ICG-001, Wnt signaling modulator

ICG-001 is a potent and selective Wnt signaling modulator. ICG-001 modulates Wnt signaling and increased the expression of genes beneficial for cardiac regeneration in epicardial cells. ICG-001 binds cAMP-responsive element binding (CREB)-binding protein (CBP) to disrupt its interaction with β-catenin and inhibit CBP function as a coactivator of Wnt/β-catenin-mediated transcription. ICG-001 induces cytotoxicity of multiple myeloma cells in Wnt-independent manner. Note: Chemical structures of ICG-001 and PRI-724 look very close, but they are not the same molecule. Many vendors confused them.

Product information

CAS Number: 780757-88-2

Molecular Weight: 548.63

Formula: C33H32N4O4

Synonym:

ICG 001

ICG001

Related CAS Number:

1422253-38-0 (PRI-724)

847591-62-2 (Deleted CAS#)

721457-27-8 (Deleted CAS#)

1402835-92-0 (Deleted CAS#)

Chemical Name: (6S, 9aS)-6-(4-Hydroxybenzyl)-8-[(naphthalen-1-yl)methyl]-4, 7-dioxohexahydropyrazino[1, 2-a]pyrimidine-1-carboxylic acid N-benzylamide

Smiles: OC1=CC=C(C[C@H]2C(=O)N(C[C@H]3N2C(=O)CCN3C(=O)NCC2C=CC=CC=2)CC2=CC=CC3=CC=CC=C23)C=C1

InChiKey: HQWTUOLCGKIECB-XZWHSSHBSA-N

InChi: InChI=1S/C33H32N4O4/c38-27-15-13-23(14-16-27)19-29-32(40)35(21-26-11-6-10-25-9-4-5-12-28(25)26)22-30-36(18-17-31(39)37(29)30)33(41)34-20-24-7-2-1-3-8-24/h1-16,29-30,38H,17-22H2,(H,34,41)/t29-,30+/m0/s1

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: Solubility (25°C) DMSO: 100 mg/mL(182.27 mM). Water: Insoluble.

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

ICG-001 has no effect on the related reporter construct, FOPFLASH, which contains mutated TCF sites. After treatment with 25μM of ICG-001 for 8 hours, SW480 cell reduces the steady-state levels of Survivin and Cyclin D1 RNA and protein, both of which can be up-regulated by β-catenin. ICG-001 selectively induces apoptosis in transformed cells but not in normal colon cells, reduces in vitro growth of colon carcinoma cells. ICG-001, can phenotypically rescue normal nerve growth factor (NGF) -induced neuronal differentiation and neurite outgrowth in the presenilin-1 mutant cells, emphasizing the importance of the TCF/β-catenin signaling pathway on neurite outgrowth and neuronal differentiation. A recent study demonstrates that 5μM ICG-001 inhibits leptin-induced EMT, invasion and tumorsphere formation in MCF7 cells.

In Vivo:

Administration of a water-soluble analog of ICG-001 for 9 weeks reduces the formation of colon and small intestinal polyps by 42% as effectively as the nonsteroidal antiinflammatory agent Sulindac, which has consistently demonstrated efficacy in this model. No overt toxicity is detected throughout the course of treatment. In the SW620 nude mouse xenograft model of tumor regression, 150 mg/kg, i.v. of analog demonstrates a dramatic reduction in tumor volume over the 19-day course of treatment, with no mortality or weight loss. ICG-001 (5 mg/kg per day) significantly inhibits beta-catenin signaling and attenuates bleomycin-induced lung fibrosis in mice, while concurrently preserving the epithelium.

References:

1. Yan D, et al, J Biol Chem, 2012, 287(11), 8598-8612.
2. Teo JL, et al, Proc Natl Acad Sci USA, 2005, 102(34), 12171-12176.
3. Emami KH, et al, Proc Natl Acad Sci USA, 2004, 101(34), 12682-12687.

Products are for research use only. Not for human use.