产品号 #72232_C
激活素/BMP/TGF-β 通路抑制剂；抑制 ALK4、ALK5 和 ALK7
总览
SB431542 是一种选择性强效 TGF-β/Activin/NODAL 通路抑制剂，通过竞争 ATP 结合位点抑制 ALK5（IC₅₀ = 94 nM）、ALK4（IC₅₀ = 140 nM）和 ALK7。它不抑制 BMP I 型受体 ALK2、ALK3 和 ALK6（Inman et al.; Laping et al.）。本产品以水合物形式提供。
重编程
·取代 SOX2，将小鼠成纤维细胞重编程为诱导多能干细胞 (iPS) （Ichida et al.）。
·与 PD0325901 和 Thiazovivin 联合使用，可提高将人体细胞重编程为 iPS 细胞的效率（Lin et al.）。
·与 CHIR99021、ISX-9、Forskolin 和 I-BET151 联合使用，可将成纤维细胞直接谱系重编程为成熟神经元（Li et al.）。
分化
·与 LDN193189 或 Noggin 联合使用，可促进人 PSC 向神经祖细胞分化（Chambers et al. 2009, Chambers et al. 2012）。
·促进小鼠胚胎干 (ES) 来源内皮细胞的增殖和片状结构形成（Watabe et al.）。
·增强小鼠和人 PSC 向心肌细胞的分化（Kattman et al.）。
·抑制人多能干细胞 (PSC) 的自我更新并促进其分化，表明 TGF-β/Activin/NODAL 通路在其维持中的重要性（James et al., Vallier et al.）。
细胞类型
心肌细胞，PSC衍生，内皮细胞，神经细胞，PSC衍生，神经干/祖细胞，神经元
种属
人，小鼠，非人灵长类，其它细胞系，大鼠
应用
分化，重编程
研究领域
神经科学，干细胞生物学
CAS 编号
Not applicable
化学式
C₂₂H₁₆N₄O₃ • XH₂O
纯度
≥98%
通路
Activin/Nodal/TGFβ
靶点
ALK
Protocols and Documentation
Find supporting information and directions for use in the Product Information Sheet or explore additional protocols below.
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.
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.
更多信息
| Species | Human, Mouse, Non-Human Primate, Other, Rat |
|---|---|
| Cas Number | Not applicable |
| Chemical Formula | C₂₂H₁₆N₄O₃ • XH₂O |
| Purity | ≥ 98% |
| Target | ALK |
| Pathway | Activin/Nodal/TGFβ |
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