IWP-3 Chemical Properties

Melting point:

>248°C (dec.)

storage temp. 

2-8°C

solubility 

DMSO: soluble2mg/mL (clear solution, warmed)

form 

powder

color 

white to beige

InChI

1S/C22H17FN4O2S3/c1-12-2-7-15-17(10-12)32-21(24-15)26-18(28)11-31-22-25-16-8-9-30-19(16)20(29)27(22)14-5-3-13(23)4-6-14/h2-7,10H,8-9,11H2,1H3,(H,24,26,28)

InChIKey

XVMHQSDMKWQNBK-UHFFFAOYSA-N

SMILES

Cc1ccc2nc(NC(=O)CSC3=NC4=C(SCC4)C(=O)N3c5ccc(F)cc5)sc2c1

Safety Information

Hazard Codes 

Xn

Risk Statements 

22

WGK Germany 

3

Storage Class

13 - Non Combustible Solids

Hazard Classifications

Acute Tox. 4 Oral

IWP-3 Usage And Synthesis

Uses

IWP-3 is a potent inhibitor for porcupine which is known to catalyze the palmitoylation of Wnt proteins which are crucial in tumorigenesis.

Biological Activity

iwp-3 is an inhibitor of wnt production.wnt signaling proteins, a group of small secreted proteins, are active in tissue homeostasis, embryonic development, as well as tumorigenesis. wnt proteins can bind to the cell surface receptors, initiating a signaling cascade that results in the β-catenin activation of gene transcription.

Biochem/physiol Actions

IWP-3 is a Wnt inhibitor that prevents palmitylation of Wnt proteins by Porcupine (Porcn). IWP-3 is an inactivator of Porcn function that acts as inhibitors of Wnt production. Studies revealed that IWP-3 induces differentiation of human mesoderm cells to form cardiomyocytes.

in vitro

in previous study, iwp-3 was identified as an inhibitor of wnt production that could regulate in vitro wnt pathway activity with an ic50 value of 40 nm. in addition, iwp-3 was found to be able to inactivate porcupine, a o-acyltransferase for palmitoylating wnt proteins that was critical for the signaling ability and secretion. moreover, iwp-3 at 5 μm was found to block wnt-dependent phosphorylation of the low-density lipoprotein receptor-related protein 6 and the scaffold protein dishevelled, resulting in preventing the accumulation of β-catenin [1]. in another study, iwp-3 was applied to promote cardiomyocyte generation from human embryonic stem cells by inhibiting wnt signaling [2].

IC 50

40 nm

References

[1] b. chen, m. e. dodge, w. tang, et al. small molecule-mediated disruption of wnt-dependent signaling in tissue regeneration and cancer. nature chemical biology 5(2), 100-107 (2009).
[2] e. willems, s. spiering, h. davidovics, et al. small molecule inhibitors of the wnt pathway potently promote cardiomyocytes from human embryonic stem cell derived mesoderm. circulation research 109(4), 360-364 (2011).