产品号 #72642_C
JNK通路抑制剂；抑制JNK1， JNK2和JNK3
总览
SP600125是高效且可逆的JNK1-3抑制剂（IC50 = 0.11 μM）（Bennett et al.）。其具有细胞通透性和剂量依赖性，可抑制细胞中c-JUN的磷酸化，阻断单核细胞中COX-2和TNF-α的表达，阻断T细胞中IL-10、TNF-α和IFN-的表达（Bennett et al.）。
重编程
·与CHIR99021、RepSox、Forskolin、Gö6983、丙戊酸和Y-27632结合使用，可将成纤维细胞直接重编程为成熟神经元（Hu et al.）。
分化
·抑制BMP9诱导的成骨分化。用于培养小鼠间充质干细胞（MSCs）和原代骨髓基质细胞（Zhao et al.）。
·促进脂肪生成分化，但抑制人间充质干细胞的成骨分化（Bilkovski et al.; Liu et al.; Qiu et al.; Tominaga et al.）。
·在神经元培养的早期阶段添加时，会导致细胞死亡并抑制神经发生（Tiwari et al.）。
细胞类型
脂肪细胞，间充质干/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
129-56-6
化学式
C₁₄H₈N₂O
纯度
≥98%
通路
JNK
靶点
JNK1，JNK2，JNK3
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 (2)
Publications (8)
Direct Conversion of Normal and Alzheimer's Disease Human Fibroblasts into Neuronal Cells by Small Molecules. Cell stem cell 2015 AUG
Abstract
Neuronal conversion from human fibroblasts can be induced by lineage-specific transcription factors; however, the introduction of ectopic genes limits the therapeutic applications of such induced neurons (iNs). Here, we report that human fibroblasts can be directly converted into neuronal cells by a chemical cocktail of seven small molecules, bypassing a neural progenitor stage. These human chemical-induced neuronal cells (hciNs) resembled hiPSC-derived neurons and human iNs (hiNs) with respect to morphology, gene expression profiles, and electrophysiological properties. This approach was further applied to generate hciNs from familial Alzheimer's disease patients. Taken together, our transgene-free and chemical-only approach for direct reprogramming of human fibroblasts into neurons provides an alternative strategy for modeling neurological diseases and for regenerative medicine.
Activation of JNKs is essential for BMP9-induced osteogenic differentiation of mesenchymal stem cells. BMB reports 2013 AUG
Abstract
Although BMP9 is highly capable of promoting osteogenic differentiation of mesenchymal stem cell (MSCs), the molecular mechanism involved remains to be fully elucidated. Here, we explore the possible involvement and detail role of JNKs (c-Jun N-terminal kinases) in BMP9-induced osteogenic differentiation of MSCs. It was found that BMP9 stimulated the activation of JNKs in MSCs. BMP9-induced osteogenic differentiation of MSCs was dramatically inhibited by JNKs inhibitor SP600125. Moreover, BMP9-activated Smads signaling was decreased by SP600125 treatment in MSCs. The effects of inhibitor are reproduced with adenoviruses expressing siRNA targeted JNKs. Taken together, our results revealed that JNKs was activated in BMP9-induced osteogenic differentiation of MSCs. What is most noteworthy, however, is that inhibition of JNKs activity resulted in reduction of BMP9-induced osteogenic differentiation of MSCs, implying that activation of JNKs is essential for BMP9 osteoinductive activity.
A chromatin-modifying function of JNK during stem cell differentiation. Nature genetics 2012 JAN
Abstract
Signaling mediates cellular responses to extracellular stimuli. The c-Jun NH(2)-terminal kinase (JNK) pathway exemplifies one subgroup of the mitogen-activated protein (MAP) kinases, which, besides having established functions in stress response, also contribute to development by an unknown mechanism. We show by genome-wide location analysis that JNK binds to a large set of active promoters during the differentiation of stem cells into neurons. JNK-bound promoters are enriched with binding motifs for the transcription factor NF-Y but not for AP-1. NF-Y occupies these predicted sites, and overexpression of dominant-negative NF-YA reduces the JNK presence on chromatin. We find that histone H3 Ser10 (H3S10) is a substrate for JNK, and JNK-bound promoters are enriched for H3S10 phosphorylation. Inhibition of JNK signaling in post-mitotic neurons reduces phosphorylation at H3S10 and the expression of target genes. These results establish MAP kinase binding and function on chromatin at a novel class of target genes during stem cell differentiation.
更多信息
| Species | Human, Mouse, Non-Human Primate, Other, Rat |
|---|---|
| Cas Number | 129-56-6 |
| Chemical Formula | C₁₄H₈N₂O |
| Purity | ≥ 98% |
| Target | JNK1, JNK2, JNK3 |
| Pathway | JNK |
相关产品
-
CHIR99021WNT 通路激活剂；抑制 GSK3
-
ForskolincAMP 通路激活剂；激活腺苷酸环化酶
-
RepSox（盐酸盐）激活素/BMP/TGF-β通路抑制剂；抑制ALK5
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.
