PAIR2
PAIR2 is a highly selective inhibitor targeting the kinase domain of human IRE1α, with a Ki value of 8.8 nM against human IRE1α. PAIR2 fully occupies the ATP-binding site of the IRE1α kinase domain, partially antagonizes the ribonuclease activity of IRE1α, specifically inhibits regulated IRE1α-dependent decay (RIDD) and its mediated substrate cleavage, while preserving the splicing function of Xbp1 mRNA. PAIR2 also promotes the differentiation of B cells into plasma cells, blocks IRE1α-induced cell apoptosis, and restores the expression of Fgfr2 mRNA in AT2 cells. PAIR2 effectively reaches a steady-state concentration in the lung tissues of Mus musculus, and serves as an important tool for investigating the function of the IRE1α signaling pathway in diseases such as pulmonary fibrosis.
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- CAS No.: 2771006-54-1
- 화학식: C27H26F4N6O3S
- 분자량:590.59
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보관:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
- 순도&문서
- References
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Help & FAQs
Biological Activity
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IRE1α 8.8 nM (Ki) |
FGFR2 |
PAIR2 (1-10 μM; 1 h + 6 h doxycycline (HY-N0565)) dose-dependently blocks doxycycline-induced autophosphorylation of IRE1α in INS-1::PCMV/2xTetO cells[1].
PAIR2 (0.5-10 μM; 1 h+2 h DTT (HY-15917)) maintains XBP1 mRNA splicing in parental INS-1 cells subjected to DTT stress[1].
PAIR2 (2 μM; 24 h Thapsigargin (HY-13433)) rescues Fgfr2 mRNA expression in serum-free, feeder-free primary mouse AT2 organoids under Thapsigargin stress, while preserving IRE1α-mediated Xbp1 splicing[2].
PAIR2 (2 μM; 3-d) fails to prevent the conversion of primary serum-free, feeder-free mouse AT2 cells to DATCs when pemigatinib directly blocks the Fgfr signaling pathway[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:INS-1::PCMV/2xTetO rat insulinoma cells (doxycycline-inducible IRE1α overexpression)
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Concentration:1, 3, 10 μM
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Incubation Time:1 h (PAIR2 pre-incubation); 6 h (doxycycline treatment)
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Result:Dose-dependently blocked doxycycline-induced IRE1α autophosphorylation, reducing phosphorylated IRE1α levels to near baseline at concentrations ≥3 μM, with equivalent potency to KIRA8.
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Cell Line:parent INS-1 rat insulinoma cells
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Concentration:0.5, 1, 3, 10 μM
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Incubation Time:1 h (PAIR2 pre-incubation); 2 h (DTT treatment)
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Result:Preserved DTT-induced XBP1 mRNA splicing at all tested concentrations, with no significant reduction in splicing percentage relative to DTT-only treated cells (all P values > 0.05, non-significant).
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6 (10-20 week-old, both male and female, bleomycin-induced pulmonary fibrosis)[2]
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Dosage:30 mg/kg
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Administration:i.p.; twice daily; starting 1 day before bleomycin exposure and continuing through study end
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Result:Reduced fraction of trace+Krt8+ / trace+ cells compared to vehicle control at day 10 post-bleomycin exposure.
Significantly lowered lung hydroxyproline content and reduced fibrillar collagen deposition via picrosirius red staining at day 14 post-bleomycin exposure.
Derepressed expression of canonical RIDD target Bloc1s1 in lung tissue.
Did not significantly affect Xbp1 splicing.
Chemical Information
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CAS No. 2771006-54-1
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분자량 590.59
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화학식 C27H26F4N6O3S
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SMILES
CC(C(F)=C(NS(CC(F)(F)F)(=O)=O)C1=C2C=CC=C1)=C2OC3=NC=CC=C3C4=NC(N[C@H]5CCCNC5)=NC=C4
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선적
Room temperature in continental US; may vary elsewhere.
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보관
Please store the product under the recommended conditions in the Certificate of Analysis.
순도&문서
References
[1]. Feldman HC, et al. ATP-competitive partial antagonists of the IRE1α RNase segregate outputs of the UPR. Nat Chem Biol. 2021;17(11):1148-1156. [Content Brief]
[2]. Auyeung VC, et al. Pharmacologic inhibition of IRE1α-dependent decay protects alveolar epithelial identity and prevents pulmonary fibrosis in mice. J Clin Invest. 2025;135(20):e184522. Published 2025 Oct 15. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
PAIR2 Related Classifications
HY-145425 Related Classifications
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