62054-67-5

62054-67-5 structure

Name: THS-044
Chemical Name: THS-044
CAS Number: 62054-67-5
Molecular Formula: C₁₁H₁₂F₃N₃O₃
Molecular Weight: 291.227
Catalog: Signaling Pathways Metabolic Enzyme/Protease HIF/HIF Prolyl-Hydroxylase
Create Date: 2018-06-22 15:37:53
Modify Date: 2024-01-02 18:53:21
THS-044 binding stabilizes the HIF2α PAS-B folded state, for regulating HIF2 activity in endogenous and clinical settings.Target: HIF2αLimited trypsin proteolysis reveals that both apo and THS-044-bound protein are efficiently cut at R330 in the extended HI loop. In the THS-044 bound state, there appears no additional proteolysis at the remaining candidate trypsin sites. In contrast, these THS-044-protected sites are protease accessible in the unliganded protein, leading its complete degradation. In parallel, NMR-based deuterium exchange measurements revealed a dramatic stabilization of the THS-044-bound protein β-sheet, with some sites experiencing 100-fold enhanced protection factors relative to the ligand-free protein.

Name	THS-044
Synonyms	N-[2-Nitro-4-(trifluoromethyl)phenyl]-4-morpholinamine 4-Morpholinamine, N-[2-nitro-4-(trifluoromethyl)phenyl]- N-[2-nitro-4-(trifluoromethyl)phenyl]morpholin-4-amine

Description	THS-044 binding stabilizes the HIF2α PAS-B folded state, for regulating HIF2 activity in endogenous and clinical settings.Target: HIF2αLimited trypsin proteolysis reveals that both apo and THS-044-bound protein are efficiently cut at R330 in the extended HI loop. In the THS-044 bound state, there appears no additional proteolysis at the remaining candidate trypsin sites. In contrast, these THS-044-protected sites are protease accessible in the unliganded protein, leading its complete degradation. In parallel, NMR-based deuterium exchange measurements revealed a dramatic stabilization of the THS-044-bound protein β-sheet, with some sites experiencing 100-fold enhanced protection factors relative to the ligand-free protein.
Related Catalog	Signaling Pathways >> Metabolic Enzyme/Protease >> HIF/HIF Prolyl-Hydroxylase Research Areas >> Cancer
References	[1]. Motto I, et al. New aryl hydrocarbon receptor homology model targeted to improve docking reliability. J Chem Inf Model. 2011 Nov 28;51(11):2868-2881. [2]. Scheuermann TH, et al. Artificial ligand binding within the HIF2alpha PAS-B domain of the HIF2 transcription factor. Proc Natl Acad Sci U S A. 2009 Jan 13;106(2):450-455.