Pyrazole inhibitors of coactivator associated arginine methyltransferase 1 (CARM1)

Purandare, Ashok V.; Chen, Zhong; Huynh, Tram; Pang, Suhong; Geng, Jieping; Vaccaro, Wayne; Poss, Michael A.; O’Connell, Jonathan C.; Nowak, Kimberly; Jayaraman, Lata

doi:10.1016/j.bmcl.2008.06.026

Cited by 83 publications

(63 citation statements)

References 16 publications

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“…A random HTS hit and its subsequent synthetic optimization led to the identification of a potent selective inhibitor of CARM1 (compound 15; see Figure 4). [113] Inhibitors of histone demethylases…”

Section: Arginine Methyltransferase Inhibitorsmentioning

confidence: 99%

The Emerging Therapeutic Potential of Histone Methyltransferase and Demethylase Inhibitors

et al. 2009

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Epigenetics is defined as heritable changes to the transcriptome that are independent of changes in the genome. The biochemical modifications that govern epigenetics are DNA methylation and posttranslational histone modifications. Among the histone modifications, acetylation and deacetylation are well characterized, whereas the fields of histone methylation and especially demethylation are still in their infancy. This is particularly true with regard to drug discovery. There is strong evidence that these modifications play an important role in the maintenance of transcription as well as in the development of certain diseases. This article gives an overview of the mechanisms of action of histone methyltransferases and demethylases, their role in the formation of certain diseases, and available inhibitors. Special emphasis is placed on the strategies that led to the first inhibitors which are currently available and the screening approaches that were used in that process.

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Section: Arginine Methyltransferase Inhibitorsmentioning

confidence: 99%

The Emerging Therapeutic Potential of Histone Methyltransferase and Demethylase Inhibitors

et al. 2009

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“…MTA, a nucleoside inhibitor of methyltransferases, blocks the transfer of methyl groups from AdoMet to PRMT substrates. Recently, a large number of efforts are underway, both in academia and in pharma, to identify small molecule inhibitors that selectively inhibit specific PRMTs (Cheng et al, 2004;Purandare et al, 2008;Spannhoff et al, 2007). Although a number of specific PRMT inhibitors have been identified using in vitro screens, these compounds have proven to be of limited use due to their inability to enter cells or their cytotoxic effects.…”

Section: Using Global-methylation Inhibitorsmentioning

confidence: 99%

Methods Applied to the Study of Protein Arginine Methylation

Cheng

Vemulapalli

Bedford

2012

Methods in Enzymology

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“…The MLL (mixed lineage leukemia) protein is a SET domain TrxG H3K4 methyltransferase and is essential for both embryonic development and normal hematopoiesis through regulation of Hox genes and other target genes important for developmental regulation (148,149). The importance of these enzymes in disease and the fact that they appear to be amenable to inhibition by small molecules have spurred their analysis in structural genomics projects (150)(151)(152).…”

Section: Histone Methyltransferasesmentioning

confidence: 99%

Large-Scale Structural Biology of the Human Proteome

Edwards

2009

Annu. Rev. Biochem.

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The large-scale structural biology projects that target human proteins focus predominantly on the catalytic domains of potential therapeutic targets and the domains of human proteins that mediate protein-protein and protein-small-molecule interactions. Their main scientific objective is to elucidate the molecular basis for specificity and selectivity of function within large protein families of therapeutic interest, such as kinases, phosphatases, and proteins involved in epigenetic regulation. Half of the unique human protein structures determined in the past three years derive from these initiatives.

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Pyrazole inhibitors of coactivator associated arginine methyltransferase 1 (CARM1)

Cited by 83 publications

References 16 publications

The Emerging Therapeutic Potential of Histone Methyltransferase and Demethylase Inhibitors

The Emerging Therapeutic Potential of Histone Methyltransferase and Demethylase Inhibitors

Methods Applied to the Study of Protein Arginine Methylation

Large-Scale Structural Biology of the Human Proteome

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