Kira8

SKU: orb1940793

Description

Kira8 is a mono-selective IRE1α inhibitor that allosterically attenuates IRE1α RNase activity (IC50: 5.9 nM).(In Vitro):Kira8 more effectively causes IRE1α-driven apoptosis in INS-1 cells than KIRA6 and also reverses XBP1 splicing promoted by GNF-2. Kira8 blocks IRE1α oligomerization and effectively inhibits IRE1α RNase activity against XBP1 and Ins2 RNAs.(In Vivo):One week of treatment of pre-diabetic NODs mice with Kira8 (50 mg/kg; i.p.; once a day) causes obvious reductions in islet XBP1 splicing and TXNIP mRNAs. It also preserves Ins1/Ins2, BiP, and MANF mRNAs. Male Ins2+/Akita mice are injected i.p. with KIRA8 (50 mg/kg; daily; for 35 days), obviously reduction of hyperglycemia becomes apparent over several weeks.

Key Properties

• CAS Number: 1630086-20-2
• MW: 601.12
• Purity: >98% (HPLC)
• Formula: C₃₁H₂₉ClN₆O₃S
• SMILES: Cc1ccc2c(NS(=O)(=O)c3ccccc3Cl)cccc2c1Oc1ncccc1-c1ccnc(N[C@H]2CCCNC2)n1
• Target: antiprotozoal
• Solubility: In Vitro: Ethanol : 76.92 mg/mL (127.96)

Bioactivity

• In Vivo:
  Male Ins2+/Akita mice are injected i.p. with KIRA8 (50 mg/kg; daily; for 35 days), significant reduction of hyperglycemia become apparent over several weeks. One week treatment of pre-diabetic NODs mice with Kira8 (50 mg/kg; i.p.; once a day) leads to significant reductions in islet XBP1 splicing and TXNIP mRNAs, and preserves Ins1/Ins2, BiP and MANF mRNAs. Animal model: Male Ins2+/Akita mice. Dosage: 50 mg/kg. Administration: Injected i.p.; daily; for 35 days. Result: Significant reduction of hyperglycemia became apparent over several weeks.
• In Vitro:
  Kira8 blocks IRE1α oligomerization, and potently inhibits IRE1α RNase activity against XBP1 and Ins2 RNAs. Kira8 more potently reduces IRE1α-driven apoptosis in INS-1 cells than KIRA6 and also reverses XBP1 splicing promoted by GNF-2.

Storage & Handling

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

Alternative Names

AMG-18

Quick Database Links

Gene Symbol

antiprotozoal