WEHI-345 is a potent and selective RIPK2 inhibitor which shows NOD signalling events yet prevents inflammatory cytokine production. WEHI-345 delays RIPK2 ubiquitylation and NF-κB activation downstream of NOD engagement. Despite only delaying NF-κB activation on NOD stimulation, WEHI-345 prevents cytokine production in vitro and in vivo and ameliorates experimental autoimmune encephalomyelitis in mice.
Chemical Formula: C22H23N7O
Exact Mass: 401.1964
Molecular Weight: 401.474
Elemental Analysis: C, 65.82; H, 5.77; N, 24.42; O, 3.99
Chemical Name: N-(2-(4-amino-3-(p-tolyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-2-methylpropyl)isonicotinamide
InChi Code: InChI=1S/C22H23N7O/c1-14-4-6-15(7-5-14)18-17-19(23)26-13-27-20(17)29(28-18)22(2,3)12-25-21(30)16-8-10-24-11-9-16/h4-11,13H,12H2,1-3H3,(H,25,30)(H2,23,26,27)
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
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.
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.
Nachbur U, Stafford CA, Bankovacki A, Zhan Y, Lindqvist LM, Fiil BK, Khakham Y, Ko HJ, Sandow JJ, Falk H, Holien JK, Chau D, Hildebrand J, Vince JE, Sharp PP, Webb AI, Jackman KA, Mühlen S, Kennedy CL, Lowes KN, Murphy JM, Gyrd-Hansen M, Parker MW, Hartland EL, Lew AM, Huang DC, Lessene G, Silke J. A RIPK2 inhibitor delays NOD signalling events yet prevents inflammatory cytokine production. Nat Commun. 2015 Mar 17;6:6442. doi: 10.1038/ncomms7442. PubMed PMID: 25778803.
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