|
| 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%;IWP-2;IWP 2;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 | | CAS: | 686770-61-6 | | MF: | C22H18N4O2S3 | | MW: | 466.6 | | EINECS: | | | Product Categories: | Inhibitors;Aromatics;Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals;Sulfur & Selenium Compounds | | Mol File: | 686770-61-6.mol |  |
| | IWP-2 Chemical Properties |
| Melting point | 257 °C(dec.) | | density | 1.52±0.1 g/cm3(Predicted) | | storage temp. | room temp | | solubility | DMSO: >5mg/mL | | pka | 9.01±0.70(Predicted) | | form | powder | | color | Beige | | Stability: | Stable for 2 years from date of purchase as supplied. Solutions in DMSO may be stored at -20° for up to 2 months. | | InChIKey | WRKPZSMRWPJJDH-UHFFFAOYSA-N | | CAS DataBase Reference | 686770-61-6 |
| WGK Germany | 2 | | HS Code | 2934.20.8000 |
| | IWP-2 Usage And Synthesis |
| Description | IWP-2 is an inhibitor of Wnt processing and secretion with IC50 of 27 nM in a cell-free assay, selective blockage of Porcn-mediated Wnt palmitoylation, does not affect Wnt/β-catenin in general and displays no effect against Wnt-stimulated cellular responses. | | 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. | | Description | IWP-2 (686770-61-6) is an inhibitor of Wnt secretion and processing. It blocks Wnt-dependent signaling (IC50= 27 nM) by inhibition of the O-acyltransferase Porcn.1 Induces cardiomyocyte differentiation from human pluripotent stem cells.2 IWP-2 is an important tool to probe the involvement of the Wnt pathway in physiological processes.3,4?Cell permeable. | | Uses | IWP-2 is an inactivator of Porcn function; inhibitor of Wnt production. IWP-2 is useful in the treatment diseases and conditions such as cancer, degenerative diseases, type II diabetes and osteopetrosis. | | Uses | IWP-2 has been used to treat the cell lines L-Wnt-3a and L-Wnt-5a, to demonstrate the inhibitory effect of IWP-2. It has also been used as a Wnt signaling inhibitor to treat WT and?Gja1Jrt/+ stromal cells to confirm that, theWnt/β-catenin signaling pathway pathway was not involved in the increased marker expression by?Gja1Jrt/+ osteoblasts. | | Definition | ChEBI: N-(6-methyl-1,3-benzothiazol-2-yl)-2-[(4-oxo-3-phenyl-6,7-dihydrothieno[3,2-d]pyrimidin-2-yl)thio]acetamide is an organonitrogen heterocyclic compound, an organic heterobicyclic compound and an organosulfur heterocyclic compound. | | General Description | A cell-permeable benzothiazolyl-acetamide compound that inhibits the cellular Wnt processing and secretion via selective blockage of MBOAT (membrane-bound O-acyltranferase) family member Porcn- (Porcupine) mediated Wnt palmitoylation. IWP-2 does not affect Wnt/β-catenin signaling pathway in general and, unlike IWR-1-endo (Cat. No. 681669), displays no effect against Wnt-stimulated cellular responses. Also available as a 10 mM solution in DMSO (Cat. No. 506072). | | 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 | | storage | +4°C | | 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 |
| | IWP-2 Preparation Products And Raw materials |
|
