KIRA6 - IRE1 抑制劑 - 生命科學(xué)試劑 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEKIRA6Cat. No.: HY-19708CAS No.: 1589527-65-0分式: CHFNO分量: 518.53作靶點(diǎn): IRE1作通路: Cell Cycle/DNA Damage儲(chǔ)存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 5 mg/mL (9.64 mM)Ethanol : 2 mg/mL (3.86 mM

2、; Need ultrasonic)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲(chǔ)備液1 mM 1.9285 mL 9.6426 mL 19.2853 mL5 mM 0.3857 mL 1.9285 mL 3.8571 mL10 mM - - -請(qǐng)根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲(chǔ)備液，并請(qǐng)注意儲(chǔ)備液的保存式和期限。體內(nèi)實(shí)驗(yàn)請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥式選擇適當(dāng)?shù)娜芙獍?，配制前?qǐng)先配制澄的儲(chǔ)備液，再依次添加助溶劑(為保證實(shí)驗(yàn)結(jié)果的可靠性，體內(nèi)實(shí)驗(yàn)的作液，建議您現(xiàn)

3、現(xiàn)配，當(dāng)天使；澄的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；以下溶劑前的百分 指該溶劑在您配制終溶液中的體積占)：1. 請(qǐng)依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 0.5 mg/mL (0.96 mM); Clear solution2. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 0.5 mg/mL (0.96 mM); Clear solution1/3 Master of Small Molecules 您邊的抑制劑師www.MedChem

4、E3. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 0.5 mg/mL (0.96 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 KIRA6，分 IRE1 RNase 激酶抑制劑，IC50 值為0.6 M。 KIRA6 可以觸發(fā)細(xì)胞凋亡 (apoptotic) 反應(yīng)。IC50 & Target IC50: 0.6 M (IRE1 RNase kinase) 2體外研究KIRA6 (1nM-100M) bounds to the cytoplasmic domain of KIT with a Kd value o

5、f 10.8 M 1.KIRA6 (10-1000 nM; 72 hours) strongly compromises the viability of the KIT-dependent cell line HMC-1.1 at the low nMconcentration, in a manner that coincided with KIT blockade 1.KIRA6 (10-1000 nM; 1 hour) reducessignaling output of KIT, including the phosphorylation of KIT as well as its

6、downstream signaling modules,PSTAT5 and phosphorylated ERK1/2 1.KIRA6 (1 M; 0-48 hours) inhibits Ins1 mRNA decay from IRE1hyperactivation at a dose-dependent manner 2.KIRA6 (0.1-10M; 72 hours) dose-dependently reduces1NM-PP1 potentiation of Ins1 apoptosis during ER stress in a dose-dependent manner

7、2.Cell Viability Assay 1Cell Line: HMC-1.1 cellsConcentration: 10 nM, 30 nM, 100 nM, 300 nM, 1000 nMIncubation Time: 72 hoursResult: Inhibited cell viability from 30 nM.Western Blot Analysis 1Cell Line: HMC-1.1 cellsConcentration: 10 nM, 30 nM, 100 nM, 300 nM, 1000 nMIncubation Time: 1 hoursResult:

8、Reduced expression of phosphorylated KIT, STAT5 and ERK1/2.RT-PCR 2Cell Line: INS-1 IRE1 (WT) cellsConcentration: 1 MIncubation Time: 0 hour, 12 hours, 24 hours, 48 hoursResult: Inhibited Ins1 mRNA expression.Apoptosis Analysis 22/3 Master of Small Molecules 您邊的抑制劑師www.MedChemECell Line: INS-1 IRE1

9、(WT) cellsConcentration: 1-10 MIncubation Time: 72 hoursResult: Reduced 1NM-PP1 potentiation of Ins1 apoptosis during ER stress.體內(nèi)研究 KIRA6 (intraperitoneal injection; 5 mg/kg; 37 days) shows significant amelioration of random glucose levelsover several weeks compared to vehicle, both fed ad lib 2.KI

10、RA6 (intraperitoneal injection; 5 mg/kg; 21 or18 days postinjections) increases both plasma insulin and C-peptide levels, remains insulin-positive isletareas at high level after stopping injections in the Akita Mouse 2.Animal Model: Male Ins2+/Akita mice 2Dosage: 5 mg/kgAdministration: Intraperitone

11、al injection; 5 mg/kg; 21 or 18 days postinjectionsResult: Attenuates b cell functional loss, increased insulin levels.戶使本產(chǎn)品發(fā)表的科研獻(xiàn) Science. 2019 Jul 19;365(6450). pii: eaau6499.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Mahameed M,et al. The unfolded protein response modulators GSK2606414 and KIRA6 are potent KIT inhibitors. Cell Death Dis. 2019Apr 1;10(4):300.2. Ghosh R, et al. Allosteric inhibition of the IRE1 RNase preserves cell viability and function during endoplasmic reticulum stress. Cell.2014 Jul 31;158(3):534-48.McePdfHeightCaution: Pro