HG-12-6 

HG-12-6 is a type II inhibitor of IRAK4. HG-12-6 shows preferential binding to unphosphorylated inactive IRAK4 with an IC₅₀ of 165 nM. HG-12-6 can modulate IRAK4 activity in autoimmunity and inflammation^[1].

The in-house compound HG-12-6 has a similar chemical scaffold as Ponatinib. The most differentiating components are the head of the inhibitor and the lack of a methyl substituent on ring A. Without the methyl substituent on ring A, the entire HG-12-6 molecule shifts inward to the ATP pocket in comparison with the binding mode of Ponatinib^[1].
HG-12-6 has a better binding affinity for the unphosphorylated inactive IRAK4 kinase domain (IC₅₀ of 165 nM) than the phosphorylated active IRAK4 kinase domain (IC₅₀ of 2876 nM)^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

580.62

C₂₉H₂₇F₃N₆O₂S

2222354-57-4

O=C(NC1=CC=C(CN2CCNCC2)C(C(F)(F)F)=C1)C3=CC=CC(C4=CC=C5C(SC(NC(C6CC6)=O)=N5)=N4)=C3

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• [1]. Wang L, et al. Conformational flexibility and inhibitor binding to unphosphorylated interleukin-1 receptor-associated kinase 4 (IRAK4). J Biol Chem. 2019 Mar 22;294(12):4511-4519.  [Content Brief]