- Systematic Investigation of the Permeability of Androgen Receptor PROTACs
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Bifunctional molecules known as PROTACs simultaneously bind an E3 ligase and a protein of interest to direct ubiquitination and clearance of that protein, and they have emerged in the past decade as an exciting new paradigm in drug discovery. In order to investigate the permeability and properties of these large molecules, we synthesized two panels of PROTAC molecules, constructed from a range of protein-target ligands, linkers, and E3 ligase ligands. The androgen receptor, which is a well-studied protein in the PROTAC field was used as a model system. The physicochemical properties and permeability of PROTACs are discussed.
- Scott, Duncan E.,Rooney, Timothy P. C.,Bayle, Elliott D.,Mirza, Tashfina,Willems, Henriette M. G.,Clarke, Jonathan H.,Andrews, Stephen P.,Skidmore, John
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supporting information
p. 1539 - 1547
(2020/06/25)
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- Production method of novel imidazoline derivative
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The invention relates to a production method of a novel imidazoline derivative, in particular to a production method of a novel intermediate, especially a compound 44, for producing an imidazoline derivative, and a novel intermediate compound b. The novel production method is low in cost, high in yield and suitable for industrial production.
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Paragraph 0063; 0067-0069
(2020/02/10)
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- PROTEIN-PROTEIN INTERACTION INDUCING TECHNOLOGY
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The present disclosure is based on the surprising and unexpected discovery that a ligand molecule with certain characteristics is able to bind to two protein molecules simultaneously and recruit them to form a transient or stable protein-protein interaction complex. The protein-protein interaction and other cross-domain interactions gained in this process contribute additional stabilization energy to the complex beyond the combination of the binary binding energies, and therefore, largely increase the binding potency of the ligand. Accordingly, the present disclosure provides a Protein-Protein Interaction Inducing Technology (PPIIT), which includes a method to design and identify the tripartite or bifunctional compounds and use such compounds to induce protein-protein interactions in various contexts. The present disclosure also provides a composition for the purpose of inducing protein-protein interactions.
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Paragraph 0187; 0190
(2017/10/17)
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- IMIDAZOLINE DERIVATIVES, PREPARATION METHODS THEREOF, AND THEIR APPLICATIONS IN MEDICINE
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New imidazoline derivatives represented by formula (I), preparation methods thereof, pharmaceutical compositions comprising such derivatives, and applications of such derivatives in preparing androgen receptor antagonists and medicaments for treating diseases such as prostate cancer.
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- IMIDAZOLINE DERIVATIVES, PREPARATION METHODS THEREOF, AND THEIR APPLICATIONS IN MEDICINE
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New imidazoline derivatives represented by formula (I): preparation methods thereof, pharmaceutical compositions comprising such derivatives, and applications of such derivatives in preparing androgen receptor antagonists and medicaments for treating diseases such as prostate cancer are described.
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- Structure-activity relationship for thiohydantoin androgen receptor antagonists for castration-resistant prostate cancer (CRPC)
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A structure-activity relationship study was carried out on a series of thiohydantoins and their analogues 14 which led to the discovery of 92 (MDV3100) as the clinical candidate for the treatment of hormone refractory prostate cancer.
- Jung, Michael E.,Ouk, Samedy,Yoo, Dongwon,Sawyers, Charles L.,Chen, Charlie,Tran, Chris,Wongvipat, John
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experimental part
p. 2779 - 2796
(2010/09/05)
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- DIARYLHYDANTOIN COMPOUNDS
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The present invention relates to diarylhydantoin compounds, including diarylthiohydantoins, and methods for syntheszing them and using them in the treatment of hormone refractory prostate cancer.
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Page/Page column 24
(2008/06/13)
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