1628317-85-0Relevant articles and documents
METHODS OF PROMOTING BETA CELL PROLIFERATION
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Paragraph 00155, (2018/06/30)
The present disclosure provides methods of promoting proliferation of a pancreatic cell. The methods are useful for the treatment of diabetes and other diseases characterized by impaired glucose tolerance.
INHIBITORS OF THE MENIN-MLL INTERACTION
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, (2017/07/14)
The present invention is directed to inhibitors of the interaction of menin with MLL and MLL fusion proteins, pharmaceutical compositions containing the same, and their use in the treatment of cancer and other diseases mediated by the menin-MLL interaction.
Property Focused Structure-Based Optimization of Small Molecule Inhibitors of the Protein-Protein Interaction between Menin and Mixed Lineage Leukemia (MLL)
Borkin, Dmitry,Pollock, Jonathan,Kempinska, Katarzyna,Purohit, Trupta,Li, Xiaoqin,Wen, Bo,Zhao, Ting,Miao, Hongzhi,Shukla, Shirish,He, Miao,Sun, Duxin,Cierpicki, Tomasz,Grembecka, Jolanta
, p. 892 - 913 (2016/02/23)
Development of potent small molecule inhibitors of protein-protein interactions with optimized druglike properties represents a challenging task in lead optimization process. Here, we report synthesis and structure-based optimization of new thienopyrimidine class of compounds, which block the protein-protein interaction between menin and MLL fusion proteins that plays an important role in acute leukemias with MLL translocations. We performed simultaneous optimization of both activity and druglike properties through systematic exploration of substituents introduced to the indole ring of lead compound 1 (MI-136) to identify compounds suitable for in vivo studies in mice. This work resulted in the identification of compound 27 (MI-538), which showed significantly increased activity, selectivity, polarity, and pharmacokinetic profile over 1 and demonstrated a pronounced effect in a mouse model of MLL leukemia. This study, which reports detailed structure-activity and structure-property relationships for the menin-MLL inhibitors, demonstrates challenges in optimizing inhibitors of protein-protein interactions for potential therapeutic applications.
THIENOPYRIMIDINE AND THIENOPYRIDINE COMPOUNDS AND METHODS OF USE THEREOF
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Paragraph 00427, (2016/04/20)
The present disclosure provides compounds and methods for inhibiting the interaction of menin with its upstream or downstream signaling molecules including but not limited to MLL1, MLL2 and MLL-fusion oncoproteins. Compounds of the disclosure may be used
COMPOSITIONS COMPRISING THIENOPYRIMIDINE AND THIENOPYRIDINE COMPOUNDS AND METHODS OF USE THEREOF
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Paragraph 0172, (2014/09/29)
The present invention relates generally to thienopyrimidine and thienopyridine class compounds and methods of use thereof. In particular embodiments, the present invention provides compositions comprising thienopyrimidine class compounds and methods of us