Cell lines

Rat Epicardial Cells

Preparation method

The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.

Reaction Conditions

10 μM, 24 hours

Applications

The rat EMCs were treated with either ICG-001 or IQ1 and performed co-immunoprecipitation (co-IP) assays. Cells were treated with DMSO, ICG-001 or IQ1 for 24 hours. In the DMSO control treated cells, essentially all of the β-catenin was associated with CBP. Treatment with IQ1 had minimal effects on β-catenin coactivator usage. However, as anticipated, treatment with ICG-001 decreased the β-catenin/CBP interaction, while concomitantly increasing the β-catenin/p300 interaction.

Animal models

Female Sprague-Dawley rats

Dosage form

Subcutaneous injection, 50 mg/kg/day

Applications

The left coronary artery of the rats was permanently occluded via surgery to induce regional ischemic injury to the left ventricle. ICG-001 was administered to the rats beginning on the day of surgery for 10 days. Four weeks after surgery (20 days after the last ICG-001 treatment), left ventricular ejection fraction was assessed by angiography as an indicator of cardiac contractile function. ICG-001 significantly improved ejection fraction by 8.4% from 46.2±1.7% to 54.6±3.4% (P < 0.05). This data demonstrates that ICG-001 significantly improved cardiac contractile function after myocardial infarction in the rats.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

ICG001 is a small molecule inhibitor that targets Wnt/β-catenin pathway. It inhibits TCF/β-catenin mediated transcription by competing with β-catenin for CBP (CREB binding protein) but not p300 binding with an IC50 of 3 μM [1]. It can be used to specifically evaluate the role of CBP/beta-catenin association on WNT signaling and cell physiology.

ICG001 have been shown to selectively inhibit colon carcinoma cell lines (SW480 and HCT-116 cells) but not normal colonic epithelial cells (CCD-841Co). It is also efficacious in the Min mouse and nude mouse xenograft models of colon cancer [1]. ICG-001 is a potent inhibitor of GBM stem cells in culture. ICG001 selectively inhibits Wnt/beta-catenin/CREB binding protein (CBP) signaling to reverses pulmonary fibrosis and ameliorate experimental dermal fibrosis in experimental models [2,3]. ICG001 is currently in clinical trial for colon cancer and leukemias.

References:
[1]Emami KH, Nguyen C, Ma H, Kim DH, Jeong KW, Eguchi M, Moon RT, Teo JL, Kim HY, Moon SH, Ha JR, Kahn M. A small molecule inhibitor of beta-catenin/CREB-binding protein transcription. Proc Natl Acad Sci U S A. 2004 Aug 24;101(34):12682-7.
[2]Henderson WR Jr1, Chi EY, Ye X, Nguyen C, Tien YT, Zhou B, Borok Z, Knight DA, Kahn M. Inhibition of Wnt/beta-catenin/CREB binding protein (CBP) signaling reverses pulmonary fibrosis. Proc Natl Acad Sci U S A. 2010 Aug 10;107(32):14309-14.
[3]Beyer C, Reichert H, Akan H, Mallano T, Schramm A, Dees C, Palumbo-Zerr K, Lin NY, Distler A, Gelse K, Varga J, Distler O, Schett G, Distler JH. Blockade of canonical Wnt signalling ameliorates experimental dermal fibrosis. Ann Rheum Dis. 2013 Jul;72(7):1255-8.