The First Structure of Human MTHFD2L and Its Implications for the Development of Isoform‐Selective Inhibitors
Sign Up to like & getrecommendations! Published in 2022 at "Chemmedchem"
DOI: 10.1002/cmdc.202200274
Abstract: Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) is a mitochondrial 1‐carbon metabolism enzyme, which is an attractive anticancer drug target as it is highly upregulated in cancer but is not expressed in healthy adult cells. Selective MTHFD2 inhibitors… read more here.
Keywords: mthfd2l; isoform selective; structure; structure human ... See more keywords
Discovery of Potent and Isoform‐selective Histone Deacetylase Inhibitors Using Structure‐based Virtual Screening and Biological Evaluation
Sign Up to like & getrecommendations! Published in 2022 at "Molecular Informatics"
DOI: 10.1002/minf.202100295
Abstract: Histone deacetylases (HDACs) are key enzymes in epigenetics and promising targets for anticancer therapy. Although several drugs targeting HDAC have been approved for the treatment of tumors, their clinical use has been limited by their… read more here.
Keywords: evaluation; isoform selective; histone; discovery potent ... See more keywords
Structure-Based Development of Isoform-Selective Inhibitors of Casein Kinase 1ε vs Casein Kinase 1δ.
Sign Up to like & getrecommendations! Published in 2023 at "Journal of medicinal chemistry"
DOI: 10.1021/acs.jmedchem.2c01180
Abstract: Specific inhibition of a single kinase isoform is a challenging task due to the highly conserved nature of ATP-binding sites. Casein kinase 1 (CK1) δ and ε share 97% sequence identity in their catalytic domains.… read more here.
Keywords: isoform selective; casein kinase; ck1; structure ... See more keywords
Discovery of Novel Indazole Chemotypes as Isoform-Selective JNK3 Inhibitors for the Treatment of Parkinson's Disease.
Sign Up to like & getrecommendations! Published in 2023 at "Journal of medicinal chemistry"
DOI: 10.1021/acs.jmedchem.2c01410
Abstract: c-Jun N-terminal kinases (JNKs) are involved in the pathogenesis of various diseases. In particular, JNK3 and not JNK1/2 is primarily expressed in the brain and plays a key role in mediating neurodegenerative diseases like Parkinson's… read more here.
Keywords: isoform selective; jnk3; parkinson disease; jnk3 inhibitors ... See more keywords
Thiophene-Pyrazolourea Derivatives as Potent, Orally Bioavailable, and Isoform-Selective JNK3 Inhibitors
Sign Up to like & getrecommendations! Published in 2021 at "ACS Medicinal Chemistry Letters"
DOI: 10.1021/acsmedchemlett.0c00533
Abstract: Potent JNK3 isoform selective inhibitors were developed from a thiophenyl-pyrazolourea scaffold. Through structure activity relationship (SAR) studies utilizing enzymatic and cell-based assays, and in vitro and in vivo drug metabolism and pharmacokinetic (DMPK) studies, potent… read more here.
Keywords: orally bioavailable; jnk3 inhibitors; selective jnk3; jnk3 ... See more keywords
Isoform-selective regulation of mammalian cryptochromes
Sign Up to like & getrecommendations! Published in 2020 at "Nature Chemical Biology"
DOI: 10.1038/s41589-020-0505-1
Abstract: CRY1 and CRY2 are essential components of the circadian clock controlling daily physiological rhythms. Accumulating evidences indicate distinct roles of these highly homologous proteins, in addition to redundant functions. Therefore, the development of isoform-selective compounds… read more here.
Keywords: compound; isoform selective; cry1 cry2; clock ... See more keywords
A computational prospective on isoform-selective CB2 inhibitors
Sign Up to like & getrecommendations! Published in 2021 at "New Journal of Chemistry"
DOI: 10.1039/d1nj02296b
Abstract: The strategy of enlarging the molecular size, increasing hydrogen bond interactions with the key residues of CB2, and furthering geometric distribution of hydrophobic groups would improve the selectivity towards CB2 receptor. read more here.
Keywords: prospective isoform; computational prospective; isoform selective; chemistry ... See more keywords
Isoform-selective HDAC1/6/8 inhibitors with an imidazo-ketopiperazine cap containing stereochemical diversity
Sign Up to like & getrecommendations! Published in 2018 at "Philosophical Transactions of the Royal Society B: Biological Sciences"
DOI: 10.1098/rstb.2017.0364
Abstract: A series of hydroxamic acids linked by different lengths to a chiral imidazo-ketopiperazine scaffold were synthesized. The compounds with linker lengths of 6 and 7 carbon atoms were the most potent in histone deacetylase (HDAC)… read more here.
Keywords: inhibitors imidazo; selective hdac1; imidazo ketopiperazine; hdac1 inhibitors ... See more keywords
Improving the Armamentarium of PI3K Inhibitors with Isoform-Selective Agents: A New Light in the Darkness.
Sign Up to like & getrecommendations! Published in 2017 at "Cancer discovery"
DOI: 10.1158/2159-8290.cd-17-0500
Abstract: Excitement and drug-development efforts aimed at targetable genetic aberrations in the PI3K/AKT/mTOR pathway have declined due to the limited clinical performance of these inhibitors as monotherapies. New, more isoform-selective treatments, such as taselisib, promise to… read more here.
Keywords: inhibitors isoform; armamentarium pi3k; improving armamentarium; isoform selective ... See more keywords