- Histone acetyltransferase P300 small molecule inhibitor and medicinal composition and application thereof
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The compound capable of inhibiting histone acetyltransferase, has a significant inhibition effect p300 in inhibiting the activity, of the histone acetyltransferase, or a pharmaceutically acceptable salt (I) of; has a significant inhibitory effect on tumor cells such as the primary, representative small molecule inhibitor p300 to prostate cancer cells, malignant blood tumor cells p300 breast cancer cells, and has an effect of inhibiting the toxicity C646, of the compound by overcoming the defects, of the original, small molecule inhibitor, existing in the present invention. C646 p300. The compounds of the formula C646; are shown in, Table (I). The invention belongs to, the field of pharmaceutical chemistry.
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- Development of novel alkene oxindole derivatives as orally efficacious AMP-activated protein kinase activators
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Adenosine 5′-monophosphate-activated protein kinase (AMPK) is emerging as a promising drug target for its regulatory function in both glucose and lipid metabolism. Compound PT1 (5) was originally identified from high throughput screening as a small molecu
- Yu, Li-Fang,Li, Yuan-Yuan,Su, Ming-Bo,Zhang, Mei,Zhang, Wei,Zhang, Li-Na,Pang, Tao,Zhang, Run-Tao,Liu, Bing,Li, Jing-Ya,Li, Jia,Nan, Fa-Jun
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supporting information
p. 475 - 480
(2013/07/25)
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- Virtual ligand screening of the p300/CBP histone acetyltransferase: Identification of a selective small molecule inhibitor
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The histone acetyltransferase (HAT) p300/CBP is a transcriptional coactivator implicated in many gene regulatory pathways and protein acetylation events. Although p300 inhibitors have been reported, a potent, selective, and readily available active-sitedirected small molecule inhibitor is not yet known. Here we use a structure-based, in silico screening approach to identify a commercially available pyrazolone- containing small molecule p300 HAT inhibitor, C646. C646 is a competitive p300 inhibitor with a Ki of 400 nM and is selective versus other acetyltransferases. Studies on site-directed p300 HAT mutants and synthetic modifications of C646 confirm the importance of predicted interactions in conferring potency. Inhibition of histone acetylation and cell growth by C646 in cells validate its utility as a pharmacologic probe and suggest that p300/CBP HAT is a worthy anticancer target.
- Bowers, Erin M.,Yan, Gai,Mukherjee, Chandrani,Orry, Andrew,Wang, Ling,Holbert, Marc A.,Crump, Nicholas T.,Hazzalin, Catherine A.,Liszczak, Glen,Yuan, Hua,Larocca, Cecilia,Saldanha, S. Adrian,Abagyan, Ruben,Sun, Yan,Meyers, David J.,Marmorstein, Ronen,Mahadevan, Louis C.,Alani, Rhoda M.,Cole, Philip A.
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scheme or table
p. 471 - 482
(2011/08/06)
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- Methods and Compositions for Modulating P300/CBP Activity
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The present invention relates to a method for identifying compounds that modulate the activity of p300/CBP. Compounds of the invention are identified by designing or screening for a compound which binds to at least one amino acid residue of the newly identified lysine-CoA inhibitor binding site, L1 loop, electronegative pocket, or electronegative groove of the HAT domain of p300/CBP and testing the compound for its ability to modulate the activity of p300/CBP. Compositions and methods for preventing or treating diseases or disorders associated with p300/CBP are also provided as is a method for producing a semi-synthetic HAT domain.
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Page/Page column 20
(2010/09/05)
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