产品号 #72172_C
MEK/ERK 通路抑制剂；抑制 MEK1 和 MEK2
总览
PD98059 是一种选择性、可穿透细胞的 MEK/ERK 通路抑制剂，其作用机制为阻止上游激酶激活 MEK1（IC₅₀ = 2 - 7 µM）和 MEK2（IC₅₀ = 50 µM）。它不抑制激活的 MEK 或 p38 MAPK 通路。（Alessi et al., Davies et al., Dudley et al.）
维护和自我更新
·增强小鼠胚胎干细胞 (ES) 的生长和自我更新（Burdon et al., Qi et al.）。
·允许从难以处理的 CBA 小鼠品系中分离小鼠 ES 细胞（Buehr and Smith）。
分化
·抑制小鼠 ES 细胞分化（Burdon et al.）。
·增强人间充质干细胞的脂肪形成分化并阻止其成骨分化 （Jaiswal et al.）。
癌症研究
·减少 AML 母细胞集落的数量，对正常造血祖细胞的影响极小（Milella et al.）。
别名
Not applicable
细胞类型
脂肪细胞，癌细胞及细胞系，白血病/淋巴瘤细胞，间充质干/祖细胞，多能干细胞
种属
人，小鼠，非人灵长类，其它细胞系，大鼠
应用
分化，扩增，培养
研究领域
癌症，干细胞生物学
CAS 编号
167869-21-8
化学式
C₁₆H₁₃NO₃
分子量
267.3 克/摩尔
纯度
≥98%
通路
MEK/ERK
靶点
MEK
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 (3)
Publications (8)
BMP4 supports self-renewal of embryonic stem cells by inhibiting mitogen-activated protein kinase pathways. Proceedings of the National Academy of Sciences of the United States of America 2004 APR
Abstract
The fate of pluripotent stem cells is tightly controlled during early embryonic development. Both the derivation and the maintenance of embryonic stem cells (ES cells) in vitro depend on feeder cell-derived growth factors that are largely unidentified. To dissect the mechanisms governing pluripotency, we conducted a screen to identify factors that are produced by mouse embryonic fibroblast STO cells and are required to maintain the pluripotency of ES cells. One of the factors is bone morphogenetic protein 4 (BMP4). Unexpectedly, the major effect of BMP4 on the self-renewal of ES cells is accomplished by means of the inhibition of both extracellular receptor kinase (ERK) and p38 mitogen-activated protein kinase (MAPK) pathways, and inhibitors of ERK and p38 MAPKs mimic the effect of BMP4 on ES cells. Importantly, inhibition of the p38 MAPK pathway by SB203580 overcomes the block in deriving ES cells from blastocysts lacking a functional Alk3, the BMP type IA receptor. These results uncover a paradigm for BMP signaling in the biology of pluripotent stem cells.
Genesis of embryonic stem cells. Philosophical transactions of the Royal Society of London. Series B, Biological sciences 2003 AUG
Abstract
Embryonic stem (ES) cells are permanent pluripotent stem cell lines established from pre-implantation mouse embryos. There is currently great interest in the potential therapeutic applications of analogous cells derived from human embryos. The isolation of ES cells is commonly presented as a straightforward transfer of cells in the early embryo into culture. In reality, however, continuous expansion of pluripotent cells does not occur in vivo, and in vitro is the exception rather than the norm. Both genetic and epigenetic factors influence the ability to derive ES cells. We have tracked the expression of a key marker and determinant of pluripotency, the transcription factor Oct-4, in primary cultures of mouse epiblasts and used this to assay the effect of experimental manipulations on the maintenance of a pluripotent cell compartment. We find that expression of Oct-4 is often lost prior to overt cytodifferentiation of the epiblast. The rate and extent of Oct-4 extinction varies with genetic background. We report that treatment with the MAP kinase/ERK kinase inhibitor PD98059, which suppresses activation of the mitogen-activated protein kinases Erk1 and Erk2, results in increased persistence of Oct-4-expressing cells. Oct-4 expression is also relatively sustained in cultures of diapause embryos and of isolated inner cell masses. Combination of all three conditions allowed the derivation of germline-competent ES cells from the normally refractory CBA mouse strain. These findings suggest that the genesis of an ES cell is a relatively complex process requiring epigenetic modulation of key gene expression over a brief time-window. Procedures that extend this time-window and/or directly regulate the critical genes should increase the efficiency of ES cell derivation.
Therapeutic targeting of the MEK/MAPK signal transduction module in acute myeloid leukemia. The Journal of clinical investigation 2001 SEP
Abstract
The mitogen-activated protein kinase (MAPK) pathway regulates growth and survival of many cell types, and its constitutive activation has been implicated in the pathogenesis of a variety of malignancies. In this study we demonstrate that small-molecule MEK inhibitors (PD98059 and PD184352) profoundly impair cell growth and survival of acute myeloid leukemia (AML) cell lines and primary samples with constitutive MAPK activation. These agents abrogate the clonogenicity of leukemic cells but have minimal effects on normal hematopoietic progenitors. MEK blockade also results in sensitization to spontaneous and drug-induced apoptosis. At a molecular level, these effects correlate with modulation of the expression of cyclin-dependent kinase inhibitors (p27(Kip1) and p21(Waf1/CIP1)) and antiapoptotic proteins of the inhibitor of apoptosis proteins (IAP) and Bcl-2 families. Interruption of constitutive MEK/MAPK signaling therefore represents a promising therapeutic strategy in AML.
更多信息
| Molecular Weight | 267.3 g/mol |
|---|---|
| Species | Human, Mouse, Non-Human Primate, Other, Rat |
| Alternative Names | Not applicable |
| Cas Number | 167869-21-8 |
| Chemical Formula | C₁₆H₁₃NO₃ |
| Purity | ≥ 98% |
| Target | MEK |
| Pathway | MEK/ERK |
PRODUCTS ARE FOR RESEARCH USE ONLY AND NOT INTENDED FOR HUMAN OR ANIMAL DIAGNOSTIC OR THERAPEUTIC USES UNLESS OTHERWISE STATED.
