Stemolecule™ SB431542

SB431542 is an inhibitor of the transforming growth factor-β 1 (TGFβ1) activin receptor-like kinases (ALKs). It is a selective and potent inhibitor of ALK-4, -5 and -7. SB431542 inhibits endogenous activin and TGFβ signaling without affecting more divergent BMP signaling utilizing ALK-1, -2, -3, and -6^1,2. SB431542 stimulates proliferation, differentiation, and sheet formation of endothelial cells derived from embryonic stem cells³.

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

Product Name: Stemolecule SB431542

Catalog Number: 04-0010-base

Size:

• 10 mg (Cat. No. 04-0010-10)
• 5 mg (Cat. No. 04-0010)
• 5 mg at 10 mM in DMSO (04-0010-05)

Alternate Name(s): 4-[4-(1,3-benzodioxol-5-yl)-5-pyridin-2-yl-1H-imidazol-2-yl]benzamide

Chemical Formula: C₂₂H₁₆N₄O₃

Molecular Weight: 384.4

CAS Number: 301836-41-9 (anhydrous)

Purity: Greater than 98 % by HPLC analysis

Formulation: White solid

Solubility: Reconstitute in DMSO to the desired concentration. For reconstitution instructions please reference product specifications sheet.

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 SB431542 was determined by HPLC analysis. The accurate mass was determined by mass spectrometry. Cellular toxicity of SB431542 was tested on mouse embryonic stem cells.

Specification Sheets:

• 04-0010 Specifications Sheet
• 04-0010-10 Specifications Sheet
• 04-0010-05 Specifications Sheet

Safety Data Sheets:

• 04-0010 and 04-0010-10 Safety Data Sheet (SDS)
• 04-0010-05 Safety Data Sheet (SDS)

1. Matsuyama, S., Iwadate, M., Kondo, M., Saitoh, M., Hanyu, A., Shimizu, K., Aburatani, H., Mishima, H.K., Imamura, T., Miyazono, K., Miyazawa, K. SB-431542 and Gleevec inhibit transforming growth factor-β-induced proliferation of human osteosarcoma cells. Cancer Res 63: 7791-7798 (2003).
2. Laping, N.J., Grygielko, E., Mathur, A., Butter, S., Bomberger, J., Tweed, C., Martin, W., Fornwald, J., Lehr, R., Harling, J., Gaster, L., Callahan, J.F., and Olson, B.A. Inhibition of transforming growth factor (TGF)-β1-induced extracellular matrix with a novel inhibitor of the TGF-β type I receptor kinase activity: SB-431542. Mol Pharmacol 62: 58-64 (2002).
3. Inman, G.J., Nicolás, F.J., Callahan, J.F., Harling, J.D., Gaster, L.M., Reith, A.D., Laping, N.J., and Hill, C.S. SB-431542 is a potent and specific inhibitor of transforming growth factor-β superfamily type I activin receptor-like kinase (ALK) receptors ALK4, ALK5, and ALK7. Mol Pharmacol 62: 65-74 (2002).
4. Watabe, T., Nishihara, A., Mishima, K., Yamashita, J., Shimizu, K., Miyazawa, K., Nishikawa, S., and Miyazono, K. TGFβ receptor kinase inhibitor enhances growth and integrity of embryonic stem cell-derived endothelial cells. J Cell Biol 163: 1303-1311 (2003).

Additional Publications

• Mazza NC; Shuck SC; Lin J: Moxley AM; Termini J; Cookson MR; Wilson MA. DJ-1 is not a deglycase and makes a modest contribution to cellular defense against methylglyoxal damage in neurons. J Neurochem 162:245 (2022).
• Seesankar GA; . Investigating Adenosine-to-Inosine RNA Editing in Rett Syndrome Neurons . Masters Thesis, University of Toronto : (2022).
• Lu V; Doan MT; Roy IJ; Torres A; Teitell MA;. Protocol for germ lineage differentiation of primed human pluripotent stem cells using chemically defined, nutrient-balanced media. Star Protocols 3:101568 (2022).
• Liang L ;Tian Y; Feng L; Wang C; Feng G; Stacey GN; Shyh-Change N; Wu J; Hu B; Li W: Hao J; Wang L; Wang Y. Single-cell transcriptomics reveals the cell fate transitions of human dopaminergic progenitors derived from hESCs. Stem Cell Res Therap 13:412 (2022).
• Lieberman R; Cortes LK; Gao G; Park H; Wang B; Jones PL; Hunter RB; Leonard JP; Barker RH. Human iPSC-derived astrocytes generated from donors with globoid cell leukodystrophy display phenotypes associated with disease. PLOS One 17:e0271360 (2022).
• Gonzàlez BJ; Zhao H; Niu J; Williams DJ; Lee J; Goulbourne CN' Xing Y; Wang Y' Oberholzer J; Blumenkrantz MH; Chen X; LeDuc CA; Chung WK; Colecraft HM; Gromada J; ShenY; Goland RS; Leibel RL; Egli D. Reduced calcium levels and accumulation of abnormal insulin granules in stem cell models of HNF1A deficiency. Commun Biology 5:779 (2022).
• Yang Y; Laterza V; StuartHT; Michielin F; Gagliano O; Urciuolo A; Elvassore N. Human Pluripotent Stem Cell-Derived Micropatterned Ectoderm Allows Cell Sorting of Meso-Endoderm Lineages. Front Bioeng Biotechnol 10:907159 (2022).
• Cohen B; McPhie D; Ren B; Garcia-Leon J; Verfaille C. SOX10 Expression Levels may be a Critical Mediator of White Matter Deficits in Schizophrenia. BioRivX https://doi.org/10.21203/rs.3.rs-1808873/v1: (2022).
• Wang T; Liu H; Itoh K; Oh S; Zhao L ;Murata D; Sesaki H; Hartung T; Na CH; Wang J. C9orf72 regulates energy homeostasis by stabilizing mitochondrial complex I assembly. Cell Metabolism 33:531-546.e9 (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).
• Khalili M; Zarebkohan A; Dianat-Moghadam H; Panahi M; Andre H; Alizadeh E. Corneal endothelial cell sheet bioengineering from neural crest cell-derived adipose stem cells on novel thermo-responsive elastin-mimetic dendrimers decorated with RGD. Chem Engr J 429:132523 (2022).
• Ressler AK. Reading the Disease Leaves: Signals, signatures and synchrony in neurodevelopmental disorders. Ph. D. Thesis, Columbia University : (2021).
• Hirata N; Yanada S; Yanagida S; OnonA; Yasuhiko Y; Kanda Y. Transforming Growth Factor Beta Promotes the Expansion of Cancer Stem Cells via S1PR3 by Ligand-Independent Notch Activation. Biol Pharmaceut Bull 45://doi.org/10.1248/bpb.b22-00112 (2022).
• Papes F; Camargo AP; de Souza GGS' Carvalho VMA; Szeto RA' LoMontagne E: Teixeira JR; Avansini SH; Sánchez-Sánchez SM; Nakahara TS; Santo SN; Wu W: Yao H; Araújo BMP; Velho PENF; Haddad GG; Muotri AR. Transcription Factor 4 loss-of-function is associated with deficits in progenitor proliferation and cortical neuron content. Nature Commun 13:2387 (2022).
• Lu V. The Role of Glutamine in Primed Human Pluripotent Stem Cell Fate. Ph.D. Theses, University of California, Los Angeles : (2022).
• Moussa A; Yasmine H; Manaphe N; Ali G; Maacha S; Shin KC; Ltaief SM; Gupta V; Tong Y; Bonraj J; Salloum-Asfar S; Mansour S; Al-Shaban FA; Kim H-G; Stanton LW; Grivel J-C; Abdulla SA; Al-Shammari AR; Park Y. Single Extracellular Vesicle Analysis Using Flow Cytometry for Neurological Disorder Biomarkers. Front Integrtive Neuroscience May 2022:DOI:10.3389/fnint.2022.879832 (2022).
• Bergström P; Trybala E; Eriksson CE; Johansson M; Satir TM; Widehn S; Fruhwürth S; Michno W; Nazir FH; Hanrieder J; Paludan SR; Agholme L; Zetterberg H; Bergström T. Herpes Simplex Virus 1 and 2 Infections during Differentiation of Human Cortical Neurons. Viruses 13:2072 (2021).
• Mok RSF. Morphology and Connectivity Impairments in Rett Syndrome Human Stem Cell-Derived Neurons. Ph. D. Thesis, Univ of Toronto : (2020).
• EMBO Mol Med. Pharmacological reversal of synaptic and network pathology in human MECP2‐KO neurons and cortical organoids. e12523: (2020).
• Mou Y; Dong Y; Chen Z; Denton KR; Duff MO; Blackstone C; Zhang S-C; Li X-J. Impaired lipid metabolism in astrocytes underlies degeneration of cortical projection neurons in hereditary spastic paraplegia. Acto Neuropathologica Commun 8:214 (2020).
• Choi SY; Lee J-H; Chung A-Y; Jo Y; Shin J-h; Park H-C; Kim H; Lopez-Gonzalez R; Ryu JR; Sun W. Prevention of mitochondrial impairment by inhibition of protein phosphatase 1 activity in amyotrophic lateral sclerosis. Cell Death Disease 11:888 (2020).
• Sun X-J; Li Ming-Xing; Gong C-Z; Chen J; Nasb M; Shah ZA; Rehan M; Li Y-J; Chen C. Temporal expression profiles of lncRNA and mRNA in human embryonic stem cell-derived motor neurons during differentiation. Peer J ://doi.org/10.7717/peerj.10075 (2020).
• Barbar L; Rusielewica T; Zimmer M; Kalpana K; Fossati V. Isolation of Human CD49f+ Astrocytes and In Vitro iPSC-Based Neurotoxicity Assays. STAR Protocols :doi.org/10.1016/j.xpro.2020.100172 (2020).
• Sato T; Higashioka K; Kakurai H; Yamamoto T; Goshima N; Ueno M; Sotozono C. Core Transcription Factors Promote Induction of PAX3-Positive Skeletal Muscle Stem Cells. Stem Cell Rep 13:352-365 (2019).
• Zhu Z; Mesci P Bernatchez JA Gomple RC; Wang X; Schafer ST; Wettersten HI; Beck S; Clarck AE; Wu Q; Prager BC; Kim LJY; Dhanwani R; Sharma S; Garancher A: WEis SM; Mack SC; Negraes PD; Trujillo CA; Penalva LO; Feng J; Lan Z; Zhang R; Wessel AW; Dhawan S; Diamond MS; Chen CC; Wechsler-Reya RJ; Gage FH; Hu H; Siqueira-Neto JL; Muotri AR; Gheresh DA; Rich JN. Zika Virus Targets Glioblastoma Stem Cells through a SOX2-Integrin α_vβ₅ Axis. Cell Stem Cell 26:187-204.E10 (2020).
• Trus I; Berube N; Jiang P; Rak J; Gerdts V; Karniychuk U. Zika Virus with Increased CpG Dinucleotide Frequencies Shows Oncolytic Activity in Glioblastoma Stem Cells. Viruses 12:579 (2020).
• Shafa M; Walsh T; Panchalingam KM; Richardson T; Menendez L; Tian X; Babu SS; Dadgar S; Beller J; Yang F; Baghbaderani BA. Long-Term Stability and Differentiation Potential of Cryopreserved cGMP-Compliant Human Induced Pluripotent Stem Cells. Int J Molecular Sci 21:108 (2020).
• Chu J; Fitzgerald ML; Sehgal M; Manley W; Fitzgerald S; Naung H; Goldberg EM; Anderson SA. Enhanced maturation of human stem cell derived interneurons by mTOR activation . bioRxiv :dx.doi.org/10.1101/777714 (2019).
• Yuva-Aydemir Y; Almeida S; Krishnan G; Gendron TF; Goa F-B. AFF2/FMR2 regulates expression of expanded GGGGCC repeat-containing C9ORF72 allele in ALS/FTD. Nature Commun 10:5466 (2019).
• Leitner D; Ramamoorthy M; Dejosez M; Zwaka TP. Immature mDA Neurons Ameliorate Motor Deficits in a 6-OHDA Parkinson's Disease Mouse Model and are Functional after Cryopreservation. Stem Cell Res in press:doi.org/10.1016/j.scr.2019.101617 (2019).
• Nagaraja S; Quezada MA; Gillespie SM; Arzt M; Lennon JJ; Woo PJ; Hovestadt V; Kambhampati M; Filbin MG; Suva ML; Nazarian J; Monje M. Histone Variant and Cell Context Determine H3K27M Reprogramming of the Enhancer Landscape and Oncogenic State. Molecular Cell 76:1-16 (2019).
• Durens M; Nestor J; Herold K Niescier RF; Lunden FW; Phillips AW; Lin Y-C; Nestor MW. High-content interrogation of human induced pluripotent stem cell-derived cortical organoid platforms. bioRxiv http://dx.doi.org/10.1101/697623. : (2019).
• de Souza JS; Ferreira DR; Herai R; Carromeu C; Torres LB; Araujo BHS; Cugola F; Maciel RMB; Muotri AR; Giannocco G. Altered Gene Expression of Thyroid Hormone Transporters and Deiodinases in iPS MeCP2-Knockout Cells-Derived Neurons. Molecular Neurobiol in press:https://doi.org/10.1007/s12035-019-01645-2 (2019).
• Wang Y; Gao J; Wang H; Wang M; Wen Q; Guo J; Su P; Shi L; Zhou W; Zhou J. R-spondin2 promotes hematopoietic differentiation of human pluripotent stem cells by activating TGF beta signaling. Stem Cell Res Therap 10:136 (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).
• Zhang Y; Zhang Y; Li M; Mend F; Yu Z; Chen Y; Cui G. Combination of SB431542, CHIR99021 and PD0325901 has a synergic effect on abrogating valproic acid‑induced epithelial‑mesenchymal transition and stemness in HeLa, 5637 and SCC‑15 cells. Oncol Rep In Press:https://doi.org/10.3892/or.2019.7088 (2019).
• Graß T. Modeling familial Alzheimer's disease utilizing gene targeted human induced pluripotent stem cells. Doctoral Thesis, Freie Univerität Berlin : (2018).
• Rosa-Fernandes L; Rodrigues Cugola F; Baldino Russo F; Kawahara R; de Melo Freire CC; Corrêa Leite PE; Bassi Stern AC; Angeli CB; Leal de Oliverira DB; Rezende Melo S; de Andrade Zanotto PM; Durigon EL; Larsen MR; Baleeiro Beltrão-Braga PC; Palmisano G. Zika Virus Impairs Neurogenesis and Synaptogenesis Pathways in Human Neural Stem Cells and Neurons. Frontiers Cell Neurosci 13:64 (2019).
• LI S; Zhang H; Wang A; Liu Y; Yue F; Abulati X; Zhang C; Li L. Differentiation of adult human retinal pigment epithelial cells into dopaminergic-like cells in vitro and in the recipient monkey brain. Molecular Med 25:9 (2019).
• Wadhwani AR; Affaneh A; Van Gulden S; Kessler JA. Neuronal Apolipoprotein E4 increases cell death and p‐tau release in Alzheimer's disease. Ann Neurol doi: 10.1002/ana.25455.: (2019).
• Winston TS; Suddhapas K; Wang C; Ramos R; Soman P; Ma Z. Serum-Free Manufacturing of Mesenchymal Stem Cell Tissue Rings Using Human-Induced Pluripotent Stem Cells. Stem Cells Int Article ID: 5654324:11 pages (2019).
• Wu C; Watts ME; Rubin LL. MAP4K4 Activation Mediates Motor Neuron Degeneration in Amyotrophic Lateral Sclerosis. Cell Reports 26:1143-1156.e5 (2019).
• van Rhijn, J-R. The role of FOXP2 in striatal circuitry. Ph.D. Thesis, Radboud University Nijmegen : (2019).
• Sun X; Song J; Huang H; Chen H; Qian K. Modeling hallmark pathology using motor neurons derived from the family and sporadic amyotrophic lateral sclerosis patient-specific iPS cells. Stem Cell Res Therapy 9:315 (2018).
• Javed AO; Li Y; Muffat J; Su K-C; Cohen MA; Lungjangwa T; Auborg P; Cheeseman IM; Jaenisch R. Microcephaly Modeling of Kinetochore Mutation Reveals a Brain-Specific Phenotype. Cell Rep 25:368-382.e5 (2018).
• Whitworth DJ; Limnios IJ; Gauthier M-E; Weeratunga P; Ovchinnikov DA; Baillie G; Grimmond SM; Graves JAM; Wolvetang EJ. Platypus Induced Pluripotent Stem Cells: the Unique Pluripotency Signature of a Monotreme . BioRXiv 43306: (2018)
• Chhabra S; Liu L; Goh R; WarmflashA. The timing of signaling events in the BMP, WNT, and Nodal cascade determines self-organized fate patterning in human gastruloids. bioRxiv 2018:http://dx.doi.org/10.1101/440164 (2018).
• Chen Z;l Ren X; Xu X; Zhang Z; Hui Y; Liu Z; Shi L; Fang Y; Ma L; Liu T; Terheyden-Keighley D; Liu L; Zhang X. Genetic Engineering of Human Embryonic Stem Cells for Precise Cell Fate Tracing during Human Lineage Development. Stem Cell Rep in press:https://doi.org/10.1016/j.stemcr.2018.09.014 (2018).
• Peng Y; Xie M; Duan X; Hu L; Yu J; Zeng S; Wange Y; Ouang Q; Lu G; Lin G; Sun Y. Generation of a luciferase-expressing human embyronic stem cell line: NERCe002-A-2. Stem Cell Research doi.org/10.1016/j.scr.2018.02.010: (2018).
• Kogut I; McCarthy SM; Pavlova M; Astling DP; Chen Xx; Jakimenko A; Jones KL; Getahun A; Cambier JC; Pasmooij AMG; Jonkman MF; Roop DR; Bilousova G. High-efficiency RNA-based reprogramming of human primary fibroblasts. Nature Communications 9:745 (2018).
• Schaefer SA; Higashi A; Loomis B; Schrepfer T; Wan G; Corfas G; Dressler GR; Duncan RK. From Otic Induction to Hair Cell Production: Pax2^EGFPCell Line Illuminates Key Stages of Development in Mouse Inner Ear Organoid Model. Stem Cells Development 27:237-251 (2018).
• Lee H; Haller C; Manneville C; Doll T; Fruh I; Gubser Keller C; Richards SM; Ibig-Rehm Y; Patoor M; Goette M; Bouchez LC; Mueller M. Identification of Small Molecules Which Induce Skeletal Muscle Differentiation in Embryonic Stem Cells via Activation of the Wnt and Inhibition of Smad2/3 and Sonic Hedgehog Pathways. Stem Cells 34:299-310 (2016).
• Wang Y; Qin J; Wang S; Zhanfg W; Duan J; Zhang J; Wang X; Yan F; Chang M; Liu X; Feng B; Liu J; Pei X; Pei X. Conversion of human gastric epithelial cells to multipotent endodermal progenitors using defined small molecules. Cell Stem Cell 19:449 (2016).
• Koehler KR; Ine J; Longworth-Mills E; Liu X-P; Lee J; Holt JR; Hashino E. Generation of inner ear organoids with functional hair cells from pluripotent stem cells. Nat Biotechnol 35:583-589 (2017).
• Ogaki S; Morooka M; Otera K; Kume S. A cost-effective system for differentiation of intestinal epithelium from human induced pluripotent cells. Sci Rep 5:17297 (2015).
• Pollen AA; Nowakowski TJ; Shuga J; Wang X; Leyrat AA; Lui JH; Li Z; Szpankowski L; Fowler B; Chen P; Ramalingam N; Sun G; Thu M; Norris M; Lebofsky R; Toppani D; Kemp DW; Wong M; Clerkson B; Jones BN; Wu S; Knutsson L; Alvaredo B; Wang J; Weaver LS; May AP; Jones RC; Unger MA; Kriegtein AR. Low-coverage single-cell mRNA sequencing reveals cellular heterogeneity and activated signaling pathways in developing cerebral cortex. Nature Biotechnology 32:1053 (2014).
• DeRosa BA; Belle KC; Thomas BJ; Cukier HN; Pericak-Vance MA; Vance JM; Dykxhoom DM. hVGAT-mCherry: A novel molecular tool for analysis of GABAergic neurons derived from human pluripotent stem cells. Mol Cell Neurosci 68:244 (2015).
• Pré D; Nestor MW; Sproul AA; Jacob S; Koppensteiner P; Chinchalongpom V; Zimmer M; Yamamoto A; Noggle SA; Arancio O. A time course analysis of the electrophysiological properties of neurons differentiated from human induced pluripotent stem cells (iPSCs). PLoS ONE 9(7): e103418 (2014).
• Zhang, Z; Wu, W-S. Sodium Butyrate Promotes Generation of Human Induced Pluripotent Stem Cells Through Induction of the miR302/367 Cluster. Stem Cells and Development. 22(16): 2268-2277 (2013).
• Blauwkamp TA; Nigam S; Ardehali R; Weissman IL; Nusse R. Endogenous Wnt signalling in human embryonic stem cells generates an equilibrium of distinct lineage-specified progenitors. Nature Communications 3:1070 (2012).
• 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. (2012) Robust cardiomyocyte differentiation from human pluripotent stem cells via temporal modulation of canonical Wnt signaling. Proc Natl Acad Sci USA 109: E1848 (2012).
• Nagy, K., Sung, H-K., Zhang, P., Laflamme, S., Vincent, P, Agha-Mohammadi, S., Woltjen, K., Monetti, C., Michael, I. P., Smith, L. C., Nagy, A. Induced Pluripotent Stem Cell Lines Derive from Equine Fibroblasts. Stem Cell Reviews and Reports 7:693 (2011).
• Wang, B., Miyagoe-Suzuki, Y., Yada, E., Ito, N., Nishiyama, T., Nakamura, M., Ono, Y., Motohashi, N., Segawa, M., Masuda, S., Takeda, S. Reprogramming Efficiency and Quality of Induced Pluripotent Stem Cells (iPSCs) Generated from Muscle-derived Fibroblasts of MDX Mice at Different Ages. PLOS Currents Muscular Dystrophy2011 Oct 27 . Edition 1. doi: 10.1371/currents.RRN1274 .
• Cho Y; Szabolcs A; Duuta SK; Yaqoob U; Jagavelu K; Leof EB; Urrutia RA; Shah VH; Mukhopadhyay D. Neuropilin-1 mediates divergent R-Smad signaling and the myofibroblast phenotype. J Biol Chem 285:31840 (2010).