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Submit ReviewA 83-01
Description: Selective inhibitor of TGF-βRI, ALK4 and ALK7
Chemical Name: 3-(6-Methyl-2-pyridinyl)-N-phenyl-4-(4-quinolinyl)-1H-pyrazole-1-carbothioamide
Purity: ≥98% (HPLC)
Biological Activity for A 83-01
A 83-01 is a potent inhibitor of TGF-β type I receptor ALK5 kinase, type I activin/nodal receptor ALK4 and type I nodal receptor ALK7 (IC50 values are 12, 45 and 7.5 nM respectively). A 83-01 blocks phosphorylation of Smad2 and inhibits TGF-β-induced epithelial-to-mesenchymal transition. Only weakly inhibits ALK-1, -2, -3, -6 and MAPK activity. More potent than SB 431542 (Cat. No. 1614). A 83-01 inhibits differentiation of rat induced pluripotent stem cells (riPSCs) and increases clonal expansion efficiency. Helps maintain homogeneity and long-term in vitro self-renewal of human iPSCs. Also promotes neural differentiation of hPSCs as part of a chemical cocktail.
A 83-01 synthesized to Ancillary Material Grade also available.
For more information about how A 83-01 may be used, see our protocol: Converting Fibroblasts into Cardiomyocytes (9C Cocktail)
Technical Data for A 83-01
| M. Wt | 421.52 |
| Formula | C25H19N5S |
| Storage | Store at -20°C |
| Purity | ≥98% (HPLC) |
| CAS Number | 909910-43-6 |
| PubChem ID | 16218924 |
| InChI Key | HIJMSZGHKQPPJS-UHFFFAOYSA-N |
| Smiles | S=C(NC5=CC=CC=C5)N(N=C3C4=NC(C)=CC=C4)C=C3C2=CC=NC1=CC=CC=C12 |
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 A 83-01
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 21.08 | 50 |
Preparing Stock Solutions for A 83-01
The following data is based on the product molecular weight 421.52. 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 |
|---|---|---|---|
| 0.5 mM | 4.74 mL | 23.72 mL | 47.45 mL |
| 2.5 mM | 0.95 mL | 4.74 mL | 9.49 mL |
| 5 mM | 0.47 mL | 2.37 mL | 4.74 mL |
| 25 mM | 0.09 mL | 0.47 mL | 0.95 mL |
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Product Datasheets for A 83-01
References for A 83-01
References are publications that support the biological activity of the product.
Tojo et al (2005) The ALK5 inhibitor A-83-01 inhibits smad signaling and epithelial-to-mesenchymal transition by transforming growth factor-β. Cancer.Sci. 96 791 PMID: 16271073
Hoberg et al (2008) Attachment to laminin-111 facilitates transforming growth factor β-induced expression of matrix metalloproteinase-2 in synovial fibroblasts. Ann.Rheum.Dis. 66 446 PMID: 17124250
Li et al (2009) Generation of rat and human induced pluripotent stem cells by combining genetic reprogramming and chemical inhibitors. Cell Stem Cell 4 16 PMID: 19097958
Sato et al (2015) SnapShot: Growing Organoids from Stem Cells. Cell 161 1700 PMID: 26091044
Mahe et al (2014) Establishment of gastrointestinal epithelial organoids Curr.Protoc.Mouse Biol. 3 217 PMID: 25105065
Bartfeld et al (2015) In vitro expansion of human gastric epithelial stem cells and their responses to bacterial infection. Gastroenterology 148 126 PMID: 25307862
Lancaster et al (2015) Generation of Cerebral Organoids from Human Pluripotent Stem Cells Nat.Protoc. 9 2329 PMID: 25188634
Jung et al (2011) Isolation and in vitro expansion of human colonic stem cells. Nat.Med. 17 1225 PMID: 21892181
Boj et al (2015) Organoid models of human and mouse ductal pancreatic cancer. Cell 160 324 PMID: 25557080
Karthaus et al (2014) Identification of multipotent luminal progenitor cells in human prostate organoid cultures. Cells 159 163 PMID: 25201529
Koehler et al (2014) 3D mouse embryonic stem cell culture for generating inner ear organoids. Nat.Protoc. 9 1229 PMID: 24784820
Chen et al (2019) Chemically defined neural conversion of human pluripotent stem cells. Methods Mol.Biol. 1919 59 PMID: 30656621
If you know of a relevant reference for A 83-01, please let us know.
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Keywords: A 83-01, A 83-01 supplier, A83-01, Selective, inhibitors, inhibits, TGF-βRI, TGF-β, TGF-betaRI, TGFbRI, TGFbR1, tgf-b1ALK4, ALK7, ALK, Receptors, Activin, Receptor-like, Kinase, Serine/Threonine, Kinases, RSTKs, Transforming, Growth, Factor, Beta, A8301, stem, cells, growth, factors, organoids, diffe, TGF-beta, BMP, and, Other, Stem, Cell, Proliferation, Organoids, Neural, Cells, 2939, Tocris Bioscience
84 Citations for A 83-01
Citations are publications that use Tocris products. Selected citations for A 83-01 include:
Rostovskaya et al (2019) Capacitation of human naïve pluripotent stem cells for multi-lineage differentiation. Development 146 PMID: 30944104
Peterson et al (2019) Activating a Reserve Neural Stem Cell Population In Vitro Enables Engraftment and Multipotency after Transplantation. Stem Cell Reports 12 680 PMID: 30930245
Saito et al (2019) Establishment of Patient-Derived Organoids and Drug Screening for Biliary Tract Carcinoma. Cell Rep 27 1265 PMID: 31018139
Mazzucchelli et al (2019) Establishment and Morphological Characterization of Patient-Derived Organoids from Breast Cancer. Biol Proced Online 21 12 PMID: 31223292
Lindesmith et al (2019) Sera Antibody Repertoire Analyses Reveal Mechanisms of Broad and Pandemic Strain Neutralizing Responses after Human Norovirus Vaccination. Immunity 50 1530 PMID: 31216462
Ranganathan et al (2019) Evaluating Shigella flexneri Pathogenesis in the Human Enteroid Model. Infect Immun 87 PMID: 30642900
Wosen et al (2019) Human Intestinal Enteroids Model MHC-II in the Gut Epithelium. Front Immunol 10 1970 PMID: 31481960
Chen et al (2019) Chemically Defined Neural Conversion of Human Pluripotent Stem Cells Methods Mol.Biol. 1919 59 PMID: 30656621
Liu et al (2018) CRISPR-based chromatin remodeling of the endogenous Oct4 or Sox2 locus enables reprogramming to pluripotency. Cell Stem Cell. 22 252 PMID: 29358044
Peng et al (2018) Inflammatory Cytokine TNFα Promotes the Long-Term Expansion of Primary Hepatocytes in 3D Culture. Cell 175 1607 PMID: 30500539
Rajamani et al (2018) Super-Obese Patient-Derived iPSC Hypothalamic Neurons Exhibit Obesogenic Signatures and Hormone Responses. Cell Stem Cell 22 698 PMID: 29681516
Lynch et al (2018) Submucosal Gland Myoepithelial Cells Are Reserve Stem Cells That Can Regenerate Mouse Tracheal Epithelium. Cell Stem Cell 22 653 PMID: 29656941
Wang et al (2016) Anti-tumor activity of SL4 against breast cancer cells: induction of G2/M arrest through modulation of the MAPK-dependent p21 signaling pathway. Sci Rep 6 36486 PMID: 27819344
Han et al (2022) FOXA2 drives lineage plasticity and KIT pathway activation in neuroendocrine prostate cancer. Cancer Cell 40 1306 PMID: 36332622
He et al (2022) Optimized human intestinal organoid model reveals interleukin-22-dependency of paneth cell formation. Cell Stem Cell 29 1333 PMID: 36002022
Mou et al (2016) Dual SMAD Signaling Inhibition Enables Long-Term Expansion of Diverse Epithelial Basal Cells Cell: Stem Cell 19 217 PMID: 27320041
Foulke-Abel et al (2016) Human Enteroids as a Model of Upper Small Intestinal Ion Transport Physiology and Pathophysiology. Nat Protoc 150 638 PMID: 26677983
Drost et al (2016) Organoid culture systems for prostate epithelial and cancer tissue. Proc Natl Acad Sci U S A 11 347 PMID: 26797458
Zamudio et al (2016) Inhibition of TGFβ cell signaling for limbal explant culture in serumless, defined xeno-free conditions. Exp Eye Res 145 48 PMID: 26554938
Mousavizadeh et al (2016) Angiopoietin-like 4 promotes angiogenesis in the tendon and is increased in cyclically loaded tendon fibroblasts. J Physiol 594 2971 PMID: 26670924
Weeber et al (2015) Preserved genetic diversity in organoids cultured from biopsies of human colorectal cancer metastases. Hum Mol Genet 112 13308 PMID: 26460009
Mattis et al (2015) HD iPSC-derived neural progenitors accumulate in culture and are susceptible to BDNF withdrawal due to glutamate toxicity. Exp Cell Res 24 3257 PMID: 25740845
Bras et al (2015) TGFβ loss activates ADAMTS-1-mediated EGF-dependent invasion in a model of esophageal cell invasion. Nat Genet 330 29 PMID: 25064463
Liao et al (2015) Targeted disruption of DNMT1, DNMT3A and DNMT3B in human embryonic stem cells. Cell 47 469 PMID: 25822089
Boj et al (2015) Organoid models of human and mouse ductal pancreatic cancer. Cell 160 324 PMID: 25557080
Huch et al (2015) Long-term culture of genome-stable bipotent stem cells from adult human liver. Nature 160 299 PMID: 25533785
Tsankov et al (2015) Transcription factor binding dynamics during human ES cell differentiation. Stem Cell Reports 518 344 PMID: 25693565
Kido et al (2015) CPM Is a Useful Cell Surface Marker to Isolate Expandable Bi-Potential Liver Progenitor Cells Derived from Human iPS Cells. Inflamm Bowel Dis 5 508 PMID: 26365514
Sibony et al (2015) Microbial Disruption of Autophagy Alters Expression of the RISC Component AGO2, a Critical Regulator of the miRNA Silencing Pathway. Proc Natl Acad Sci U S A 21 2778 PMID: 26332312
Yang et al (2015) Heightened potency of human pluripotent stem cell lines created by transient BMP4 exposure. Stem Cell Reports 112 E2337 PMID: 25870291
Nantasanti et al (2015) Disease Modeling and Gene Therapy of Copper Storage Disease in Canine Hepatic Organoids. Stem Cell Res 5 895 PMID: 26455412
Li et al (2014) PMA induces SnoN proteolysis and CD61 expression through an autocrine mechanism. Cell Signal 26 1369 PMID: 24637302
Jeong et al (2023) ERdj5 protects goblet cells from endoplasmic reticulum stress-mediated apoptosis under inflammatory conditions Exp Mol Med PMID: 36759578
Tata et al (2018) Myoepithelial Cells of Submucosal Glands Can Function as Reserve Stem Cells to Regenerate Airways after Injury. Cell Stem Cell 22 668 PMID: 29656943
Levardon et al (2018) Expansion of Airway Basal Cells and Generation of Polarized Epithelium. Bio Protoc 8 PMID: 30009215
Yip et al (2018) Colon organoid formation and cryptogenesis are stimulated by growth factors secreted from myofibroblasts. PLoS One 13 e0199412 PMID: 29928021
Yakoub and Sadek (2018) Development and Characterization of Human Cerebral Organoids: An Optimized Protocol. Cell Transplant 27 393 PMID: 29749250
Kashfi et al (2018) Morphological alterations of cultured human colorectal matched tumour and healthy organoids. Oncotarget 9 10572 PMID: 29535828
Roper et al (2018) Colonoscopy-based colorectal cancer modeling in mice with CRISPR-Cas9 genome editing and organoid transplantation. Nat Protoc 13 217 PMID: 29300388
Biffi et al (2018) IL-1-induced JAK/STAT signaling is antagonized by TGF-beta to shape CAF heterogeneity in pancreatic ductal adenocarcinoma. Cancer Discov PMID: 30366930
Sheng et al (2018) A stably self-renewing adult blood-derived induced neural stem cell exhibiting patternability and epigenetic rejuvenation. Nat Commun 9 4047 PMID: 30279449
Bayrer et al (2018) LRH-1 mitigates intestinal inflammatory disease by maintaining epithelial homeostasis and cell survival. Nat Commun 9 4055 PMID: 30305617
Li et al (2018) COX-2-PGE2 Signaling Impairs Intestinal Epithelial Regeneration and Associates with TNF Inhibitor Responsiveness in Ulcerative Colitis. EBioMedicine 36 497 PMID: 30190207
Zhang et al (2016) Pharmacological reprogramming of fibroblasts into neural stem cells by signaling-directed transcriptional activation. Cell Stem Cell 18 PMID: 27133794
Chen et al (2021) A versatile polypharmacology platform promotes cytoprotection and viability of human pluripotent and differentiated cells. Nat.Methods 18 528 PMID: 33941937
Stanifer et al (2020) Critical Role of Type III Interferon in Controlling SARS-CoV-2 Infection in Human Intestinal Epithelial Cells Cell Rep 32 107863 PMID: 32610043
Post et al (2020) Snake venom gland organoids. Cell 180 233 PMID: 31978343
Willigen et al (2019) Folding-function relationship of the most common cystic fibrosis-causing CFTR conductance mutants. Life Sci Alliance 2 PMID: 30659068
Barros-Silva et al (2018) Single-Cell Analysis Identifies LY6D as a Marker Linking Castration-Resistant Prostate Luminal Cells to Prostate Progenitors and Cancer. Cell Rep 25 3504 PMID: 30566873
Roe et al (2017) Enhancer Reprogramming Promotes Pancreatic Cancer Metastasis. Cell 170 875 PMID: 28757253
Yang et al (2017) Establishment of mouse expanded potential stem cells. Nature 550 393 PMID: 29019987
Vermilyea et al (2017) Induced Pluripotent Stem Cell-Derived Dopaminergic Neurons from Adult Common Marmoset Fibroblasts. Stem Cells Dev 26 1225 PMID: 28635509
Pietz et al (2017) Immunopathology of childhood celiac disease-Key role of intestinal epithelial cells. PLoS One 12 e0185025 PMID: 28934294
Ma et al (2017) Organoid culture of human prostate cancer cell lines LNCaP and C4-2B. Am J Clin Exp Urol 5 25 PMID: 29181435
Roper et al (2017) In vivo genome editing and organoid transplantation models of colorectal cancer and metastasis. Nat Biotechnol 35 569 PMID: 28459449
Ruetz et al (2017) Constitutively Active SMAD2/3 Are Broad-Scope Potentiators of Transcription-Factor-Mediated Cellular Reprogramming. Cell Stem Cell 21 791 PMID: 29174331
Guo et al (2017) Epigenetic resetting of human pluripotency. Development 144 2748 PMID: 28765214
Dai et al (2015) Maintenance and neuronal differentiation of chicken induced pluripotent stem-like cells. Stem Cells Int 2014 182737 PMID: 25610469
Tan et al (2015) Amnion cell mediated immune modulation following bleo. challenge: controlling the regulatory T cell response. Stem Cell Res Ther 6 8 PMID: 25634246
Zhao et al (2015) High-efficiency reprogramming of fibroblasts into cardiomyocytes requires suppression of pro-fibrotic signalling. Nat Commun 6 8243 PMID: 26354680
Corritore et al (2014) β-Cell differentiation of human pancreatic duct-derived cells after in vitro expansion. Cell Cycle 16 456 PMID: 25437872
Boilàve et al (2013) Immunosurveillance against tetraploidization-induced colon tumorigenesis. Proc Natl Acad Sci U S A 12 473 PMID: 23324343
Kearns et al (2013) Generation of organized anterior foregut epithelia from pluripotent stem cells using small molecules. PLoS One 11 1003 PMID: 23917481
Schwank et al (2013) Generation of BAC transgenic epithelial organoids. Cell Reprogram 8 e76871 PMID: 24204693
Telugu et al (2011) Porcine induced pluripotent stem cells analogous to naïve and primed embryonic stem cells of the mouse. Int J Dev Biol 54 1703 PMID: 21305472
Raghavan et al (2021) Microenvironment drives cell state, plasticity, and drug response in pancreatic cancer. Cell 184 6119 PMID: 34890551
Tristan et al (2021) Robotic high-throughput biomanufacturing and functional differentiation of human pluripotent stem cells. Stem Cell Rep 16 3076 PMID: 34861164
Duan et al (2021) An airway organoid-based screen identifies a role for the HIF1α-glycolysis axis in SARS-CoV-2 infection. Cell Rep. 37 109920 PMID: 34731648
Kazi et al (2021) Global phosphoproteomics reveal CDK suppression as a vulnerability to KRas addiction in pancreatic cancer. Clin Cancer Res 27 4012 PMID: 33879459
Berkers et al (2019) Rectal Organoids Enable Personalized Treatment of Cystic Fibrosis. Cell Rep 26 1701 PMID: 30759382
Kanitz et al (2019) Conserved regulation of RNA processing in somatic cell reprogramming. BMC Genomics 20 100 PMID: 30704403
Muraoka et al (2019) Role of cyclooxygenase-2-mediated prostaglandin E2-prostaglandin E receptor 4 signaling in cardiac reprogramming. Nat Commun 10 674 PMID: 30787297
Huang et al (2017) Zfp281 is essential for mouse epiblast maturation through transcriptional and epigenetic control of Nodal signaling. Elife 6 PMID: 29168693
Mulas et al (2017) NODAL Secures Pluripotency upon Embryonic Stem Cell Progression from the Ground State. Stem Cell Reports 9 77 PMID: 28669603
Filippini et al (2019) Immunoevolution of mouse pancreatic organoid isografts from preinvasive to metastatic disease. Sci Rep 9 12286 PMID: 31439856
Tanigawa et al (2019) Activin Is Superior to BMP7 for Efficient Maintenance of Human iPSC-Derived Nephron Progenitors. Stem Cell Reports 13 322 PMID: 31378669
Crowell et al (2019) Expansion of Luminal Progenitor Cells in the Aging Mouse and Human Prostate. Cell Rep 28 1499 PMID: 31390564
Jee et al (2019) Development of Collagen-Based 3D Matrix for Gastrointestinal Tract-Derived Organoid Culture. Stem Cells Int 2019 8472712 PMID: 31312220
Genovese (2017) Enhanced Development of Skeletal Myotubes from Porcine Induced Pluripotent Stem Cells. Sci Rep 7 41833 PMID: 28165492
Okiyoneda et al (2013) Mechanism-based corrector combination restores δF508-CFTR folding and function. Nat Chem Biol 9 444 PMID: 23666117
O'Malley et al (2013) High-resolution analysis with novel cell-surface markers identifies routes to iPS cells. Nature 499 88 PMID: 23728301
Yanagida et al (2013) An in vitro expansion system for generation of human iPS cell-derived hepatic progenitor-like cells exhibiting a bipotent differentiation potential. PLoS One 8 e67541 PMID: 23935837
Hirschhorn et al (2012) Differential regulation of Smad3 and of the type II transforming growth factor-β receptor in mitosis: implications for signaling. PLoS One 7 e43459 PMID: 22927969
Kawamata and Ochiya (2010) Generation of genetically modified rats from embryonic stem cells. Nature 107 14223 PMID: 20660726
Do you know of a great paper that uses A 83-01 from Tocris? Please let us know.
Reviews for A 83-01
Average Rating: 4.8 (Based on 10 Reviews.)
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Works perfectly.
By
Toni Johansson on 04/01/2021
Assay Type: In Vitro
Species: Human
To grow primary basal cells
Works well with liver organoids.
By
Gautam Kok on 11/19/2020
Assay Type: In Vitro
Species: Human
Cell Line/Tissue: Liver organoids
Used in expansion medium for culturing liver organoids
It worked good.
By
Anonymous on 07/04/2020
Assay Type: In Vitro
Species: Mouse
Cell Line/Tissue: iPSC
Reprogramming media comprises of 3 μM CHIR99021 and 0.5 μM A-83-01.
The cells were then maintained in RM 15 days with fresh media every other day
For TGFB inhibition.
By
Anonymous on 06/25/2020
Assay Type: In Vitro
Species: Mouse
Cell Line/Tissue: Neural Stem Cells
Cells are treated with 1 mM A83-01 to inhibit canonical TGFB signaling
Neural Induction Conditions.
By
Anonymous on 03/22/2020
Assay Type: In Vitro
Species: Human
Cell Line/Tissue: H9
2 μM A83–01
To start reprogramming, cultures were switched to reprogramming medium (ES medium supplemented with 1 mM A83-01).
By
Anonymous on 12/04/2019
Assay Type: In Vitro
Species: Mouse
Cell Line/Tissue: ipsc
To start reprogramming, cultures were switched to reprogramming medium (ES medium supplemented with 10 mM Parnate, 3 mM Chir99021, 1 mM A83-01, and 10 mM Forskolin)
good for cell culture.
By
Anonymous on 10/08/2019
Assay Type: In Vivo
Species: Mouse
Cell Line/Tissue: ipsc
add to cell culture to do 3d culture
works great for TGFB inhibition.
By
Anonymous on 08/08/2019
Assay Type: In Vitro
Species: Human
used it to grow primary basal cells
for growing cells.
By
Anonymous on 02/28/2019
Assay Type: In Vitro
Species: Human
used it to grow human airway basal cells
A 83-01 Inhibit TGFb1-activated Cellular Fibrosis in Human Mϋller Cells.
By
Ying Yu on 01/08/2018
Assay Type: In Vitro
Species: Human
Cell Line/Tissue: Mϋller cells
Human MOI-M1 Mϋller cells seeded in tissue culture (TC)-treated plastic plate (BD). Serum starvation by DMEM medium supplemented with 1% FBS for 24h. Pretreated Human Mϋller cell with A83-01 at 0, 0.25, 0.5, 1 and 2uM for 2h. Then added 0-10 ng/mL TGFb1 for 48h. Picro-Sirius red staining, elution, and OD 540nm measurement for the fibrosis
Protocols for A 83-01
The following protocol features additional information for the use of A 83-01 (Cat. No. 2939).
Literature in this Area
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Stem Cell Research Product Guide
This product guide provides a background to the use of small molecules in stem cell research and lists over 200 products for use in:
- Self-renewal and Maintenance
- Differentiation
- Reprogramming
- Organoid Generation
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Stem Cells Scientific Review
Written by Kirsty E. Clarke, Victoria B. Christie, Andy Whiting and Stefan A. Przyborski, this review provides an overview of the use of small molecules in the control of stem cell growth and differentiation. Key signaling pathways are highlighted, and the regulation of ES cell self-renewal and somatic cell reprogramming is discussed. Compounds available from Tocris are listed.
Stem Cells Poster
Written by Rebecca Quelch and Stefan Przyborski from Durham University (UK), this poster describes the isolation of pluripotent stem cells, their maintenance in culture, differentiation, and the generation and potential uses of organoids.
Pathways for A 83-01
