36778-16-2Relevant academic research and scientific papers
CYCLIC COMPOUNDS AND METHODS OF USING SAME
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Page/Page column 585, (2021/07/02)
The present application relates to compounds of Formula (I), as defined herein, and pharmaceutically acceptable salts thereof which are MALT1 inhibitors. The present application also describes pharmaceutical composition comprising a compound of Formula (I), and pharmaceutically acceptable salts thereof, and methods of using the compounds and compositions for treating diseases, such as cancer, autoimmune disorders, and inflammatory disorders.
UREA COMPOUNDS AND COMPOSITIONS AS SMARCA2/BRM ATPASE INHIBITORS
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Page/Page column 27, (2020/03/05)
A compound of Formula (I), or a pharmaceutically acceptable salt thereof, is provided that has been shown to be useful for treating a BRM-mediated and/or BRG1-mediated disease or disorder: Formula (I) wherein R1 through R6 are as defined herein.
New geldanamycin derivatives with anti Hsp properties by mutasynthesis
Hermane, Jekaterina,Eichner, Simone,Mancuso, Lena,Schr?der, Benjamin,Sasse, Florenz,Zeilinger, Carsten,Kirschning, Andreas
supporting information, p. 5269 - 5278 (2019/06/07)
Mutasynthetic supplementation of the AHBA blocked mutant strain of S. hygroscopicus, the geldanamycin producer, with 21 aromatic and heteroaromatic amino acids provided new nonquinoid geldanamycin derivatives. Large scale (5 L) fermentation provided four new derivatives in sufficient quantity for full structural characterisation. Among these, the first thiophene derivative of reblastatin showed strong antiproliferative activity towards several human cancer cell lines. Additionally, inhibitory effects on human heat shock protein Hsp90α and bacterial heat shock protein from H. pylori HpHtpG were observed, revealing strong displacement properties for labelled ATP and demonstrating that the ATP-binding site of Hsps is the target site for the new geldanamycin derivatives.
Discovery of Orally Active Inhibitors of Brahma Homolog (BRM)/SMARCA2 ATPase Activity for the Treatment of Brahma Related Gene 1 (BRG1)/SMARCA4-Mutant Cancers
Papillon, Julien P. N.,Nakajima, Katsumasa,Adair, Christopher D.,Hempel, Jonathan,Jouk, Andriana O.,Karki, Rajeshri G.,Mathieu, Simon,M?bitz, Henrik,Ntaganda, Rukundo,Smith, Troy,Visser, Michael,Hill, Susan E.,Hurtado, Felipe Kellermann,Chenail, Gregg,Bhang, Hyo-Eun C.,Bric, Anka,Xiang, Kay,Bushold, Geoffrey,Gilbert, Tamara,Vattay, Anthony,Dooley, Julie,Costa, Emily A.,Park, Isabel,Li, Ailing,Farley, David,Lounkine, Eugen,Yue, Q. Kimberley,Xie, Xiaoling,Zhu, Xiaoping,Kulathila, Raviraj,King, Daniel,Hu, Tiancen,Vulic, Katarina,Cantwell, John,Luu, Catherine,Jagani, Zainab
, p. 10155 - 10172 (2018/11/23)
SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin subfamily A member 2 (SMARCA2), also known as Brahma homologue (BRM), is a Snf2-family DNA-dependent ATPase. BRM and its close homologue Brahma-related gene 1 (BRG1), also known as SMARCA4, are mutually exclusive ATPases of the large ATP-dependent SWI/SNF chromatin-remodeling complexes involved in transcriptional regulation of gene expression. No small molecules have been reported that modulate SWI/SNF chromatin-remodeling activity via inhibition of its ATPase activity, an important goal given the well-established dependence of BRG1-deficient cancers on BRM. Here, we describe allosteric dual BRM and BRG1 inhibitors that downregulate BRM-dependent gene expression and show antiproliferative activity in a BRG1-mutant-lung-tumor xenograft model upon oral administration. These compounds represent useful tools for understanding the functions of BRM in BRG1-loss-of-function settings and should enable probing the role of SWI/SNF functions more broadly in different cancer contexts and those of other diseases.
