| Identification | Back Directory | [Name]
IWP-2 | [CAS]
686770-61-6 | [Synonyms]
IWP 2
IWP 2, >=98%
Wnt Antagonist II, 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 | [Molecular Formula]
C22H18N4O2S3 | [MDL Number]
MFCD04457599 | [MOL File]
686770-61-6.mol | [Molecular Weight]
467 |
| Chemical Properties | Back Directory | [Melting point ]
257 °C(dec.) | [density ]
1.52±0.1 g/cm3(Predicted) | [storage temp. ]
Store at +4°C | [solubility ]
DMSO: >5mg/mL | [form ]
powder | [pka]
9.01±0.70(Predicted) | [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. | [InChI]
InChI=1S/C22H18N4O2S3/c1-13-7-8-15-17(11-13)31-21(23-15)25-18(27)12-30-22-24-16-9-10-29-19(16)20(28)26(22)14-5-3-2-4-6-14/h2-8,11H,9-10,12H2,1H3,(H,23,25,27) | [InChIKey]
WRKPZSMRWPJJDH-UHFFFAOYSA-N | [SMILES]
C(NC1=NC2=CC=C(C)C=C2S1)(=O)CSC1N(C2=CC=CC=C2)C(=O)C2SCCC=2N=1 | [CAS DataBase Reference]
686770-61-6 |
| Hazard Information | Back Directory | [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. | [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 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]
Store at -20°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 |
| Questions And Answer | Back Directory | [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. |
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