Stemolecule™ Wnt Inhibitor IWP-4

Wnt Inhibitor IWP-4 was identified in a high throughput screen for antagonists of the Wnt / β-catenin pathway. Wnt Inhibitor IWP-4 prevents palmitylation of Wnt proteins by Porcupine (Porcn), a membrane-bound O-acyltransferase, there by blocking Wnt secretion and activity. It also blocks phosphorylation of the Lrp6 receptor and accumulation of both Dvl2 and β-catenin¹.

New 50 mg size now available.

Stemgent and the Stemolecule brand name are trademarks of REPROCELL Inc., Japan.

Product Name: Stemolecule Wnt Inhibitor IWP-4

Catalog Number: 04-0036

Size: 2 mg

Alternate Name(s): 2-(3,4,6,7-tetrahydro-3-(2-methoxyphenyl)-4-oxothieno[3,2-d]pyrimidin-2-ylthio)-N-(6-methylbenzo[d]thiazol-2-yl)acetamide

Chemical Formula: C₂₃H₂₀N₄O₃S₃

Molecular Weight: 496.62

CAS Number: 686772-17-8

Purity: Greater than 96 % by HPLC analysis

Formulation: White solid

Solubility: This molecule is reported to be soluble in DMSO at 1.2 mM.

Reconstitution: For a 1.2 mM concentrated stock solution of Wnt Inhibitor IWP-4, reconstitute the compound by adding 3.36 mL of DMSO to the entire contents of the vial. If precipitate is observed, warm the solution to 37 °C for 2 to 5 minutes. For use in cell culture, keep the total DMSO concentration less than 0.1%.

Storage and Stability: Store powder at 4 °C protected from light. Information about the stability of Stemolecules in solution is largely not available. As a general guideline, we recommend that stock solution be freshly made and stored in aliquots at − 20 °C, protected from light. The effect of storage of stock solutions should be verified for each application.

Quality Control: The purity of Wnt Inhibitor IWP-4 was determined by HPLC analysis. The accurate mass was determined by mass spectrometry. Cellular toxicity of Wnt Inhibitor IWP-4 was tested on mouse embryonic stem cells.

Specification Sheets:

• 04-0036 Specifications Sheet

Safety Data Sheets:

• 04-0036 Safety Data Sheet

1. Chen, B., Dodge, M.E., Tang, W., Lu, J., Ma, Z., Fan, C.W., Wei, S., Hao, W., Kilgore, J., Williams, N.S., Roth, M.G., Amatruda, J.F., Chen, C., and Lum, L. Small molecule-mediated disruption of Wnt-dependent signaling in tissue regeneration and cancer. Nat Chem Biol 5: 100-107 (2009).

Additional Publications

• Xu Y; Qi J; Zhou W; Liu X; Zhang L; Yao X; Wu H. Generation of ring-shaped human iPSC-derived functional heart microtissues in a Möbius strip configuration. Bio-Design and Manufacturing 5:687 (2022).
• Jimenez-Vazquez EN; Jain A; Jones DK. Enhancing iPSC-CM Maturation Using a Matrigel-Coated Micropatterned PDMS Substrate. Current Protocols 2:e601 (2022).
• Jiang L; Liang J; Juang W; Ma J; Park KH; Wu Z; Chen P; Zhu H; Ma J-J; Cai W; Paul C; Niu L; Fan G-C; Wang H-S; Kanisicak O; Xu M; Wang Y. CRISPR activation of endogenous genes reprograms fibroblasts into cardiovascular progenitor cells for myocardial infarction therapy. Molecular Therap 30:54 (2022).
• Cui M; Atmanli A; Morales MG; Tan W; Chen K; Xiao X; Xu L; Liu N; Bassel-Duby R; Olson EN;. Nrf1 promotes heart regeneration and repair by regulating proteostasis and redox balance. Nature Commun 12:5270 (2021).
• Osada H; Kawatou M; Fujita D; Yabata Y; Minatoya K; Yamashita JK; Masumoto H. Therapeutic potential of clinical-grade human induced pluripotent stem cell-derived cardiac tissues. JTCVS Open 8:359-374 (2021).
• Cui M; Atmanli A; Morales MG; Tan W; Chen K; Xiao X; Xu L; Liu N; Bassel-Duby R; Olson EN;. Nrf1 promotes heart regeneration and repair by regulating proteostasis and redox balance. Nature Commun 12:5270 (2021).
• Dasi A; Hernández-Romero I; Gomez JF; Climent AM; Ferrero JM; Trenor B. Analysis of the response of human iPSC-derived cardiomyocyte tissue to I_CaL block. A combined in vitro and in silico approach. Computers Biology Med 137:104796 (2021).
• Schoger E; Zimmermanm W-H; Cyganek L Zalarayán LC. Establishment of a second generation homozygous CRISPRa human induced pluripotent stem cell (hiPSC) line for enhanced levels of endogenous gene activation. Stem Cell Res 56:102518 (2021).
• Tan JJ; Guyette JP; Miki K; Xiao L Kaur G; Wu T; Zhu L; Hansen KJ; Ling K-H; Milan DJ; Ott HC. Human iPS-derived pre-epicardial cells direct cardiomyocyte aggregation expansion and organization in vitro. Nature Commun 12:4997 (2021).
• Branca MA; Dias TP Cotovio JP; Rodrigues CAV; Fernandes TG; Cabra; JMS; Diogo MM. 3D Microwell Platform for Cardiomyocyte Differentiation of Human Pluripotent Stem Cells. Methods Mol Biol doi.org/10.1007/7651_2020_336: (2020).
• Miwa T; Idiris J; Kumagai H. A novel cardiac differentiation method of a large number and uniformly-sized spheroids using microfabricated culture vessels. Regen Therap 15:18-26 (2020).
• Bejoy J; Bijonowski BM; Marzano M; Jeske R; Ma T; Li Y. Wnt-Notch Signaling Interactions during Neural and Astroglial Patterning of Human Stem Cells. Tissue Engineering Part A In press:doi.org/10.1089/ten.TEA.2019.0202 (2019).
• Kyndiah A; Leonardi F; Tarantino C; Cramer T; Millan-Solsona R; Garetta E; Montserrat N; Mas-Torrent M; Gomila G. Bioelectronic recordings of cardiomyocytes with accumulation mode Electrolyte Gated Organic Field Effect Transistors. Biosensors Bioelectronics in press:111844 (2019).
• Saraiva JE. Population-Level Dynamics of Human Pluripotent Stem Cell Fate Transitions. Universidade de Lisboa Ph.D. Thesis: (2019).
• Atmanli A; Hu D; Deiman FE; van de Vrugt AM; Black III LD; Domian IJ. Multiplex Live Single-Cell Transcriptional Analysis Demarcates Cellular Functional Heterogeneity. eLIFE 8:e49599 (2019).
• Hoirkoshi Y; Yan Y; Terashvili M; Wells C; Horikosih H; Fujita S; Bosnjak ZJ; Bai X. Fatty Acid-Treated Induced Pluripotent Stem Cell-Derived Human Cardiomyocytes Exhibit Adult Cardiomyocyte-Like Energy Metabolism Phenotypes. Cells 8:1095 (2019).
• Marzano M Bejoy J;' Cheerathodi MR; Sun L; York SB; Zhao J; Kanakiyo T; Bu G; Meckes Jr. DG; Li Y. Differential Effects of Extracellular Vesicles of Lineage-Specific Human Pluripotent Stem Cells on the Cellular Behaviors of Isogenic Cortical Spheroids. Cells 8:993 (2019).
• Kuroda T; Yasuda S; Tachi S; Matsuyama S; Kusakawa S; Tano K; Miura T; Matsuyama A; Soto Y. SALL3 expression balance underlies lineage biases in human induced pluripotent stem cell differentiation. Nature Commun 10:2175 (2019).
• Sattler K; El-Battrawy I; Zhao Z; Schrottenberg C; Yücel G; Lan H; Li X; Lang S; Zimmermann W-H; Cyganek L Utikal J; Wieland T; Ravens R; Bieback K; Borggrefe M; Zhou X; Akin I. Serum of patients with acute myocardial infarction prevents inflammation in iPSC-cardiomyocytes. Sci Rep 9:5651 (2019).
• Schlick SF. Fibroblast-Cardiomyocyte Cross-Talk in Heart Muscle Formation and Function. Ph.D. Thesis, Georg-August University Göttingen : (2018).
• Yan Y W; Bejoy J; Xia J; Griffin K; FUan J; Li Y. Cell population balance of cardiovascular spheroids derived from human induced pluripotent stem cells. Sci Rep 9:1295 (2019).
• Bejoy J; Wng Z; Bihonowski B; Yang M; Ma T; Sang Q-XA; Li Y. Differential effects of heparin and hyaluronic acid on neural patterning of human induced pluripotent stem cells. ACS Biomater Sci Eng in press:DOI: 10.1021/acsbiomaterials.8b01142 (2018).
• Chai S; Wan X; Ramierez-Navarro A; Tesar PJ; Kaufman ES; Ficker E; George Al; Deschenes I. Physiological genomics identifies genetic modifiers of long QT syndrome type 2 severity. Journal Clinical Investigation doi:10.1172/JCI94996: (2018).
• Long C; Li H; Tiburcy M; Rodriguez-Cayedo C; Kyrychenko V; Zhou H; Zhang Y; Min Y-L; Shelton JM; Mammen PPA; Liaw NY; Zimmermann W-H; Bassel-Duby R; Schneider JW; Olson EN. Correction of diverse muscular dystrophy mutations in human engineered heart muscle by single-site genome editing. Science Advances 4:eaap9004 (2018).
• Yang J; Karu K; Edwards JG; Eisenberg CA; Eisenberg LM. Inhibition of Histone Methyltransferase, Histone Deacetylase, and β-Catenin Synergistically Enhance the Cardiac Potential of Bone Marrow Cells. Stem Cells International 2017:3464953 (2017).
• Noack C; Haupt LP; Zimmerman W-H; Streckfuss-Bomeke; Zelarayan LC. Generation of a KLF15 homozygous knockout human embryonic stem cell line using paired CRISPR/Cas9n, and human cardiomyocytes derivation. Stem Cell Research23:127-131 (2017).
• Titmarsh DM; Glass NR; Mills RJ; Hidalgo A; Volvetang EJ; Porrello ER; Hudson JE; Cooper-White JJ. "Induction of human iPSC-derived cardiomyocyte proliferation revealed by combinatorial screening in high density microbioreactor arrays." Sci Rep 6:24637 (2016).
• Yang J; Kaur K; Ong LL; Eisenberg CA; Eisenberg LM. "Inhibition of G9a histone methyltransferase converts bbone marrow mesenchymal stem cells to cardiac competent progenitors." Stem Cells International Article 270428 (2015). doi:10.1155/2015/270428
• Cho SW; Park J-S; Heo HJ; Park S-W; Song S; Kim I; Han Y-M; Yanashita JK; Youm JB; Han J; Koh GY. "Dual modification of the mitochondrial permeability transition pore and redox signaling synergistically promotes cardiomyocyte differentiation from pluripotent stem cells." J Am Heart Assoc2014;3:e000693 (2014).
• Lian, X., Hsiao, C., Wilson, G, Zhu, K., Hazeltine, L.B., Azarin, S.M., Raval, K.K., Zhang, J., Kamp, T.J., and Palecek, S.P. Robust cardiomyocyte differentiation from human pluripotent stem cells via temporal modulation of canonical Wnt signaling. Proc Natl Acad Sci USA 109: E1848 (2012).
• Hudson, J., Titmarsh, D., Hidalgo, A., Wolvetang, E., and Cooper-White, J. (2011) Primitive Cardiac Cells from Human Embryonic Stem Cells. Stem Cells Dev 21:1513 (2012).