MK-0752
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
MK-0752是一种在临床开发上非常有效的γ分泌酶抑制剂，IC50值约为50 nM。γ分泌酶是Notch切割机制的重要组成部分，它可以催化受体蛋白跨膜结构域的切割。
Notch信号需要γ分泌酶来切割Notch，释放Notch的胞内结构域（NICD）从而激活靶基因的转录。Notch信号在正常组织发育、细胞命运决定、增殖和存活中起着重要作用。通过结合同源配体Delta1、Delta2、Delta3、Jagged1和Jagged2，Notch信号被激活。在体外，抑制Notch信号可以抑制BC细胞的增值。
参考文献：
I. E. Krop, M. Kosh, I. Fearen, J. Savoie, A. Dallob, C. Matthews, J. Stone, E. Winer, S. J. Freedman and P. Lorusso. Phase I pharmacokinetic (PK), and pharmacodynamic (PD) trial of the novel oral Notch inhibitor MK-0752 in patients (pts) with advanced breast cancer (BC) and other solid tumors. J Clin Oncol (Meeting Abstracts) June 2006 vol. 24 no. 18_suppl 10574.
Maryam Fouladi, Clinton F. Stewart, James Olson, Lars M. Wagner, Arzu Onar-Thomas, Mehmet Kocak, Roger J. Packer, Stewart Goldman, Sridharan Gururangan, Amar Gajjar, Tim Demuth, Larry E. Kun, James M. Boyett and Richard J. Gilbertson. Phase I Trial of MK-0752 in Children With Refractory CNS Malignancies: A Pediatric Brain Tumor Consortium Study. JCO September 10, 2011 vol. 29 no. 26 3529-3534
- 1. Di Huang, Jiamin Qiu, et al. "In Vitro Evaluation of Clinical Candidates of γ-Secretase Inhibitors: Effects on Notch Inhibition and Promoting Beige Adipogenesis and Mitochondrial Biogenesis." Pharm Res 2020 Sep 4;37(10):185. PMID: 32888109
- 2. Chen X, Gong L, et al. "Sequential combination therapy of ovarian cancer with cisplatin and γ-secretase inhibitor MK-0752." Gynecol Oncol. 2016 Mar;140(3):537-44. PMID: 26704638
| Storage | Store at -20°C |
| M.Wt | 442.9 |
| Cas No. | 471905-41-6 |
| Formula | C21H21ClF2O4S |
| Synonyms | MK 0752, MK0752 |
| Solubility | ≥22.15 mg/mL in DMSO; insoluble in H2O; ≥48.8 mg/mL in EtOH with ultrasonic |
| Chemical Name | 3-[4-(4-chlorophenyl)sulfonyl-4-(2,5-difluorophenyl)cyclohexyl]propanoic acid |
| SDF | Download SDF |
| Canonical SMILES | C1CC(CCC1CCC(=O)O)(C2=C(C=CC(=C2)F)F)S(=O)(=O)C3=CC=C(C=C3)Cl |
| 运输条件 | 蓝冰运输或根据您的需求运输。 |
| 一般建议 | 不同厂家不同批次产品溶解度各有差异，仅做参考。若实验所需浓度过大至产品溶解极限，请添加助溶剂助溶或自行调整浓度。溶液形式一般不宜长期储存，请尽快用完。 |
| 细胞实验[1]： | |
|
细胞系 |
SH-SY5Y细胞 |
|
溶解方法 |
在DMSO中的溶解度>10 mM。为了获得更高的浓度，可以将离心管在37℃加热10分钟和/或在超声波浴中震荡一段时间。原液可以在-20℃以下储存几个月。 |
|
反应条件 |
IC50：5 nM |
|
应用 |
MK-0752是一种适度有效的γ分泌酶抑制剂。在人SH-SY5Y细胞中，MK-0752剂量依赖地抑制Aβ40的产生，IC50值为5 nM。 |
| 动物实验[1]： | |
|
动物模型 |
雄性CMP恒河猴 |
|
剂量 |
60 mg/kg和240 mg/kg；口服给药。 |
|
应用 |
MK-0752口服给药后剂量依赖地减少Aβ的水平。240 mg/kg的MK-0752处理48小时后，Aβ的水平仅恢复到基线水平的50%，而60 mg/kg治疗组在30小时之后Aβ的水平恢复到基线水平，而在治疗后的33-48小时，血浆Aβ水平出现反弹，高于基线水平。 |
|
注意事项 |
请测试所有化合物在室内的溶解度，实际溶解度和理论值可能略有不同。这是由实验系统的误差引起的，属于正常现象。 |
|
References: [1] Cook J J, Wildsmith K R, Gilberto D B, et al. Acute γ-secretase inhibition of nonhuman primate CNS shifts amyloid precursor protein (APP) metabolism from amyloid-β production to alternative APP fragments without amyloid-β rebound[J]. The Journal of Neuroscience, 2010, 30(19): 6743-6750. |
|
| Targets | γ-secretase | |||||
| IC50 | 5 nM |
质量控制和MSDS
- 批次:
化学结构
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