Histone Methyltransferase Inhibitors for Cancer Therapy

Li, Keqin Kathy; Huang, Kenneth; Kondengaden, Shukkoor Muhammed; Wooten, Jonathan; Reyhanfard, Hamed; Zhang, Qing; Zhai, Bingxue Chris; Wang, Peng George

doi:10.1016/b978-0-12-801080-8.00017-x

Cited by 2 publications

(2 citation statements)

References 101 publications

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“…There are over 20 hDOT1L small molecule inhibitors and can be categorized into four groups based on their mode of action: (i) SAH(S-adenosyl-L-homocysteine)mimicking compounds; (ii) benzimidazole or (iii) urea group-containing compounds; and (iv) carbamate-containing compounds [143]. The activity of human homolog of yeast DOT1L or hDOT1L is mostly dysregulated in a subset of acute myeloid leukemia that has MLL gene translocation.…”

Section: Small Molecule Inhibitors Of Hdot1lmentioning

confidence: 99%

Discovery of Small Molecule Inhibitors for Histone Methyltransferases in Cancer

Motolani¹,

Sun²,

Martin³

et al. 2021

Translational Research in Cancer

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Cancer is the second leading cause of mortality in the United States. There are several therapeutic regimens employed to mitigate the mortality rate of cancer. This includes the use of chemotherapy, radiation, immunotherapy, and precision medicine/targeted therapy. Targeted therapy involves the use of drugs that target a specific pathway or biomolecule compromised in cancer for cancer treatment. Aberrant expression of epigenetic enzymes has been well documented for their contribution in driving tumorigenesis and other cancer hallmarks. Hence, there is an urgent need for novel drug discovery and development in epigenetics to help combat various cancer morbidities. Herein, we review the roles and consequences of dysregulated function of several epigenetic enzymes, with a focus on histone methyltransferases (HMTs). Additionally, we discussed the current efforts made in the development of small molecule inhibitors for a few representative HMTs implicated in different cancers. Furthermore, the common screening assays used in discovering potent small molecule inhibitors were also detailed in this chapter. Overall, this book chapter highlights the significance of targeting HMTs in different cancers and the clinical application potentials/limitations faced by the developed or emerging small molecule inhibitors of HMTs for the purpose of cancer therapy.

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Section: Small Molecule Inhibitors Of Hdot1lmentioning

confidence: 99%

Discovery of Small Molecule Inhibitors for Histone Methyltransferases in Cancer

Motolani¹,

Sun²,

Martin³

et al. 2021

Translational Research in Cancer

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“…The development of innovative personalized therapies based on the use of DOT1L inhibitors for the treatment of pediatric and adult MLLr has shown encouraging results 55 . DOT1L catalyzes the mono-, di-, and tri-methylation of H3K79 within the ordered core of H3 and is required to initiate tumorigenesis and maintain the malignant phenotype of MLLr 56 . Thus, DOT1L inhibitors hold considerable promise in the clinical management of leukemia.…”

Section: Covalent Histone Modificationsmentioning

confidence: 99%

Genetics and epigenetics of pediatric leukemia in the era of precision medicine

Ramos

Zeng

et al. 2018

F1000Res

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Pediatric leukemia represents a heterogeneous group of diseases characterized by germline and somatic mutations that manifest within the context of disturbances in the epigenetic machinery and genetic regulation. Advances in genomic medicine have allowed finer resolution of genetic and epigenetic strategies that can be effectively used to risk-stratify patients and identify novel targets for therapy. This review discusses the genetic and epigenetic mechanisms of leukemogenesis, particularly as it relates to acute lymphocytic leukemias, the mechanisms of epigenetic control of leukemogenesis, namely DNA methylation, histone modifications, microRNAs, and LINE-1 retroelements, and highlights opportunities for precision medicine therapeutics in further guiding disease management. Future efforts to broaden the integration of advances in genomic and epigenomic science into the practice of pediatric oncology will not only identify novel therapeutic strategies to improve clinical outcomes but also improve the quality of life for this unique patient population. Recent findings in precision therapeutics of acute lymphocytic leukemias over the past three years, along with some provocative areas of epigenetics research, are reviewed here.

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Histone Methyltransferase Inhibitors for Cancer Therapy

Cited by 2 publications

References 101 publications

Discovery of Small Molecule Inhibitors for Histone Methyltransferases in Cancer

Discovery of Small Molecule Inhibitors for Histone Methyltransferases in Cancer

Genetics and epigenetics of pediatric leukemia in the era of precision medicine

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