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Biological Activity for Wnt-C59
Wnt-C59 is a highly potent inhibitor of MBOAT (membrane-bound O-acyltranferase) family member Porcupine (PORCN) (IC50 = 74 pM) that mediates WNT palmitoylation and secretion. Wnt-C59 potently inhibits the processing of both canonical (1, 2, 3a, 6, 7b, 8a, 9a, 9b, 10) and non-canonical (4, 5a, 11, 16) Wnt subtypes. Wnt-C59 blocks progression of mammary tumors in MMTV-WNT1 transgenic mice and downregulates Wnt/β-catenin target genes. Wnt-C59 treated tumors show a decrease in β-catenin, CyclinD1 and c-Myc. Wnt-C59 induces cardiomyocyte differentiation from human iPSCs following culture with CHIR 99021 (Cat. No. 4423). Wnt-C59 efficiently induces neural differentiation of CTIP2+/COUP-TF1- cells from PSCs in culture. When grafted into the cortex of adult mice, Wnt-C59-treated cells develop abundant axonal fiber extensions toward the spinal cord. The compound has also been used in protocls to generate β cells from human PSCs. Cell permeable and orally bioavailable.
Compound Libraries for Wnt-C59
Technical Data for Wnt-C59
|Storage||Store at -20°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.
Solubility Data for Wnt-C59
|Solvent||Max Conc. mg/mL||Max Conc. mM|
Preparing Stock Solutions for Wnt-C59
The following data is based on the product molecular weight 379.45. 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|
|0.2 mM||13.18 mL||65.88 mL||131.77 mL|
|1 mM||2.64 mL||13.18 mL||26.35 mL|
|2 mM||1.32 mL||6.59 mL||13.18 mL|
|10 mM||0.26 mL||1.32 mL||2.64 mL|
References for Wnt-C59
References are publications that support the biological activity of the product.
Proffitt et al (2013) Pharmacological inhibition of the Wnt acyltransferase PORCN prevents growth of WNT-driven mammary cancer. Cancer Res. 73 502 PMID: 23188502
Wend et al (2013) WNT10B/β-catenin signalling induces HMGA2 and proliferation in metastatic triple-negative breast cancer. EMBO Mol.Med. 5 264 PMID: 23307470
Youssef et al (2012) Adult interfollicular tumour-initiating cells are reprogrammed into an embryonic hair follicle progenitor-like fate during basal cell carcinoma initiation. Nat. Cell Biol. 14 1282 PMID: 23178882
Burridge et al (2014) Chemically defined generation of human cardiomyocytes. Nat.Methods 11 855 PMID: 24930130
Motono et al (2016) WNT-C59, a small-molecule WNT inhibitor, efficiently induces anterior cortex that includes cortical motor neurons from human pluripotent stem cells. Stem Cells Transl.Med. 5 552 PMID: 26941358
Jiang et al (2021) Generation of pancreatic progenitors from human pluripotent stem cells by small molecules. Stem Cell Rep. 16 2395 PMID: 34450037
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Keywords: Wnt-C59, Wnt-C59 supplier, Highly, potent, porcn, inhibitors, inhibits, membrane-bound, O-acyltransferase, MBOAT, Wnt, signaling, pathways, WntC59, PORCN, Cardiomyocyte, Stem, Cells, ESCs, and, iPSC, Organoids, 5148, Tocris Bioscience
49 Citations for Wnt-C59
Citations are publications that use Tocris products. Selected citations for Wnt-C59 include:
Bernatik et al (2017) A Novel Role for the BMP Antagonist Noggin in Sensitizing Cells to Non-canonical Wnt-5a/Ror2/Disheveled Pathway Activation. Front Cell Dev Biol 5 47 PMID: 28523267
Marczenke et al (2017) Cardiac Subtype-Specific Modeling of Kv1.5 Ion Channel Deficiency Using Human Pluripotent Stem Cells. Front Physiol 8 469 PMID: 28729840
Timothy C et al (2022) Contribution of Trp63CreERT2-labeled cells to alveolar regeneration is independent of tuft cells. Elife 11 PMID: 36129169
Guanghao et al (2022) Single-cell sequencing reveals lineage-specific dynamic genetic regulation of gene expression during human cardiomyocyte differentiation. PLoS Genet 18 e1009666 PMID: 35061661
Olivier et al (2022) Paraxial mesoderm organoids model development of human somites. Elife 11 PMID: 35088712
Wenqi et al (2022) Reengineering Ponatinib to Minimize Cardiovascular Toxicity. Cancer Res 82 2777-2791 PMID: 35763671
Nathalie et al (2022) Virus-induced inhibition of cardiac pacemaker channel HCN4 triggers bradycardia in human-induced stem cell system. Cell Mol Life Sci 79 440 PMID: 35864219
Gordana et al (2022) STK25 inhibits PKA signaling by phosphorylating PRKAR1A. Cell Rep 40 111203 PMID: 35977512
Aaron M et al (2022) SOX transcription factors direct TCF-independent WNT/β-catenin responsive transcription to govern cell fate in human pluripotent stem cells. Cell Rep 40 111247 PMID: 36001974
Jose E et al (2022) Time-regulated transcripts with the potential to modulate human pluripotent stem cell-derived cardiomyocyte differentiation. Stem Cell Res Ther 13 437 PMID: 36056380
Anna M et al (2022) Functional microvascularization of human myocardium in vitro. Cell Rep Methods 2 100280 PMID: 36160044
Yulia V et al (2023) Engineered cardiac tissue model of restrictive cardiomyopathy for drug discovery. Cell Rep Med 4 100976 PMID: 36921598
Tim et al (2023) A pesticide and iPSC dopaminergic neuron screen identifies and classifies Parkinson-relevant pesticides. Nat Commun 14 2803 PMID: 37193692
Guiscard et al (2023) Optimized synthesis and pharmacological evaluation of HCN channel inhibitor EC18. Arch Pharm (Weinheim) 356 e2200665 PMID: 36949271
Sergio et al (2023) IGF-1 boosts mitochondrial function by a Ca2+ uptake-dependent mechanism in cultured human and rat cardiomyocytes. Front Physiol 14 1106662 PMID: 36846332
Guiscard et al (2015) Universal cardiac induction of human pluripotent stem cells in two and three-dimensional formats: implications for in vitro maturation. Stem Cells 33 1456-69 PMID: 25639979
Pfeiffer et al (2018) Cardiogenic programming of human pluripotent stem cells by dose-controlled activation of EOMES. Nat Commun 9 440 PMID: 29382828
Shafa et al (2018) Human-Induced Pluripotent Stem Cells Manufactured Using a Current Good Manufacturing Practice-Compliant Process Differentiate Into Clinically Relevant Cells From Three Germ Layers. Front Med (Lausanne) 5 69 PMID: 29600249
Hoes et al (2018) Iron deficiency impairs contractility of human cardiomyocytes through decreased mitochondrial function. Eur J Heart Fail 20 910 PMID: 29484788
Montefiori et al (2018) A promoter interaction map for cardiovascular disease genetics. Elife 7 PMID: 29988018
Pavlovic et al (2018) A Comparative Assessment of Human and Chimpanzee iPSC-derived Cardiomyocytes with Primary Heart Tissues. Sci Rep 8 15312 PMID: 30333510
Sharma et al (2018) Stage-specific Effects of Bioactive Lipids on Human iPSC Cardiac Differentiation and Cardiomyocyte Proliferation. Sci Rep 8 6618 PMID: 29700394
Jiang et al (2018) An Ultrasensitive Calcium Reporter System via CRISPR-Cas9-Mediated Genome Editing in Human Pluripotent Stem Cells. iScience 9 27 PMID: 30368079
Piccini et al (2017) Adrenergic Stress Protection of Human iPS Cell-Derived Cardiomyocytes by Fast Kv7.1 Recycling. Front Physiol 8 705 PMID: 28959214
Rebecca L et al (2019) Wnt family member 4 (WNT4) and WNT3A activate cell-autonomous Wnt signaling independent of porcupine O-acyltransferase or Wnt secretion. J Biol Chem 294 19950-19966 PMID: 31740580
Kumi et al (2019) Engineering of human cardiac muscle electromechanically matured to an adult-like phenotype. Nat Protoc 14 2781-2817 PMID: 31492957
Fan et al (2019) Long-Term Stability and Differentiation Potential of Cryopreserved cGMP-Compliant Human Induced Pluripotent Stem Cells. Int J Mol Sci 21 PMID: 31877913
Nigmatullina et al (2017) Id2 controls specification of Lgr5+ intestinal stem cell progenitors during gut development. EMBO J 36 869 PMID: 28077488
Mark et al (2020) Reengineering an Antiarrhythmic Drug Using Patient hiPSC Cardiomyocytes to Improve Therapeutic Potential and Reduce Toxicity. Cell Stem Cell 27 813-821.e6 PMID: 32931730
Melanie et al (2020) Wnt regulates amino acid transporter Slc7a5 and so constrains the integrated stress response in mouse embryos. EMBO Rep 21 e48469 PMID: 31789450
Yoav et al (2020) Systematic Comparison of High-throughput Single-Cell and Single-Nucleus Transcriptomes during Cardiomyocyte Differentiation. Sci Rep 10 1535 PMID: 32001747
Andrew R et al (2020) Modeling polymorphic ventricular tachycardia at rest using patient-specific induced pluripotent stem cell-derived cardiomyocytes. EBioMedicine 60 103024 PMID: 32980690
Hui et al (2020) 16p11.2 microdeletion imparts transcriptional alterations in human iPSC-derived models of early neural development. Elife 9 PMID: 33169669
Nilesh J et al (2020) The role of cathepsin D in the pathophysiology of heart failure and its potentially beneficial properties: a translational approach. Eur J Heart Fail 22 2102-2111 PMID: 31797504
Walter C et al (2020) Accelerated differentiation of human pluripotent stem cells into neural lineages via an early intermediate ectoderm population. Stem Cells 38 1400-1408 PMID: 32745311
Hui et al (2020) Metabolic Maturation Media Improve Physiological Function of Human iPSC-Derived Cardiomyocytes. Cell Rep 32 107925 PMID: 32697997
Nathalie et al (2020) 4,4'-Diisothiocyanato-2,2'-Stilbenedisulfonic Acid (DIDS) Modulates the Activity of KCNQ1/KCNE1 Channels by an Interaction with the Central Pore Region. Cell Physiol Biochem 54 321-332 PMID: 32259418
Yong et al (2021) A Comparative Assessment of Marker Expression Between Cardiomyocyte Differentiation of Human Induced Pluripotent Stem Cells and the Developing Pig Heart. Stem Cells Dev 30 374-385 PMID: 33599158
Alain et al (2021) Oxygen Is an Ambivalent Factor for the Differentiation of Human Pluripotent Stem Cells in Cardiac 2D Monolayer and 3D Cardiac Spheroids. Int J Mol Sci 22 PMID: 33440843
Kenneth R et al (2021) Isolation of human ESC-derived cardiac derivatives and embryonic heart cells for population and single-cell RNA-seq analysis. STAR Protoc 2 100339 PMID: 33644774
David E et al (2021) Functional dynamic genetic effects on gene regulation are specific to particular cell types and environmental conditions. Elife 10 PMID: 33988505
Matthew et al (2021) Dynamic effects of genetic variation on gene expression revealed following hypoxic stress in cardiomyocytes. Elife 10 PMID: 33554857
Joseph C et al (2021) Massive expansion and cryopreservation of functional human induced pluripotent stem cell-derived cardiomyocytes. STAR Protoc 2 100334 PMID: 33615277
Ha Neui et al (2021) The thrombin receptor links brain derived neurotrophic factor to neuron cholesterol production, resiliency and repair after spinal cord injury. Neurobiol Dis 152 105294 PMID: 33549720
Rudolf A et al (2021) Selenoprotein DIO2 Is a Regulator of Mitochondrial Function, Morphology and UPRmt in Human Cardiomyocytes. Int J Mol Sci 22 PMID: 34769334
Nibaldo C et al (2021) Selective Surface and Intraluminal Localization of Wnt Ligands on Small Extracellular Vesicles Released by HT-22 Hippocampal Neurons. Front Cell Dev Biol 9 735888 PMID: 34722516
Rostovskaya et al (2019) Capacitation of human naïve pluripotent stem cells for multi-lineage differentiation. Development 146 PMID: 30944104
Ward and Gilad (2019) A generally conserved response to hypoxia in iPSC-derived cardiomyocytes from humans and chimpanzees. Elife 8 PMID: 30958265
Liang et al (2019) Canonical Wnt signaling promotes pacemaker cell specification of cardiac mesodermal cells derived from mouse and human embryonic stem cells. Stem Cells 38 352 PMID: 31648393
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Reviews for Wnt-C59
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Pancreatic cancer cells were incubated for pretreated for 2 hours with WNT-C59 followed by conventional chemotherapeutics. Wnt inhibition had an additive effect on cancer cell’s viability upon 3 days of treatment.
Literature in this Area
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