ICG 001
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.
- 1. Yan Wang, Ziwei Kuang, et al. "Proximal tubular FHL2, a novel downstream target of hypoxia inducible factor 1, is a protector against ischemic acute kidney injury." Cell Mol Life Sci. 2024 May 30;81(1):244. PMID: 38814462
- 2. Mengru Gu, Hanlu Jiang, et al. "Palmitoyltransferase DHHC9 and acyl protein thioesterase APT1 modulate renal fibrosis through regulating β-catenin palmitoylation." Nat Commun. 2023 Oct 21;14(1):6682. PMID: 37865665
- 3. Mingxin Wen, Hui Ren, et al. "CT45A1 promotes the metastasis of osteosarcoma cells in vitro and in vivo through β-catenin." Cell Death Dis. 2021 Jun 25;12(7):650. PMID: 34172717
- 4. Duan Y, Qiu Y, et al. "Deletion of FHL2 in fibroblasts attenuates fibroblasts activation and kidney fibrosis via restraining TGF-β1-induced Wnt/β-catenin signaling." J Mol Med (Berl). 2020; 98 (2): 291–307. PMID: 31927599
- 5. Fatima I, El-Ayachi I, et al. "Simultaneous Multi-Organ Metastases from Chemo-Resistant Triple-Negative Breast Cancer Are Prevented by Interfering with WNT-Signaling." Cancers (Basel). 2019 Dec 17; 11 (12). pii: E2039. PMID: 31861131
- 6. Wasnik S, Lakhan R, et al. "Cyclooxygenase 2 augments osteoblastic but suppresses chondrocytic differentiation of CD90(+) skeletal stem cells in fracture sites." Sci Adv. 2019 Jul 31; 5 (7): eaaw2108. PMID: 31392271
- 7. Zhou J, Toh SH, et al. "A loss-of-function genetic screening reveals synergistic targeting of AKT/mTOR and WTN/β-catenin pathways for treatment of AML with high PRL-3 phosphatase." J Hematol Oncol. 2018 Mar 7; 11 (1): 36. PMID: 29514683
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 548.63 |
| Cas No. | 847591-62-2 |
| Formula | C33H32N4O4 |
| Solubility | ≥27.43 mg/mL in DMSO; insoluble in H2O; ≥35.47 mg/mL in EtOH with ultrasonic |
| Chemical Name | (6S,9aS)-N-benzyl-6-[(4-hydroxyphenyl)methyl]-8-(naphthalen-1-ylmethyl)-4,7-dioxo-3,6,9,9a-tetrahydro-2H-pyrazino[1,2-a]pyrimidine-1-carboxamide |
| SDF | Download SDF |
| Canonical SMILES | C1CN(C2CN(C(=O)C(N2C1=O)CC3=CC=C(C=C3)O)CC4=CC=CC5=CC=CC=C54)C(=O)NCC6=CC=CC=C6 |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment: [1] | |
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Cell lines |
Rat Epicardial Cells |
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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°C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20°C for several months. |
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Reaction Conditions |
10 μM, 24 hours |
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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 experiment: [1] | |
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Animal models |
Female Sprague-Dawley rats |
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Dosage form |
Subcutaneous injection, 50 mg/kg/day |
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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. |
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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. |
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References: [1] Sasaki T, Hwang H, Nguyen C, et al. The small molecule Wnt signaling modulator ICG-001 improves contractile function in chronically infarcted rat myocardium. PloS one, 2013, 8 (9): e75010. |
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| Description | ICG-001 is an antagonist of Wnt/β-catenin/TCF-mediated transcription and specifically binds to element-binding protein (CBP) with IC50 of 3 μM | |||||
| Targets | CBP | |||||
| IC50 | 3 μM | |||||
Quality Control & MSDS
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