BQR-695

• CAT Number: I013052
• CAS Number: 1513879-21-4
• Molecular Formula: C₁₉H₂₀N₄O₃
• Molecular Weight: 352.39
• Purity: ≥95%
• Target: PI4K
• Solubility: DMSO: 100 mg/mL
• IUPAC Name: 2-[[7-(3,4-dimethoxyphenyl)quinoxalin-2-yl]amino]-N-methylacetamide
• InChI: InChI=1S/C19H20N4O3/c1-20-19(24)11-22-18-10-21-14-6-4-12(8-15(14)23-18)13-5-7-16(25-2)17(9-13)26-3/h4-10H,11H2,1-3H3,(H,20,24)(H,22,23)
• InChIKey: LYPCULYCGFOIDA-UHFFFAOYSA-N
• SMILES: CNC(=O)CNC1=CN=C2C=CC(=CC2=N1)C3=CC(=C(C=C3)OC)OC

BQR-695 (CAS 1513879-21-4) is a potent inhibitor of phosphatidylinositol 4-kinase IIIβ (PI4KIIIβ). It exhibits significant inhibitory activity against both human PI4KIIIβ and the Plasmodium variant of PI4KIIIβ, with reported IC50 values of 80 nM and 3.5 nM, respectively. By selectively targeting PI4KIIIβ, BQR-695 interferes with the production of phosphatidylinositol 4-phosphate (PI4P), a key lipid signaling molecule involved in various cellular processes. The pharmacological activity and potent inhibition of PI4KIIIβ make BQR-695 a potential candidate for further research and development in areas such as antimalarial therapy and other PI4KIIIβ-related diseases.

Reference

1. Protein Sci. 2016 Apr;25(4):826-39. doi: 10.1002/pro.2879. Epub 2016 Feb 1.
Using hydrogen deuterium exchange mass spectrometry to engineer optimized constructs for crystallization of protein complexes: Case study of PI4KIIIβ with Rab11.
Fowler ML(1), McPhail JA(1), Jenkins ML(1), Masson GR(2), Rutaganira FU(3), Shokat KM(3), Williams RL(2), Burke JE(1).
Author information:
(1)Department of Biochemistry and Microbiology, University of Victoria, British Columbia, V8P 5C2, Canada. (2)MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge, CB2 0QH, United Kingdom. (3)Howard Hughes Medical Institute and Department of Cellular and Molecular Pharmacology, University of California, San Francisco (UCSF), California, 94158.
The ability of proteins to bind and interact with protein partners plays fundamental roles in many cellular contexts. X-ray crystallography has been a powerful approach to understand protein-protein interactions; however, a challenge in the crystallization of proteins and their complexes is the presence of intrinsically disordered regions. In this article, we describe an application of hydrogen deuterium exchange mass spectrometry (HDX-MS) to identify dynamic regions within type III phosphatidylinositol 4 kinase beta (PI4KIIIβ) in complex with the GTPase Rab11. This information was then used to design deletions that allowed for the production of diffraction quality crystals. Importantly, we also used HDX-MS to verify that the new construct was properly folded, consistent with it being catalytically and functionally active. Structures of PI4KIIIβ in an Apo state and bound to the potent inhibitor BQR695 in complex with both GTPγS and GDP loaded Rab11 were determined. This hybrid HDX-MS/crystallographic strategy revealed novel aspects of the PI4KIIIβ-Rab11 complex, as well as the molecular mechanism of potency of a PI4K specific inhibitor (BQR695). This approach is widely applicable to protein-protein complexes, and is an excellent strategy to optimize constructs for high-resolution structural approaches.