158985-25-2Relevant articles and documents
Affinity-Based Selectivity Profiling of an In-Class Selective Competitive Inhibitor of Acyl Protein Thioesterase 2
Won, Sang Joon,Eschweiler, Joseph D.,Majmudar, Jaimeen D.,Chong, Fei San,Hwang, Sin Ye,Ruotolo, Brandon T.,Martin, Brent R.
, p. 215 - 220 (2017)
Activity-based protein profiling (ABPP) has revolutionized the discovery and optimization of active-site ligands across distinct enzyme families, providing a robust platform for in-class selectivity profiling. Nonetheless, this approach is less straightfo
ADENOSINE A2A RECEPTOR ANTAGONISTS AND USES THEREOF
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Paragraph 00372, (2021/02/12)
Disclosed herein are compounds, compositions, and methods for modulating the A2A2A adenosine receptor with the compounds and compositions disclosed herein. Also described are methods of treating diseases or disorders that are mediated by the A
Truncated Itraconazole Analogues Exhibiting Potent Anti-Hedgehog Activity and Improved Drug-like Properties
Wen, Jiachen,Chennamadhavuni, Divya,Morel, Shana R.,Hadden, M. Kyle
, p. 1290 - 1295 (2019/09/30)
We conducted a structure-activity relationship study to explore simplified analogues of the itraconazole (ITZ) scaffold for their ability to inhibit the hedgehog (Hh) signaling pathway. These analogues were based on exploring the effects of chemical modifications to the linker and triazolone/side chain region of ITZ. Analogue 11 was identified as the most potent compound in our first generation, with an IC50 value of 81 nM in a murine Hh-dependent basal cell carcinoma. Metabolic identification studies led us to identify truncated piperazine (26) as the major metabolite in human liver microsomes (HLMs) and an improved Hh pathway inhibitor (IC50 = 22 nM). This work verifies that continued truncation of the ITZ scaffold is a practical method to maintain potent anti-Hh activity while also reducing the molecular weight for the ITZ scaffold and achieving improved pharmacokinetic properties.