SB431542 (Hydrate)
Activin/BMP/TGF-β pathway inhibitor; Inhibits ALK4, ALK5, and ALK7
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Overview
SB431542 is a selective and potent inhibitor of the TGF-β/Activin/NODAL pathway that inhibits ALK5 (IC₅₀ = 94 nM), ALK4 (IC₅₀ = 140 nM), and ALK7 by competing for the ATP binding site. It does not inhibit the BMP type I receptors ALK2, ALK3, and ALK6 (Inman et al.; Laping et al.). This product is supplied as the hydrate form of the molecule.
REPROGRAMMING
· Replaces SOX2 in the reprogramming of mouse fibroblasts to induced pluripotent stem (iPS) cells (Ichida et al.).
· Increases the efficiency of reprogramming human somatic cells to iPS cells, in combination with PD0325901 and Thiazovivin (Lin et al.).
· Direct lineage reprogramming of fibroblasts to mature neurons, in combination with CHIR99021, ISX-9, Forskolin, and I-BET151 (Li et al.).
DIFFERENTIATION
· Promotes differentiation of neural progenitor cells from human PSCs, in combination with either LDN193189 or Noggin (Chambers et al. 2009, Chambers et al. 2012).
· Promotes proliferation and sheet formation of mouse embryonic stem (ES)-derived endothelial cells (Watabe et al.).
· Enhances differentiation of cardiomyocytes from mouse and human PSCs (Kattman et al.).
· Inhibits the self-renewal and causes differentiation of human pluripotent stem cells (PSCs), demonstrating the importance of the TGF-β/Activin/NODAL pathway in their maintenance (James et al., Vallier et al.).
REPROGRAMMING
· Replaces SOX2 in the reprogramming of mouse fibroblasts to induced pluripotent stem (iPS) cells (Ichida et al.).
· Increases the efficiency of reprogramming human somatic cells to iPS cells, in combination with PD0325901 and Thiazovivin (Lin et al.).
· Direct lineage reprogramming of fibroblasts to mature neurons, in combination with CHIR99021, ISX-9, Forskolin, and I-BET151 (Li et al.).
DIFFERENTIATION
· Promotes differentiation of neural progenitor cells from human PSCs, in combination with either LDN193189 or Noggin (Chambers et al. 2009, Chambers et al. 2012).
· Promotes proliferation and sheet formation of mouse embryonic stem (ES)-derived endothelial cells (Watabe et al.).
· Enhances differentiation of cardiomyocytes from mouse and human PSCs (Kattman et al.).
· Inhibits the self-renewal and causes differentiation of human pluripotent stem cells (PSCs), demonstrating the importance of the TGF-β/Activin/NODAL pathway in their maintenance (James et al., Vallier et al.).
Alternative Names
SB-431542
Cell Type
Cardiomyocytes, PSC-Derived, Endothelial Cells, Neural Cells, PSC-Derived, Neural Stem and Progenitor Cells, Neurons
Species
Human, Mouse, Rat, Non-Human Primate, Other
Application
Differentiation, Reprogramming
Area of Interest
Neuroscience, Stem Cell Biology
CAS Number
Not applicable
Chemical Formula
C₂₂H₁₆N₄O₃ • XH₂O
Molecular Weight
384.4 g/mol
Purity
≥ 98%
Pathway
Activin/Nodal/TGFβ
Target
ALK
Protocols and Documentation
Find supporting information and directions for use in the Product Information Sheet or explore additional protocols below.
Document Type
Product Name
Catalog #
Lot #
Language
Document Type
Product Information Sheet 1
Product Name
SB431542 (Hydrate)
Catalog #
72232, 72234 Lot #
All other lots Language
English Document Type
Product Information Sheet 2
Product Name
SB431542 (Hydrate)
Catalog #
72232, 72234 Lot #
Lot 1000012400 and higher Language
English Document Type
Product Information Sheet 3
Product Name
SB431542 (Hydrate)
Catalog #
72232, 72234, 100-1051 Lot #
All Language
English Document Type
Safety Data Sheet
Product Name
SB431542 (Hydrate)
Catalog #
72232, 72234 Lot #
All Language
English Document Type
Safety Data Sheet
Product Name
SB431542 (Hydrate)
Catalog #
100-1051 Lot #
All Language
English Applications
This product is designed for use in the following research area(s) as part of the highlighted workflow stage(s). Explore these workflows to learn more about the other products we offer to support each research area.
Research Area
Workflow Stages
Workflow Stages for
Human Pluripotent Stem Cell Research
Workflow Stages for
hPSC-Derived Neural Cell Research
Workflow Stages for
hPSC-Derived Mesoderm Cell Research
Workflow Stages for
Mouse Pluripotent Stem Cell Research
Resources and Publications
Educational Materials (5)
Publications (11)
Small-Molecule-Driven Direct Reprogramming of Mouse Fibroblasts into Functional Neurons.
Cell stem cell 2015 AUG
Abstract
Recently, direct reprogramming between divergent lineages has been achieved by the introduction of regulatory transcription factors. This approach may provide alternative cell resources for drug discovery and regenerative medicine, but applications could be limited by the genetic manipulation involved. Here, we show that mouse fibroblasts can be directly converted into neuronal cells using only a cocktail of small molecules, with a yield of up to textgreater90% being TUJ1-positive after 16 days of induction. After a further maturation stage, these chemically induced neurons (CiNs) possessed neuron-specific expression patterns, generated action potentials, and formed functional synapses. Mechanistically, we found that a BET family bromodomain inhibitor, I-BET151, disrupted the fibroblast-specific program, while the neurogenesis inducer ISX9 was necessary to activate neuron-specific genes. Overall, our findings provide a proof of principle" for chemically induced direct reprogramming of somatic cell fates across germ layers without genetic manipulation�
Combined small-molecule inhibition accelerates developmental timing and converts human pluripotent stem cells into nociceptors.
Nature biotechnology 2012 JUL
Abstract
Considerable progress has been made in identifying signaling pathways that direct the differentiation of human pluripotent stem cells (hPSCs) into specialized cell types, including neurons. However, differentiation of hPSCs with extrinsic factors is a slow, step-wise process, mimicking the protracted timing of human development. Using a small-molecule screen, we identified a combination of five small-molecule pathway inhibitors that yield hPSC-derived neurons at textgreater75% efficiency within 10 d of differentiation. The resulting neurons express canonical markers and functional properties of human nociceptors, including tetrodotoxin (TTX)-resistant, SCN10A-dependent sodium currents and response to nociceptive stimuli such as ATP and capsaicin. Neuronal fate acquisition occurs about threefold faster than during in vivo development, suggesting that use of small-molecule pathway inhibitors could become a general strategy for accelerating developmental timing in vitro. The quick and high-efficiency derivation of nociceptors offers unprecedented access to this medically relevant cell type for studies of human pain.
Stage-specific optimization of activin/nodal and BMP signaling promotes cardiac differentiation of mouse and human pluripotent stem cell lines.
Cell stem cell 2011 FEB
Abstract
Efficient differentiation of embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) to a variety of lineages requires step-wise approaches replicating the key commitment stages found during embryonic development. Here we show that expression of PdgfR-α segregates mouse ESC-derived Flk-1 mesoderm into Flk-1(+)PdgfR-α(+) cardiac and Flk-1(+)PdgfR-α(-) hematopoietic subpopulations. By monitoring Flk-1 and PdgfR-α expression, we found that specification of cardiac mesoderm and cardiomyocytes is determined by remarkably small changes in levels of Activin/Nodal and BMP signaling. Translation to human ESCs and iPSCs revealed that the emergence of cardiac mesoderm could also be monitored by coexpression of KDR and PDGFR-α and that this process was similarly dependent on optimal levels of Activin/Nodal and BMP signaling. Importantly, we found that individual mouse and human pluripotent stem cell lines require optimization of these signaling pathways for efficient cardiac differentiation, illustrating a principle that may well apply in other contexts.
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Quality Statement:
PRODUCTS ARE FOR RESEARCH USE ONLY AND NOT INTENDED FOR HUMAN OR ANIMAL DIAGNOSTIC OR THERAPEUTIC USES UNLESS OTHERWISE STATED. FOR ADDITIONAL INFORMATION ON QUALITY AT STEMCELL, REFER TO WWW.STEMCELL.COM/COMPLIANCE.
