Advances in targeting 'undruggable'transcription factors with small molecules

MJ Henley, AN Koehler - Nature Reviews Drug Discovery, 2021‏ - nature.com
Transcription factors (TFs) represent key biological players in diseases including cancer,
autoimmunity, diabetes and cardiovascular disease. However, outside nuclear receptors …

Targeting arginine methyltransferase PRMT5 for cancer therapy: updated progress and novel strategies

J Zheng, B Li, Y Wu, X Wu, Y Wang - Journal of Medicinal …, 2023‏ - ACS Publications
As a predominant type II protein arginine methyltransferase, PRMT5 plays critical roles in
various normal cellular processes by catalyzing the mono-and symmetrical dimethylation of …

[HTML][HTML] Small molecules targeting protein–protein interactions for cancer therapy

D Wu, Y Li, L Zheng, H **ao, L Ouyang, G Wang… - … Pharmaceutica Sinica B, 2023‏ - Elsevier
Protein–protein interactions (PPIs) are fundamental to many biological processes that play
an important role in the occurrence and development of a variety of diseases. Targeting the …

Structure, function and inhibition of critical protein–protein interactions involving mixed lineage leukemia 1 and its fusion oncoproteins

X Li, Y Song - Journal of hematology & oncology, 2021‏ - Springer
Abstract Mixed lineage leukemia 1 (MLL1, also known as MLL or KMT2A) is an important
transcription factor and histone-H3 lysine-4 (H3K4) methyltransferase. It is a master …

Approaching the catalytic mechanism of protein lysine methyltransferases by biochemical and simulation techniques

P Schnee, J Pleiss, A Jeltsch - Critical Reviews in Biochemistry and …, 2024‏ - Taylor & Francis
Protein lysine methyltransferases (PKMTs) transfer up to three methyl groups to the side
chains of lysine residues in proteins and fulfill important regulatory functions by controlling …

Small Molecule Menin Inhibitors: Novel Therapeutic Agents Targeting Acute Myeloid Leukemia with KMT2A Rearrangement or NPM1 Mutation

X Thomas - Oncology and Therapy, 2024‏ - Springer
Recent advances have included insights into the clinical value of genomic abnormalities in
acute myeloid leukemia (AML) and consequently the development of numerous targeted …

Discovery of a new-generation S-Adenosylmethionine-noncompetitive covalent inhibitor targeting the lysine methyltransferase enhancer of zeste homologue 2

Y Zhang, H Yang, B Li, J Li, H Li, Q Shi… - Journal of Medicinal …, 2023‏ - ACS Publications
The first-generation enhancer of zeste homologue 2 (EZH2) inhibitors suffer from several
limitations, such as high dosage, cofactor S-adenosylmethionine (SAM) competition, and …

Menin–MLL1 interaction small molecule inhibitors: A potential therapeutic strategy for leukemia and cancers

Q Shi, M Xu, Z Kang, M Zhang, Y Luo - Molecules, 2023‏ - mdpi.com
Encoded by the MEN1 gene, menin protein is a fusion protein that is essential for the
oncogenic transformation of mixed-lineage leukemia (MLL) and leads to acute leukemia …

Chemical biology and pharmacology of histone lysine methylation inhibitors

SH Barghout, RAC Machado… - Biochimica et Biophysica …, 2022‏ - Elsevier
Histone lysine methylation is a post-translational modification that plays a key role in the
epigenetic regulation of a broad spectrum of biological processes. Moreover, the …

Menin-MLL protein-protein interaction inhibitors: a patent review (2014–2021)

H Bai, SQ Zhang, H Lei, F Wang, M Ma… - Expert Opinion on …, 2022‏ - Taylor & Francis
Introduction Chromosomal translocations involving the mixed-lineage leukemia (MLL,
KMT2A, MLL1) genes result in the production of MLL fusion proteins, which cause abnormal …