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RIPA-56

RIP 激酶抑制剂
规格或纯度: 98%
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货号 (SKU) 包装规格 是否现货 价格 数量
R413493-5mg
5mg 现货 Stock Image
R413493-10mg
10mg 现货 Stock Image
R413493-25mg
25mg 现货 Stock Image
R413493-50mg
50mg 现货 Stock Image
R413493-100mg
100mg 现货 Stock Image
R413493-200mg
200mg 现货 Stock Image

基本描述

规格或纯度 98%
英文名称 RIPA-56
别名 N-苄基-N-羟基-2,2-二甲基丁酰胺, RIPA56
生化机理 RIPA-56 is a highly-potent, selective, and metabolically stable RIP1 (RIPK1) inhibitor.RIPA-56是一种代谢稳定的III型激酶抑制剂,通过将RIP1锁定在非活性形式,以高效和选择性的方式(RIP1 IC50=13 nM)靶向受体相互作用蛋白1激酶(RIP1;RIPK1),没有抑制作用对RIP3,IDO或一组多种激酶(分别在10、200和5 μM下测试)的效力。RIPA-56可防止培养物中凋亡/NF-κB途径阻断(EC50=27 nM/鼠L929和28 nM/人HT-29细胞)引起的TNFα诱导的坏死病(坏死),以及TNFα诱导的死亡率和多器官体内全身性炎症反应综合征(SIRS)小鼠模型中的损伤(3 mg/kg/12 h或单次6 mg/kg ip的100%存活率),具有良好的药代动力学和生物利用度(10 mg/kg po后)或ip剂量分别为2 mg/kg iv的22%和100%)。据报道,长期每日补充RIPA-56(在食物中为150或300 mg/kg)可防止小鼠衰老相关的雄性生殖系统退化。
储存温度 -20°C储存
运输条件 超低温冰袋运输
产品介绍

RIPA-56是一种高效力、代谢稳定的选择性RIP1 (RIPK1)抑制剂。


应用:

RIPA-56 是一种高效选择和代谢稳定的受体相互作用蛋白 1 (RIP1) 抑制剂,IC50 为 13 nM。RIPA-56 可用于研究全身炎症反应综合征。

Information

RIPA-56 RIPA-56 is a highly-potent, selective, and metabolically stable RIP1 (RIPK1) inhibitor.


Targets

RIP1 (Cell-free) 13 nM


In vitro

RIPA-56 shows efficient inhibition of RIP1 kinase activity, with an IC50 of 13 nM. It showed no inhibition of RIP3 kinase activity at a 10 μM concentration. RIPA-56 does not inhibit IDO activity at a concentration of 200 μM, which represents an estimated 10,000-fold selectivity window based on the RIP1 ADP-Glo activity of 13 nM.


In vivo

RIPA-56 has an impressive PK profile in mice, with a 3.1 h half-life, 22% oral bioavailability (PO), and 100% bioavailability from intraperitoneal injection (IP). RIPA-56 has great ability in transporting across blood brain barrier. In the SIRS mice disease model, RIPA-56 efficiently reduced tumor necrosis factor alpha (TNFα)-induced mortality and multi-organ damage.

名称和标识符

IUPAC Name N-benzyl-N-hydroxy-2,2-dimethylbutanamide
INCHI InChI=1S/C13H19NO2/c1-4-13(2,3)12(15)14(16)10-11-8-6-5-7-9-11/h5-9,16H,4,10H2,1-3H3
InChi Key AVYVHIKSFXVDBG-UHFFFAOYSA-N
Canonical SMILES CCC(C)(C)C(=O)N(CC1=CC=CC=C1)O
PubChem CID 121439991
分子量 221.3

化学和物理性质

溶解性 Solubility (25°C) In vitro DMSO: 44 mg/mL (198.82 mM); Ethanol: 44 mg/mL (198.82 mM); Water: Insoluble;

安全和危险性(GHS)

RIDADR NONHforallmodesoftransport

关联配体

Ligand ID 9643
名称 RIPA-56
别名 compound 56 [PMID: 27992216]
类别 Synthetic organic
学名 N-benzyl-N-hydroxy-2,2-dimethylbutanamide
生物活性评价 RIPA-56 is active against human and mouse RIPK1 and is efficacious in animal models . It is devoid of off-target IDO inhibiting activity.
评价 RIPA-56 is a highly potent, selective, and metabolically stable type III (allosteric) inhibitor of receptor-interacting protein kinase 1 (RIPK1) . It is claimed as compound 92 in patent WO2016101885 . RIPA-56 is a drug candidate for the treatment of systemic inflammatory response syndrome (SIRS).

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参考文献

1. Ren Y, Su Y, Sun L, He S, Meng L, Liao D, Liu X, Ma Y, Liu C, Li S et al..  (2017)  Discovery of a Highly Potent, Selective, and Metabolically Stable Inhibitor of Receptor-Interacting Protein 1 (RIP1) for the Treatment of Systemic Inflammatory Response Syndrome..  J Med Chem,  60  (3):  (972-986).  [PMID:27992216]

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品牌简介

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