WEHI-345

SKU: orb1226463

Description

A potent and selective RIPK2 inhibitor with IC50/Kd of 130/46 nM; displays negligible activity (>10 uM) against RIPK1, RIPK4 and RIPK5; delays RIPK2 ubiquitylation and NF-κB activation downstream of NOD engagement; prevents cytokine production in vitro and in vivo and ameliorates experimental autoimmune encephalomyelitis in mice.

Key Properties

• CAS Number: 1354825-58-3
• MW: 401.4643
• Purity: >98% (HPLC)
• Formula: C₂₂H₂₃N₇O
• SMILES: O=C(NCC(C)(N1N=C(C2=CC=C(C)C=C2)C3=C(N)N=CN=C31)C)C4=CC=NC=C4
• Target: RIP kinase
• Solubility: DMSO: ≥ 32 mg/mL

Bioactivity

• In Vivo:
  WEHI-345 (20 mg/kg; intraperitoneal injection; twice daily; for 6 days; C57BL/6 male mice) treatment reduces disease score, inflammatory infiltrate, histological score and recruitment of dendritic cells to the site of inflammation. And improves body weight and reduces cytokine and chemokine levels, indicating an overall improvement of the condition in experimental autoimmune encephalomyelitis (EAE)-induced wild-type C57Bl/6 mice. Animal model: C57BL/6 male mice (8-week-old). Dosage: 20 mg/kg. Administration: Intraperitoneal injection; twice daily; for 6 days. Result: Reduced disease score, inflammatory infiltrate, histological score and recruitment of dendritic cells to the site of inflammation. And improved body weight and reduced cytokine and chemokine levels.
• In Vitro:
  WEHI-345 (500 nM; Raw 267.4 cells) is able to inhibit MDP-induced autophosphorylation activity of RIPK2 in cells. WEHI-345 (500 nM; 0 hour, 2 hours, 4 hours, 8 hours; BMDMs or THP-1 cells) potently blocks MDP-induced transcription of the inflammatory mediators TNF and interleukin-6 (IL-6) in bone marrow-derived macrophages (BMDMs). In THP-1 cells, WEHI-345 reduces mRNA levels of NF-kB targets such as TNF, IL-8, IL-1b and A20. Western blot analysis. Cell line: Raw 267.4 cells Concentration: 500 nM. Incubation time: Result: Inhibited MDP-induced autophosphorylation activity of RIPK2 in cells. RT-PCR Cell line: BMDMs or THP-1 cells. Concentration: 500 nM. Incubation time: 0 hour, 2 hours, 4 hours, 8 hours. Result: Blocked MDP-induced transcription of the inflammatory mediators TNF and interleukin-6 (IL-6) in BMDMs. And reduced mRNA levels of NF-kB targets in THP-1 cells.

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

WEHI-345 | WEHI345 | WEHI 345

Quick Database Links

Gene Symbol

RIP kinase