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Chemical Structure| 664969-54-4 Chemical Structure| 664969-54-4

Structure of LF3
CAS No.: 664969-54-4

Chemical Structure| 664969-54-4

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LF3 is an inhibitor of canonical wnt signaling pathway with IC50 of less than 2 μM. It can disrupt the interaction between β-catenin and TCF4.

4.5 *For Research Use Only! Not for Human Use. We Do Not Sell to Patients.

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Product Citations

Product Citations

Gao, Yue ; Fan, Shicheng ; Zhao, Pengfei ; Li, Huilin ; Cai, Chenghui ; Li, Xuan , et al.

Abstract: Liver fibrosis can be characterized by the over-deposition of extracellular matrix (ECM). It has been reported that β-catenin/TCF4 interaction was enhanced in bile duct ligation (BDL) model, which implicated the critical role of β-catenin/TCF4 interaction during the progression of fibrosis. However, whether inhibiting β-catenin/TCF4 signaling attenuates liver fibrosis remains unknown. In the current study, we used ICG-001, an inhibitor that disrupts the interaction between CREB binding protein (CBP) and β-catenin, to inhibit β-catenin/TCF4 transcriptional activity. We also used LF3, a small molecule antagonist, to inhibit β-catenin/TCF4 interaction. The antifibrotic effect of ICG-001 and LF3 was assessed on BDL-induced liver fibrosis model. The results indicated both ICG-001 and LF3 significantly reduced the positive staining area of Sirius Red and α-SMA. The protein expression levels of α-SMA, Collagen Ⅰ and CD31 were also significantly downregulated in BDL + ICG-001 and BDL + LF3 groups. Besides, ICG-001 and LF3 promoted portal angiogenesis and inhibited sinusoids capillarization in fibrotic livers. For mechanistic study, we measured the level of leukocyte cell-derived chemotaxin 2 (LECT2), a direct target of β-catenin/TCF4, which was recently reported to participate in hepatic fibrosis by regulating angiogenesis. The results showed that both ICG-001 and LF3 reduced LECT2 expression in BDL mice. LF3 also downregulated pSer 675 β-catenin and nuclear β-catenin. In conclusion, this study demonstrated that inhibiting β-catenin/TCF4 signaling by ICG-001 or LF3 mitigated liver fibrosis by downregulating LECT2, promoting portal angiogenesis and inhibiting sinusoids capillarization, which provided new evidence that β-catenin/TCF4 signaling might be a target for the treatment of liver fibrosis.

Keywords: Leukocyte cell-derived chemotaxin 2 ; β-catenin/TCF4 signaling ; Liver fibrosis ; Angiogenesis ; Bile duct ligation

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Product Details of LF3

CAS No. :664969-54-4
Formula : C20H24N4O2S2
M.W : 416.56
SMILES Code : S=C(N1CCN(C/C=C/C2=CC=CC=C2)CC1)NC3=CC=C(S(=O)(N)=O)C=C3
English Name :4-(3-Phenylallyl)-N-(4-sulfamoylphenyl)piperazine-1-carbothioamide
MDL No. :MFCD03352482
InChI Key :ZUQIFHLBPBLRRM-QPJJXVBHSA-N
Pubchem ID :1213452

Safety of LF3

Isoform Comparison

Biological Activity

In Vitro:

Cell Line
Concentration Treated Time Description References
HGC-27 cells 0, 3.3, 10 µM Inhibited the expression of CD44, NANOG, and SOX9 Commun Biol. 2024 May 7;7(1):545.
HEK 293 cells 10 µM 48 hours LF3 significantly increased SCN5A promoter activity and prevented β-catenin's suppressive effect on SCN5A promoter activity. J Mol Cell Cardiol. 2019 Oct;135:90-96.
HL-1 cardiomyocytes 10 µM 72 hours LF3 significantly increased the expression level of Na V1.5 but did not affect the expression of β-catenin and TCF4. J Mol Cell Cardiol. 2019 Oct;135:90-96.

Clinical Trial:

NCT Number Conditions Phases Recruitment Completion Date Locations
NCT02683616 Obstructive Sleep Apnea ... More >> Fatty Acid Metabolism Continuous Positive Airway Pressure Less << Not Applicable Recruiting December 2019 Czechia ... More >> FN Kralovske Vinohrady Recruiting Prague, Czechia, 10034 Contact: Jan Polak, MD, PhD    +420267162710    jan.polak@lf3.cuni.cz    Contact: Jan Gojda, MD, PhD    +420267168144    jan.gojda@lf3.cuni.cz Less <<
NCT03710850 Insulin Resistance ... More >> Microbiome Less << Not Applicable Recruiting December 31, 2021 Czechia ... More >> University Hospital Kralovske Vinohrady Recruiting Prague, Czechia, 10084 Contact: Jana Potočková    +420267163031    klinicka.fyziologie@lf3.cuni.cz Less <<
NCT03386461 Metabolism Disorder ... More >> Adiposity Inflammatory Response Less << Not Applicable Recruiting December 2019 Czechia ... More >> Third Faculty of Medicine, Charles University Recruiting Prague, Czechia, 100 00 Contact: Michaela Siklova, PhD    +420 267 102 211    michaela.siklova@lf3.cuni.cz    Contact: Lenka Rossmeislova, PhD    +420 267 102 211    lenka.rossmeislova@lf3.cuni.cz    Principal Investigator: Michaela Siklova, PhD          Sub-Investigator: Martin Rossmeisl, PhD          Sub-Investigator: Vladimir Stich, prof. MUDr. Less <<
NCT03155412 - Recruiting December 2018 Czechia ... More >> Third Faculty of Medicine, Charles University Recruiting Prague, Czechia, 100 00 Contact: Michaela Siklova, PhD    +420 267 102 211    michaela.siklova@lf3.cuni.cz    Principal Investigator: Vladimir Stich, prof Less <<

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.40mL

0.48mL

0.24mL

12.00mL

2.40mL

1.20mL

24.01mL

4.80mL

2.40mL

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