2222354-57-4

2222354-57-4 structure

Name: HG-12-6
Chemical Name: HG-12-6
CAS Number: 2222354-57-4
Molecular Formula: C₂₉H₂₇F₃N₆O₂S
Molecular Weight: 580.63
Catalog: Signaling Pathways Immunology/Inflammation IRAK
Create Date: 2020-01-19 14:45:17
Modify Date: 2024-01-10 18:17:46
HG-12-6 is a small-molecule inhibitor that bind preferentially to unphosphorylated IRAK4 with IC50 of 165.1 nM, displays 15-fold selectivity over phosphorylated IRAK4 (IC50=2876 nM); binds as type II inhibitor with IRAK4 in a “DFG-out” conformation.

Name	HG-12-6

Description	HG-12-6 is a small-molecule inhibitor that bind preferentially to unphosphorylated IRAK4 with IC50 of 165.1 nM, displays 15-fold selectivity over phosphorylated IRAK4 (IC50=2876 nM); binds as type II inhibitor with IRAK4 in a “DFG-out” conformation.
Related Catalog	Signaling Pathways >> Immunology/Inflammation >> IRAK Research Areas >> Inflammation/Immunology Signaling Pathways >> Protein Tyrosine Kinase/RTK >> IRAK
Target	IRAK4:165 nM (IC50, Unphosphorylated inactive IRAK4 ) IRAK4:2876 nM (IC50, Phosphorylated active IRAK4 )
In Vitro	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].
References	[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.

Molecular Formula	C₂₉H₂₇F₃N₆O₂S
Molecular Weight	580.63