Description:
            TK-453 (TK453) is a potent, selective SHP2 allosteric inhibitor with IC50 of 18.76 and 179 nM for SHP2-WT and SHP2-E76K, respectively.TK-453 has strong inhibitory effect on the enzyme activity of the SHP2-WT, and does not inhibit the activity of the SHP2-PTP catalytic domain, and homologues (SHP1 and PTP1B).TK-453 binds SHP2-WT (KD=150 nM) and SHP2-E76K, higher affinity with SHP2 than SHP099.TK-453 binds in the allosteric binding pocket at the junction of three domains and stabilizes the autoinhibition conformation of SHP2.TK-453 alleviates imiquimod (IMQ)-induced inflammation in macrophages, inhibits the phosphorylation levels of p-IKKα/β and p-p65.TK-453 significantly ameliorates imiquimod-triggered skin-like inflammation in mice via inhibition of IL-23/Th17 axis.
         
    
    
        Handling:
        
            Providing storage is as stated on the product vial and the vial is kept tightly sealed, the product can be stored for up to 24 months.
            Wherever possible, you should prepare and use solutions on the same day. However, if you need to make up stock solutions in advance, 
            we recommend that you store the solution as aliquots in tightly sealed vials at -20°C. Generally, these will be useable for up to one 
            month. Before use, and prior to opening the vial we recommend that you allow your product to equilibrate to room temperature for at 
            least 1 hour.