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IWP 2 is a potent inhibitor of Wnt processing and secretion (IC50 = 27nM). IWP 2 inactivates PORCN, a membrane-bound O-acyltransferase (MBOAT), and selectively inhibits palmitoylation of Wnt. Blocks Wnt-dependent phosphorylation of Lrp6 receptor and Dvl2, and β-catenin accumulation. IWP 2 suppresses self-renewal in R1 embryonic stem cells and promotes cardiomyocyte differentiation from hPSCs. The compound has also been used in protocols to reprogram human somatic cells to chemically-induced PSCs.
|Storage||Store at +4°C|
The technical data provided above is for guidance only. For batch specific data refer to the Certificate of Analysis.
Tocris products are intended for laboratory research use only, unless stated otherwise.
|Solvent||Max Conc. mg/mL||Max Conc. mM|
|DMSO||2.33||5 with gentle warming|
The following data is based on the product molecular weight 466.6. Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
|Concentration / Solvent Volume / Mass||1 mg||5 mg||10 mg|
|0.05 mM||42.86 mL||214.32 mL||428.63 mL|
|0.25 mM||8.57 mL||42.86 mL||85.73 mL|
|0.5 mM||4.29 mL||21.43 mL||42.86 mL|
|2.5 mM||0.86 mL||4.29 mL||8.57 mL|
References are publications that support the biological activity of the product.
Chen et al (2009) Small molecule-mediated disruption of wnt-dependent signaling in tissue regeneration and cancer. Nature Chem.Biol. 5 100 PMID: 19125156
ten Berge et al (2011) Embryonic stem cells require Wnt proteins to prevent differentiation to epiblast stem cells. Nat.Cell.Biol. 13 1070 PMID: 21841791
Lian et al (2012) Robust cardiomyocyte differentiation from human pluripotent stem cells via temporal modulation of canonical Wnt signaling. Proc.Natl.Acad.Sci.U S A 109 E1848 PMID: 22645348
Noor et al (2019) 3D printing of personalized thick and perfusable cardiac patches and hearts. Adv Sci (Weinh) 6 1900344 PMID: 31179230
Hoang et al (2018) Generation of spatial-patterned early-developing cardiac organoids using human pluripotent stem cells. Nat.Protoc. 13 723 PMID: 29543795
Guan et al (2022) Chemical reprogramming of human somatic cells to pluripotent stem cells. Nature 605 325 PMID: 35418683
If you know of a relevant reference for IWP 2, please let us know.
Keywords: IWP 2, IWP 2 supplier, MBOAT, membrane-bound, o-acyltransferases, Porcupine, porcn, wnt, secretion, production, signaling, signalling, inhibitors, inhibits, inactivators, inactivates, IWP2, beta-catenin, β-catenin, b-catenin, stem, cells, proliferation, reprogramming, ciPSC, pluirpotent, Stem, Cell, Signaling, Proliferation, PORCN, Organoids, Cardiomyocyte, Cells, Reprogramming, 3533, Tocris Bioscience
Citations are publications that use Tocris products. Selected citations for IWP 2 include:
Yang et al (2020) A Human Pluripotent Stem Cell-based Platform to Study SARS-CoV-2 Tropism and Model Virus Infection in Human Cells and Organoids Cell Stem Cell 27 125 PMID: 32579880
Rostovskaya et al (2019) Capacitation of human naïve pluripotent stem cells for multi-lineage differentiation. Development 146 PMID: 30944104
Schneider et al (2019) User-Friendly and Parallelized Generation of Human Induced Pluripotent Stem Cell-Derived Microtissues in a Centrifugal Heart-on-a-Chip. Tissue Eng Part A 25 786 PMID: 30968738
Wang et al (2019) Point mutations in the PDX1 transactivation domain impair human β-cell development and function. Mol Metab 24 80 PMID: 30930126
Shekhar et al (2018) ETV1 activates a rapid conduction transcriptional program in rodent and human cardiomyocytes. Sci Rep 8 9944 PMID: 29967479
Lin et al (2018) Efficient differentiation of cardiomyocytes and generation of calcium-sensor reporter lines from nonhuman primate iPSCs. Sci Rep 8 5907 PMID: 29651156
Capowski et al (2016) Regulation of WNT Signaling by VSX2 During Optic Vesicle Patterning in Human Induced Pluripotent Stem Cells. Stem Cells 34 2625 PMID: 27301076
Huang et al (2015) The in vitro generation of lung and airway progenitor cells from human pluripotent stem cells. Sci Rep 10 413 PMID: 25654758
Lee et al (2015) A systems-biological study on the identification of safe and effective molecular targets for the reduction of ultraviolet B-induced skin pigmentation. Nat Commun 5 10305 PMID: 25980672
Freedman et al (2015) Modelling kidney disease with CRISPR-mutant kidney organoids derived from human pluripotent epiblast spheroids. Nat Cell Biol 6 8715 PMID: 26493500
Ditadi et al (2015) Human definitive haemogenic endothelium and arterial vascular endothelium represent distinct lineages. Stem Cell Res 17 580 PMID: 25915127
Kempf et al (2014) Controlling expansion and cardiomyogenic differentiation of human pluripotent stem cells in scalable suspension culture. Stem Cell Reports 3 1132 PMID: 25454631
Huang et al (2014) Efficient generation of lung and airway epithelial cells from human pluripotent stem cells. Nat Biotechnol 32 84 PMID: 24291815
Lee and Evans (2019) TMEM88 Inhibits Wnt Signaling by Promoting Wnt Signalosome Localization to Multivesicular Bodies. iScience 19 267 PMID: 31401350
Nakanishi et al (2019) Geometrical Patterning and Constituent Cell Heterogeneity Facilitate Electrical Conduction Disturbances in a Human Induced Pluripotent Stem Cell-Based Platform: An In vitro Disease Model of Atrial Arrhythmias. Front Physiol 10 818 PMID: 31316396
Perales-Clemente et al (2016) Natural underlying mtDNA heteroplasmy as a potential source of intra-person hiPSC variability. EMBO J 35 1979 PMID: 27436875
Datta et al (2016) Label-free imaging of metabolism and oxidative stress in human induced pluripotent stem cell-derived cardiomyocytes. Biomed Opt Express 7 1690 PMID: 27231614
Lin et al (2016) HP Promotes Cardiac Differentiation of Human Pluripotent Stem Cells in Chemically Defined Albumin-Free Medium, Enabling Consistent Manufacture of Cardiomyocytes. Stem Cells Transl Med PMID: 27591141
Xu et al (2016) Wnt/β-catenin signaling promotes self-renewal and inhibits the primed state transition in naïve human embryonic stem cells. Proc Natl Acad Sci U S A 113 E6382 PMID: 27698112
Faisy et al (2014) Wnt/β-catenin signaling modulates human airway sensitization induced by β2-adrenoceptor stimulation. PLoS One 9 e111350 PMID: 25360795
Vahdat et al (2019) Establishment of A Protocol for In Vitro Culture of Cardiogenic Mesodermal Cells Derived from Human Embryonic Stem Cells. Cell J 20 496 PMID: 30123995
Xiang et al (2019) Long-term functional maintenance of primary human hepatocytes in vitro. Science 364 399 PMID: 31023926
Yap et al (2019) In Vivo Generation of Post-infarct Human Cardiac Muscle by Laminin-Promoted Cardiovascular Progenitors. Cell Rep 26 3231 PMID: 30893597
Kennedy et al (2016) Sp5 and Sp8 recruit β-catenin and Tcf1-Lef1 to select enhancers to activate Wnt target gene transcription. Proc Natl Acad Sci U S A 113 3545 PMID: 26969725
Hojo et al (2013) Hedgehog-Gli activators direct osteo-chondrogenic function of bone morphogenetic protein toward osteogenesis in the perichondrium. J Biol Chem 288 9924 PMID: 23423383
Walko et al (2017) A genome-wide screen identifies YAP/WBP2 interplay conferring growth advantage on human epidermal stem cells. Nat Commun 8 14744 PMID: 28332498
Lee et al (2017) Human Pluripotent Stem Cell-Derived Atrial and Ventricular Cardiomyocytes Develop from Distinct Mesoderm Populations. Cell Stem Cell 21 179 PMID: 28777944
Tong (2017) Degree of tissue differentiation dictates susceptibility to BRAF-driven colorectal cancer. Cell Rep 21 3833 PMID: 29281831
Magro-Lopez et al (2018) Effects of lung and airway epithelial maturation cocktail on the structure of lung bud organoids. Stem Cell Res.Ther. 9 186 PMID: 29996941
Kling et al (2018) Temporal Regulation of Natural Killer T Cell Interferon Gamma Responses by β-Catenin-Dependent and -Independent Wnt Signaling. Front Immunol 9 483 PMID: 29616022
Shi et al (2017) Genome Editing in hPSCs Reveals GATA6 Haploinsufficiency and a Genetic Interaction with GATA4 in Human Pancreatic Development. Cell Stem Cell 20 675 PMID: 28196600
Lin et al (2017) Culture in Glucose-Depleted Medium Supplemented with Fatty Acid and 3,3',5-Triiodo-l-Thyronine Facilitates Purification and Maturation of Human Pluripotent Stem Cell-Derived Cardiomyocytes. Front Endocrinol (Lausanne) 8 253 PMID: 29067001
Kumar et al (2015) Generation of an expandable intermediate mesoderm restricted progenitor cell line from human pluripotent stem cells. Elife 4 PMID: 26554899
Kim et al (2015) Act.-A and Bmp4 levels modulate cell type specification during CHIR-induced cardiomyogenesis. PLoS One 10 e0118670 PMID: 25706534
Heylman et al (2015) Supervised Machine Learning for Classification of the Electrophysiological Effects of Chronotropic Drugs on Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes. PLoS One 10 e0144572 PMID: 26695765
Huebsch et al (2015) Automated Video-Based Analysis of Contractility and Calcium Flux in Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes Cultured over Different Spatial Scales. Tissue Eng Part C Methods 21 467 PMID: 25333967
Lee et al (2015) Machine learning plus optical flow: a simple and sensitive method to detect cardioactive drugs. Sci Rep 5 11817 PMID: 26139150
Skelton et al (2014) SIRPA, VCAM1 and CD34 identify discrete lineages during early human cardiovascular development. Nat Genet 13 172 PMID: 24968096
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IWP2 was used for cardiomyocyte differentiation of pluripotent stem cells. IWP2 was used at a concentration of 5 uM on day 3 of the differentiation schedule. The image shows differentiated cardiomyocytes.
I use it as a blocking molecule of the WNT pathway for cardiac differentiation in foreskin fibroblast-derive IPS cells. I obtained succesfully cardiomyocytes in a 5uM concentration.
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