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CAS No.: 1690172-25-8

I-191 Catalog No. CSN24477

Synonyms: MDK-2258

I-191 inhibited PAR2 binding of and activation by structurally distinct PAR2 agonists (trypsin, peptide, nonpeptide) at nanomolar concentrations.

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400-920-2911

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靶点选择性

生物活性

实验方案

技术信息

生物活性

描述GPCRs play pivotal roles in cellular sensing and intracellular responses to extracellular ligands. Protease-activated receptor 2 (PAR2) is a cell surface protein linked to G-protein dependent and independent intracellular signaling pathways that produce a wide range of physiological responses, including those related to metabolism, inflammation, pain, and cancer. PAR2 signaling pathways are involved in circulatory, cardiovascular, central nervous, gastrointestinal, metabolic, and respiratory systems. I-191 potently attenuated multiple PAR2-mediated intracellular signaling pathways leading to Ca²⁺ release, extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation, Ras homologue gene family, member A (RhoA) activation, and inhibition of forskolin-induced cAMP accumulation. I-191 also potently inhibited PAR2-mediated downstream functional responses, including expression and secretion of inflammatory cytokines and cell apoptosis and migration, in human colon adenocarcinoma grade II cell line (HT29) and human breast adenocarcinoma cells (MDA-MB-231). In a cell study, I-191 inhibited intracellular Ca²⁺ release induced by either 2f-LIGRL-NH2 (pIC₅₀ 7.2 ± 0.1) or bovine trypsin (pIC₅₀ 6.7 ± 0.1) in HT29 cells and I-191 did not induce any agonist-induced calcium response at concentrations up to 100 μM. HT29 cells were treated with I-191 from 1 µM to 10 µM for 48h, the result showed that I-191 could inhibit PAR2-activated migration of HT29 cells, a property which can be associated with inhibition of PAR2-mediated signaling through ERK1/2 phosphorylation. The inhibitory effects of I-191 on PAR2-induced migration of MDA-MB-231 breast cancer cells are consistent with observations for HT29 colon cancer cells, indicating potent antagonist properties in different cancer cell lines. Unlike the biased ligand GB88, which does not inhibit ERK1/2 activation or PAR2-induced migration, I-191 strongly inhibited 2f-LIGRL-NH2–induced migration of MDA-MB-231 cells^[1].
作用机制I-191 acts in a concentration-dependent manner to displace a PAR2 ligand, 2f-LIGRLO-NH2, for binding to PAR2. I-191 had a surprisingly short residence time on PAR2 but was still able to attenuate calcium release induced by either a proteolytic (trypsin) or peptidic (2f-LIGRL-NH2) agonist of PAR2^[1].
参考文献

[1] Nicholson A, Mahon J, Boland A, Beale S, Dwan K, Fleeman N, Hockenhull J, Dundar Y. The clinical effectiveness and cost-effectiveness of the PROGENSA® prostate cancer antigen 3 assay and the Prostate Health Index in the diagnosis of prostate cancer: a systematic review and economic evaluation. Health Technol Assess. 2015 Oct;19(87):i-xxxi, 1-191.

实验方案

计算器摩尔计算器总药量计算器工作液计算器
储存液制备
- 1 mg
- 5 mg
- 10 mg
- 1 mM
- 2.3614 mL
- 11.8068 mL
- 23.6137 mL
- 5 mM
- 0.4723 mL
- 2.3614 mL
- 4.7227 mL
- 10 mM
- 0.2361 mL
- 1.1807 mL
- 2.3614 mL

技术信息

CAS号

1690172-25-8

储存条件

粉末: Sealed in dry,2-8°C

液体: -20°C:3-6 月 -80°C:12月

分子式

C23H26FN5O2

运输

蓝冰

分子量

423.48

别名

MDK-2258

溶解度

DMSO	18.0 mg/mL (42.5 mM)
Water	insoluble

动物实验配方

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