C(F)(F)F)S(C)(=O)=O

Mechanism

Target: FC-11 selectively targets focal adhesion kinase, also known as FAK or PTK2.

Binding site: Its PF562271-derived ligand binds the ATP pocket of the FAK kinase domain.

Mechanism of action: FC-11 is a highly potent CRBN-recruiting FAK PROTAC composed of the FAK inhibitor PF562271, a linker, and the cereblon ligand pomalidomide. This bifunctional structure recruits FAK to CRL4CRBN ubiquitin ligase machinery, promoting FAK ubiquitination and proteasome-dependent degradation. Because FAK functions both as a kinase and adhesion-associated scaffold, FC-11 enables experimental distinction between catalytic inhibition and complete protein depletion. It is useful for studying focal adhesion signaling, migration, survival pathways, degradation potency, and cellular phenotypes caused by sustained FAK removal.

Applications

• PROTAC-Mediated Kinase Degradation: FC-11 is utilized in research to selectively degrade specific kinase proteins, enabling the study of kinase signaling pathways. By targeting these proteins for degradation, researchers can dissect cellular processes and elucidate the role of kinases in various diseases, offering insights into potential therapeutic targets.

• Targeted Degradation in Cancer Research: FC-11 facilitates the investigation of oncogenic protein degradation in cancer cells. By promoting the selective degradation of proteins implicated in tumor growth, this PROTAC aids in understanding the molecular mechanisms of cancer progression and the identification of novel intervention strategies.

• Protein Homeostasis Regulation: FC-11 is employed in studies focusing on the regulation of protein homeostasis through targeted degradation. By leveraging the PROTAC mechanism, researchers can explore how the controlled degradation of specific proteins affects cellular equilibrium and contributes to disease pathology.

• Advancing Drug Discovery: FC-11 serves as a tool in drug discovery research, allowing scientists to evaluate the potential of targeted protein degradation as a therapeutic strategy. This application supports the development of innovative treatments by providing insights into the degradation pathways of disease-relevant proteins.

1. FAK-targeting PROTAC as a chemical tool for the investigation of non-enzymatic FAK function in mice.

Gao, H., Zheng, C., Du, J., Wu, Y., Sun, Y., Han, C., Kee, K. and Rao, Y., 2020. Protein & cell, 11(7), pp.534-539.

Animal models, most commonly mice, that lack a protein of interest play an important role in phenotypic and functional studies of a target gene, allowing researchers to answer various biological questions (Chaible et al., 2010). At present, a variety of tools act at the DNA or RNA level to enable researchers to model gene function (and thus protein) deficiency, including nucleic acid-based RNA interference (Elbashir et al., 2001), antisense oligonucleotides (Schoch and Miller, 2017), and genome editing-based CRISPR-Cas9 (Doudna and Charpentier, 2014) strategies. However, challenges remain. RNA and DNA-based technologies lack exquisite temporal control of the target gene at specified time points in an organism's development, and they fail to realize acute and reversible target gene function (Chan, 2013). These shortcomings have garnered widespread concern in both fundamental research and drug development. Furthermore, gene knockout will often lead to embryonic lethality, precluding the study of post-embryonic pathophysiological functions of target genes and proteins of interest (Dhanjal et al., 2017).

2. Design, synthesis, and evaluation of highly potent FAK-targeting PROTACs.

Gao, H., Wu, Y., Sun, Y., Yang, Y., Zhou, G. and Rao, Y., 2019. ACS medicinal chemistry letters, 11(10), pp.1855-1862.

Focal adhesion kinase (FAK), a cytoplasmic protein tyrosine kinase, exerts kinase-dependent enzymatic functions and kinase-independent scaffolding functions, both of which are crucial in cancer development, early embryonic development, and reproduction. However, previous efforts for FAK blocking mainly focus on kinase inhibitors. Proteolysis targeting chimeras (PROTACs) are heterobifunctional molecules that allow direct post-translational knockdown of proteins via ubiquitination of a target protein by E3 ubiquitin ligase and subsequent proteasomal degradation. Here, we designed and synthesized a FAK PROTAC library with FAK inhibitor (PF562271 or VS6063) and CRBN E3 ligand. A novel FAK-targeting PROTAC, FC-11, showed a rapid and reversible FAK degradation with a picomolar of DC50 in various cell lines in vitro, which imply that FAK-PROTACs could be useful as expand tools for studying functions of FAK in biological system and as potential therapeutic agents.

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