KIRA6

SKU: orb1220060

Description

KIRA6 is an effective inhibitor of IRE1α RNase kinase (IC50: 0.6 μM). It can trigger an apoptotic response.KIRA6 (10-1000 nM, 72 hours) strongly compromises the viability of the KIT-dependent cell line HMC-1.1 at the low nM concentration, in a manner that coincided with KIT blockade. KIRA6 (1nM-100μM) bounds to the cytoplasmic domain of KIT with a Kd value of 10.8 μM. KIRA6 (10-1000 nM, 1 hour) reduces signaling output of KIT, including the phosphorylation of KIT as well as its downstream signaling modules, PSTAT5 and phosphorylated ERK1/2.KIRA6 (1 μM, 0-48 hours) inhibits Ins1 mRNA decay from IRE1α hyperactivation in a dose-dependent manner. KIRA6 (0.1-10μM, 72 hours) dose-dependently reduces 1NM-PP1 potentiation of Ins1 apoptosis during ER stress in a dose-dependent manner [2].KIRA6 (intraperitoneal injection; 5 mg/kg; 37 days) shows significant amelioration of random glucose levels over several weeks compared to the vehicle, both fed ad lib. KIRA6 (i.p, 5 mg/kg, 21 or 18 days post injections) increases both plasma insulin and C-peptide levels, remains insulin-positive islet areas at a high level after stopping injections in the Akita Mouse.

Key Properties

• CAS Number: 1589527-65-0
• MW: 518.53
• Purity: >98% (HPLC)
• Formula: C₂₈H₂₅F₃N₆O
• SMILES: CC(C)(C)C1=NC(=C2N1C=CN=C2N)C1=CC=C(NC(=O)NC2=CC=CC(=C2)C(F)(F)F)C2=CC=CC=C12
• Target: IRE1α
• Solubility: DMSO:5 mg/mL (9.64 mM);Ethanol:2 mg/mL (3.86 mM; Need ultrasonic)

Bioactivity

• In Vivo:
  Animal model: Male Ins2+/Akita mice. Dosage: 5 mg/kg. Administration: Intraperitoneal injection; 5 mg/kg; 21 or 18 days postinjections. Result: Attenuates b cell functional loss, increased insulin levels.
• In Vitro:
  Cell Viability Assay Cell line: HMC-1.1 cells Concentration: 10 nM, 30 nM, 100 nM, 300 nM, 1000 nM. Incubation time: 72 hours. Result: Inhibited cell viability from 30 nM. Western blot analysis. Cell line: HMC-1.1 cells Concentration: 10 nM, 30 nM, 100 nM, 300 nM, 1000 nM. Incubation time: 1 hours. Result: Reduced expression of phosphorylated KIT, STAT5 and ERK1/2.RT-PCR Cell line: INS-1 IRE1α (WT) cells. Concentration: 1 μM. Incubation time: 0 hour, 12 hours, 24 hours, 48 hours. Result: Inhibited Ins1 mRNA expression. Apoptosis Analysis Cell line: INS-1 IRE1α (WT) cells. Concentration: 1-10 μM. Incubation time: 72 hours. Result: Reduced 1NM-PP1 potentiation of Ins1 apoptosis during ER stress.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Quick Database Links

Gene Symbol

IRE1α