38235-71-1Relevant articles and documents
Discovery of novel inhibitors of human phosphoglycerate dehydrogenase by activity-directed combinatorial chemical synthesis strategy
Gou, Kun,Luo, Youfu,Luo, Yuan,Sun, Qingxiang,Tan, Yuping,Tao, Lei,Zhao, Yinglan,Zhou, Xia,Zhou, Yue,Zuo, Zeping
, (2021/07/26)
Serine, the source of the one-carbon units essential for de novo purine and deoxythymidine synthesis plays a crucial role in the growth of cancer cells. Phosphoglycerate dehydrogenase (PHGDH) which catalyzes the first, rate-limiting step in de novo serine biosynthesis has become a promising target for the cancer treatment. Here we identified H-G6 as a potential PHGDH inhibitor from the screening of an in-house small molecule library based on the enzymatic assay. We adopted activity-directed combinatorial chemical synthesis strategy to optimize this hit compound. Compound b36 was found to be the noncompetitive and the most promising one with IC50 values of 5.96 ± 0.61 μM against PHGDH. Compound b36 inhibited the proliferation of human breast cancer and ovarian cancer cells, reduced intracellular serine synthesis, damaged DNA synthesis, and induced cell cycle arrest. Collectively, our results suggest that b36 is a novel PHGDH inhibitor, which could be a promising modulator to reprogram the serine synthesis pathway and might be a potential anticancer lead worth further exploration.
FUNCTIONALISED AND SUBSTITUTED CARBAZOLES AS ANTI-CANCER AGENTS
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Page/Page column 38, (2016/02/26)
The present invention relates to anti-tropomyosin compounds, processes for their preparation, and methods for treating or preventing a disease or disorder, such as a proliferative disease (preferably cancer), using compounds of the invention.
Methods and Compositions for Modulating P300/CBP Activity
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Page/Page column 19, (2010/09/05)
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.
Virtual ligand screening of the p300/CBP histone acetyltransferase: Identification of a selective small molecule inhibitor
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.
scheme or table, p. 471 - 482 (2011/08/06)
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.
