| BIX 02189Selective MEK5 inhibitor |
Sample solution is provided at 25 µL, 10mM.
Nature.2017 Jan 19;541(7637):417-420.
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- Purity = 99.13%
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Chemical structure
| Description | BIX02189 is a selective inhibitor of MEK5 with an IC50 value of 1.5 nM. | |||||
| Targets | MEK5 | ERK5 | TGFβR1 | |||
| IC50 | 1.5 nM | 59 nM | 580 nM | |||
| Cell experiment[1]: | |
Cell lines | HeLa cells |
Preparation method | The solubility of this compound in DMSO is > 22.1mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
Reacting condition | 1.5 h, 10 µM |
Applications | BIX02189 inhibited MEK5 and ERK5 catalytic activity with IC50 values of 1.5 nM and 59 nM, respectively. BIX02189 inhibited ERK5 phosphorylation activated by sorbitol in a dose-dependent manner in HeLa cells. BIX02189 also inhibited luciferase gene expression induced by MEF2 in a dose dependent manner in HeLa and 293T cells. |
| Animal experiment [2]: | |
Animal models | Specific pathogen-free C57BL/6 mice |
Dosage form | Intraperitoneal injection, 10 mg/kg |
Application | BIX02189 significantly inhibited collagen accumulation and fibrogenic histological changes in the lung tissues of bleomycin-treated mice. BIX02189 also improved survival rate of mice after bleomycin inoculation. |
Other notes | Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
References: [1]. Tatake R J, O’Neill M M, Kennedy C A, et al. Identification of pharmacological inhibitors of the MEK5/ERK5 pathway[J]. Biochemical and biophysical research communications, 2008, 377(1): 120-125. [2]. Kim S, Lim J H, Woo C H. ERK5 inhibition ameliorates pulmonary fibrosis via regulating Smad3 acetylation[J]. The American journal of pathology, 2013, 183(6): 1758-1768. | |
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| Cas No. | 1094614-85-3 | SDF | Download SDF |
| Chemical Name | (3Z)-3-[[3-[(dimethylamino)methyl]anilino]-phenylmethylidene]-N,N-dimethyl-2-oxo-1H-indole-6-carboxamide | ||
| Canonical SMILES | CN(C)CC1=CC(=CC=C1)NC(=C2C3=C(C=C(C=C3)C(=O)N(C)C)NC2=O)C4=CC=CC=C4 | ||
| Formula | C27H28N4O2 | M.Wt | 440.54 |
| Solubility | ≥22.05mg/mL in DMSO | Storage | Store at -20°C |
| Physical Appearance | A solid | Shipping Condition | Evaluation sample solution : ship with blue ice.All other available size:ship with RT , or blue ice upon request |
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. | ||
BIX 02189 is a selective inhibitor of MEK5 with IC50 value of 1.5 nM 1.
BIX 02189 belongs to the indolinone kinase inhibitor series. It selectively inhibited the catalytic activity of MEK5 but not other closely related kinases such as MEK1, MEK2, ERK2 and JNK2. BIX 02189 also inhibited ERK5 with IC50 value of 59 nM. In HeLa cells, treatment of BIX 02189 inhibited the phosphorylation of ERK5 but not ERK1/2. Besides that, BIX 02189 prevented the transcription of the downstream substrate MEF2C in HeLa and HEK293 cells. Moreover, in a three-dimensional lymphangiogenic sprouting assay, BIX 02189 resulted in an inhibition of lymphangiogenic sprouting with a minimal effective concentration of 1 μM 1,2.
References:1.Tatake R J, O’Neill M M, Kennedy C A, et al. Identification of pharmacological inhibitors of the MEK5/ERK5 pathway. Biochemical and biophysical research communications, 2008, 377(1): 120-125.2.Schulz M M P, Reisen F, Zgraggen S, et al. Phenotype-based high-content chemical library screening identifies statins as inhibitors of in vivo lymphangiogenesis. Proceedings of the National Academy of Sciences, 2012, 109(40): E2665-E2674.
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DNA连接酶作用于基因工程，用于连接两个DNA片段间的磷酸二酯键。
可分为以下几个类群:(1)依赖DNA的DNA聚合酶；(2)依赖RNA的DNA聚合酶；(3)依赖DNA的RNA聚合酶；(4)依赖RNA的RNA聚合酶。前两者是DNA聚合酶，它使DNA复制链按模板顺序延长。如在原核生物中仅就大肠杆菌中已被发现的就有三种(分别简称为PolⅠ，PolⅡ和PolⅢ等)；DNA聚合酶只能在有引物的基础上，即在DNA或RNA引物的3′-OH延伸，这DNA的合成方向记为5′→3′。换言之DNA聚合酶催化反应除底物(αNTP)外，还需要Mg2+ 、模板DNA和引物，迄今细胞内尚无发现可从单体起始DNA的合成。同样，上述(3)和(4)是催化RNA生物合成反应中最主要的RNA合成酶，它们以四种三磷酸核糖核苷(NTP)为底物，并需有DNA模板以及Mn2 及Mg2 的存在下，在前一个核苷酸3′-OH与下一个核苷酸的5′-P聚合形成3′，5′-磷酸二酯键，其新生链的方向也是5′→3′。RNA聚合酶也大量存在于原核和真核生物的细胞中。如大肠杆菌RNA聚合酶分子量4.8×105，由5条多肽链组成，分别命名为α，α，β，β′，和γ，全酶可用α2ββ′λ表示。真核生物RNA聚合酶分子大于5×105，由10～12个大小不等亚基组成。聚合酶除作为自然界生命活动中不可缺少的组分外，在实验室中大多用作生命科学研究的工具酶类之一。向左转|向右转
再来说真核生物,真核生物的DNA聚合酶分为α,β,γ,δ,ε,.首先我来说三个和原核生物中的Ⅰ,Ⅱ,Ⅲ功能相同的酶.ε类似于原核生物DNA聚合酶Ⅰ,β类似于原核生物DNA聚合酶Ⅱ,δ类似于原核生物DNA聚合酶Ⅲ.α具有引物酶活性,而γ则是作为复制真核生物线粒体内的DNA所需要的酶.
解旋酶：在DNA复制、转录时，作用于DNA双链，将双链DNA解开形成单链。
RNA聚合酶：在转录过程中，作用于游离的核糖核苷酸，将它们连接形成mRNA链
下面是六种不同耐热聚合酶的比较：
Taq：扩增效率最高的耐热DNA聚合酶，能很好的扩增6kb以下的DNA片段。扩增碱基出错率为10-5左右。
Pfu：目前保真度最高的耐热DNA聚合酶，碱基出错率为10-6，但扩增效率低于Taq酶，一般能很好的扩增2kb以下的片段。
TaqPlus：集扩增效率高和保真度好于一身。扩增效率比Pfu高，保真度比Taq好。能有效的扩增10kb以下的片段。
HotstartTaq：经过化学修饰的耐热DNA聚合酶。此酶在常温下，活性被化学基团封闭，要在94℃-95℃加热数分钟才能回复正常活力开始反应，避免了起始循环较低温度下的非特异性扩增，提高了反应的灵敏度和特异性。
LongTaq：具有3’-5’外切酶活性的耐热DNA聚合酶，它不但扩增效率高而且错配率低，对于简单模板可扩增长达40kb的模板，对复杂模板也可扩增长达15kb的片段。
TaqPlatinum：热启动高保真耐热DNA聚合酶。如果对保真度要求很高，而用Pfu扩增有难度，可选用TaqPlatinum，一般扩增长度可达4kb。
根据不同的实验目的选择最合适的酶，
克隆普通长度的目的DNA片段：Taq、TaqPlus
保真度要求较高，片段比较短，如点突变、基因筛选等：Pfu、TaqPlatinum
高保真长片段扩增，如构建基因图谱及分子遗传学研究等：LongTaq、TaqPlus
扩增基因组模板，需要降低背景：HotstartTaq、TaqPlatinum
扩增GC含量较高或二级结构较复杂的模板：TaqPlus、LongTaq、TaqPlatinum
实时荧光定量PCR反应：Taq、HotstartTaq、TaqPlatinum
从菌株或质粒模板，筛选鉴定目的克隆，扩增6kb以下的片段：Taq、TaqPlus、2×TaqPCRMasterMix
模板比较复杂或目的片段丰度低，用普通Taq酶扩增不出条带：2×TaqPCRMasterMix、2×PfuPCRMasterMix
聚合酶就是多功能的dna的制作机器
DNA聚合酶和DNA连接酶作用的位点都是3'5'磷酸二酯键；但DNA连接酶是作用在游离的DNA片段间，使其连接成为一条完整的DNA链，而DNA聚合酶则是将游离的脱氧核糖核苷酸连接成DNA片段。
