686770-61-6

Basic information

• Product Name: IWP-2
• Synonyms: IWP 2;N-(6-Methyl-2-benzothiazolyl)-2-[(3,4,6,7-tetrahydro-4-oxo-3-phenylthieno[3,2-d]pyrimidin-2-yl)thio]-acetamide;Acetamide, N-(6-methyl-2-benzothiazolyl)-2-[(3,4,6,7-tetrahydro-4-oxo-3-phenylthieno[3,2-d]pyrimidin-2-yl)thio]-;IWP 2 N-(6-Methyl-2-benzothiazolyl)-2-[(3,4,6,7-tetrahydro-4-oxo-3-phenylthieno[3,2d]pyrimidin-2-yl)thio]acetamide;IWP 2, >=98%;Wnt Antagonist II, IWP-2;N-(6-methylbenzo[d]thiazol-2-yl)-2-((4-oxo-3-phenyl-3,4,6,7-tetrahydrothieno[3,2-d]pyrimidin-2-yl)thio)acetamide;WNT INHIBITOR IWP-2
• CAS NO: 686770-61-6
• Molecular Formula: C22H18N4O2S3
• Molecular Weight: 467
• Product Categories: Aromatics;Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals;Sulfur & Selenium Compounds;Inhibitors
• Mol File: 686770-61-6.mol
• Article Data: 0

Chemical Properties

• Melting Point: 257 °C(dec.)
• Appearance: /
• Density: 1.52±0.1 g/cm3(Predicted)
• Storage Temp.: Store at +4°C
• Solubility: DMSO: >5mg/mL
• PKA: 9.01±0.70(Predicted)
• Stability: Stable for 2 years from date of purchase as supplied. Solutions in DMSO may be stored at -20° for up to 2 months.
• CAS DataBase Reference: IWP-2(CAS DataBase Reference)
• NIST Chemistry Reference: IWP-2(686770-61-6)
• EPA Substance Registry System: IWP-2(686770-61-6)

Safety Data

• WGK Germany: 2
• Hazardous Substances Data: 686770-61-6(Hazardous Substances Data)

Usage

Description

IWP-2, also known as a cell-permeable benzothiazolyl-acetamide compound, is an inhibitor of Wnt processing and secretion. It selectively blocks the membrane-bound O-acyltransferase (MBOAT) family member Porcn, which is responsible for Wnt palmitoylation. IWP-2 does not affect the Wnt/β-catenin signaling pathway in general and does not display any effect against Wnt-stimulated cellular responses. It is an important tool for probing the involvement of the Wnt pathway in various physiological processes.

Uses

Used in Pharmaceutical Industry:
IWP-2 is used as an inactivator of Porcn function and an inhibitor of Wnt production for the treatment of diseases and conditions such as cancer, degenerative diseases, type II diabetes, and osteopetrosis.
Used in Cancer Research:
IWP-2 is used as a Wnt signaling inhibitor to treat cell lines L-Wnt-3a and L-Wnt-5a, demonstrating its inhibitory effect on Wnt signaling. It is also used to treat WT and Gja1Jrt/+ stromal cells to confirm that the Wnt/β-catenin signaling pathway is not involved in the increased marker expression by Gja1Jrt/+ osteoblasts.
Used in Cell Differentiation:
IWP-2 is used to induce cardiomyocyte differentiation from human pluripotent stem cells, making it a valuable tool for studying the role of Wnt signaling in cell differentiation processes.
Used in Research and Development:
IWP-2 is used as an important tool to probe the involvement of the Wnt pathway in physiological processes, contributing to the understanding of Wnt signaling and its role in various biological functions.

Features

Selective inhibitor of Porcn-mediated Wnt secretion.

In vitro

IWP-2 is useful in both regenerative medicine and anticancer efforts. IWP-2 inactivates Porcn, a membrane-bound O-acyltransferase (MBOAT), and selectively inhibits palmitoylation of Wnt. IWP-2 blocks Wnt-dependent phosphorylation of Lrp6 receptor and Dvl2, and β-catenin accumulation.

Biochem/physiol Actions

IWP-2 is an inactivator of Porcn function; inhibitor of Wnt production. Wnt/b-catenin (‘canonical′) pathway maintains transcriptional programs that enable stem cells to remain multipotent. Hyperactivation of the Wnt/b-catenin pathway leads to disease stage. IWP-2 inhibits Wnt production. It appears that IWP inactivates Porcn function either by directly inhibiting the Porcn active site or by modulating the function of a Porcn regulator. Porcn is a member of the membrane-bound O-acyltransferase (MBOAT) family, which adds a palmitoyl group to Wnt proteins that is essential to their signaling ability and is required for Wnt secretion. IWP-2 is useful in both regenerative medicine and anticancer efforts.

in vitro

expression of porcn but not evi alleviated the effects of iwp-2 on pathway activity and wnt secretion, which suggests that in general iwp-2 may act on porcn [1].

in vivo

in order to test the in vivo activity of iwp-2, the authors turned to a simple and rapid assay of wnt/b-catenin pathway activity: regeneration of the zebrafish caudal fin following resection. the addition of iwp-2 to the aquarium water of zebrafish failed to suppress fin regeneration after mechanical resection, which suggests either that iwp-2 have poor bioavailability or that the determinants in the gene product that they target are not conserved in zebrafish [1].

IC 50

27 nm for wnt pathway activity

References

1) Chen et al. (2009), Small molecule-mediated disruption of Wnt-dependent signaling in tissue regeneration and cancer; Nature Chem. Biol., 5 100 2) Lian et al. (2012), Robust Cardiomyocyte differentiation from human pluripotent stem cells via temporal modulation of canonical Wnt signaling; Proc. Natl. Acad. Sci. USA, 109 1848 3) ten Berge et al. (2011), Embryonic stem cells require Wnt proteins to prevent differentiation to epiblast stem cells; Nature Cell. Biol., 13 1070 4) Uyama et al. (2013), Wasf2: a novel target of intermittent parathyroid hormone administration; Int. J. Mol. Med., 31 1243