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Necrostatin 2 racemate

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Chemical Structure| 852391-15-2 同义名 : Nec-1S;Necrostatin 1S;(±)-Necrostatin-2;Necrostatin-1 stable;7-Cl-O-Nec1
CAS号 : 852391-15-2
货号 : A466111
分子式 : C13H12ClN3O2
纯度 : 99%+
分子量 : 277.706
MDL号 : MFCD26743828
存储条件：

粉末 Sealed in dry,Room Temperature

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 50 mg/mL(180.05 mM)，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
描述 RIPK1 is a key regulator of innate immune signalling pathways. To ensure an optimal inflammatory response, RIPK1 is regulated post-translationally by well-characterized ubiquitylation and phosphorylation events, as well as by caspase-8-mediated cleavage[3].RIPK1 and RIPK3 (receptor-interacting serine/threonine protein kinases 1/3) interact by virtue of their RIP homotypic interaction motifs to mediate a form of cell death called necroptosis, although mice lacking these kinases have very different phenotypes. RIPK1-deficient mice die soon after birth, whereas RIPK3-deficient mice are healthy. Necroptosis involves cell rupture and is triggered by tumor necrosis factor (TNF), Toll-like receptors (TLRs), or the T cell receptor (TCR) when pro-apoptotic caspase-8 is inhibited[4]. In lesional psoriatic epidermis, RIPK1-expression was decreased compared with that in normal epidermis. Cytokines involved in the pathomechanism of psoriasis, such as IL-1β, IL-17A, IL-22 and TRAIL, reduced RIPK1-expression in normal human epidermal keratinocytes (HEK) in vitro. In addition, RIPK1-knockdown enhanced TRAIL-mediated expression of psoriasis-relating cytokines, such as IL-1β, IL-6, IL-8, TNF-α, in HEK[5].RIPK1 is upregulated in human colorectal cancer and promotes cell proliferation when overexpressed in a colon cancer cell line. RIPK1 interacts with mitochondrial Ca2+ uniporter (MCU) to promote proliferation by increasing mitochondrial Ca2+ uptake and energy metabolism. The ubiquitination site of RIPK1 (RIPK1-K377) was critical for this interaction with MCU and function in promoting cell proliferation[6].Necrostatin 2 racemate is an potent and specific inhibitor of RIPK1[7].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

3.60mL

0.72mL

0.36mL

18.00mL

3.60mL

1.80mL

36.01mL

7.20mL

3.60mL
参考文献

[1]Teng X, Keys H, et al. Structure-activity relationship study of [1,2,3] thiadiazole necroptosis inhibitors. Bioorg Med Chem Lett. 2007 Dec 15;17(24):6836-40. Epub 2007 Oct 17.

[2]Teng X, Degterev A, et al. Structure-activity relationship study of novel necroptosis inhibitors. Bioorg Med Chem Lett. 2005 Nov 15;15(22):5039-44.

[3]Najoua Lalaoui,et al. Mutations that prevent caspase cleavage of RIPK1 cause autoinflammatory disease. Nature. 2020 Jan;577(7788):103-108.

[4]Kim Newton. RIPK1 and RIPK3: critical regulators of inflammation and cell death. Trends Cell Biol. 2015 Jun;25(6):347-53.

[5]Nao Saito,et al. RIPK1 downregulation in keratinocyte enhances TRAIL signaling in psoriasis. J Dermatol Sci. 2018 Jul;91(1):79-86.

[6]Fanxin Zeng,et al. RIPK1 Binds MCU to Mediate Induction of Mitochondrial Ca 2+ Uptake and Promotes Colorectal Oncogenesis. Cancer Res. 2018 Jun 1;78(11):2876-2885.

[7] Takahashi N , Duprez L , Grootjans S , et al. Necrostatin-1 analogues: critical issues on the specificity, activity and in vivo use in experimental disease models[J]. Cell Death and Disease, 2012, 3(11):e437.