406233-26-9Relevant articles and documents
Molecular dynamics study-guided identification of cyclic amine structures as novel hydrophobic tail components of hPPARγ agonists
Tanaka, Yuta,Gamo, Kanae,Oyama, Takuji,Ohashi, Masao,Waki, Minoru,Matsuno, Kenji,Matsuura, Nobuyasu,Tokiwa, Hiroaki,Miyachi, Hiroyuki
, p. 4001 - 4005 (2014/09/17)
We previously reported that a α-benzylphenylpropanoic acid-type hPPARγ-selective agonist with a piperidine ring as the hydrophobic tail part (3) exhibited sub-micromolar-order hPPARγ agonistic activity. In order to enhance the activity, we planned to carr
Discovery and structure-activity relationship of antagonists of B-cell lymphoma 2 family proteins with chemopotentiation activity in vitro and in vivo
Wendt, Michael D.,Shen, Wang,Kunzer, Aaron,McClellan, William J.,Bruncko, Milan,Oost, Thorsten K.,Ding, Hong,Joseph, Mary K.,Zhang, Haichao,Nimmer, Paul M.,Ng, Shi-Chung,Shoemaker, Alexander R.,Petros, Andrew M.,Oleksijew, Anatol,Marsh, Kennan,Bauch, Joy,Oltersdorf, Tilman,Belli, Barbara A.,Martineau, Darlene,Fesik, Stephen W.,Rosenberg, Saul H.,Elmore, Steven W.
, p. 1165 - 1181 (2007/10/03)
Development of a rationally designed potentiator of cancer chemotherapy, via inhibition of Bcl-XL function, is described. Lead compounds generated by NMR screening and directed parallel synthesis displayed sub-μM binding but were strongly deactivated in the presence of serum. The dominant component of serum deactivation was identified as domain III of human serum albumin (HSA); NMR solution structures of inhibitors bound to both Bcl-X L and HSA domain III indicated two potential optimization sites for separation of affinities. Modifications at both sites resulted in compounds with improved Bcl-XL binding and greatly increased activity in the presence of human serum, culminating in 73R, which bound to Bcl-XL with a Ki of 0.8 μM. In a cellular assay 73R reversed the protection afforded by Bcl-XL overexpression against cytokine deprivation in FL5.12 cells with an EC50 of 0.47 μM. 73R showed little effect on the viability of the human non small cell lung cancer cell line A549. However, consistent with the proposed mechanism, 73R potentiated the activity of paclitaxel and UV irradiation in vitro and potentiated the antitumor efficacy of paclitaxel in a mouse xenograft model.
N-sulfonylcarboximidamide apoptosis promoters
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Page/Page column 12, (2008/06/13)
Compounds having the formula are apoptosis promoters. Also disclosed are methods of making the compounds, compositions containing the compounds, and methods of treatment using the compounds.
N-acylsulfonamide apoptosis promoters
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, (2008/06/13)
N-Benzoyl arylsulfonamides having the formula are BCL-Xl inhibitors and are useful for promoting apoptosis. Also disclosed are BCL-Xl inhibiting compositions and methods of promoting apoptosis in a mammal.
N-Acylsulfonamide apoptosis promoters
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, (2008/06/13)
N-Benzoyl arylsulfonamides having the formula Are BCL-X1 inhibitors and are useful for promoting apoptosis. Also disclosed are BCL-X1 inhibiting compositions and methods of promoting apoptosis in a mammal.