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Homozygous MTAP deletion occurs in ~15% of cancers, making them vulnerable to decreases in the concentration of S-adenosylmethionine (SAM). AG-270/S095033 is an oral, potent, reversible inhibitor of methionine adenosyltransferase 2 A (MAT2A), the enzyme primarily responsible for the synthesis of SAM. We report results from the first-in-human, phase 1 trial of AG-270/S095033 as monotherapy in patients with advanced malignancies (ClinicalTrials.

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N6-methyladenosine is one of the most common and reversible post-transcriptional modifications in eukaryotes, and it is involved in alternative splicing and RNA transcription, degradation, and translation. It is well known that cancer cells acquire energy through metabolic reprogramming to exhibit various biological behaviors. Moreover, numerous studies have demonstrated that m6A induces cancer metabolic reprogramming by regulating the expression of core metabolic genes or by activating metabolic signaling pathways.

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The cell-free supernatant of (LCFS) is considered a potential natural antimicrobial agent due to its outstanding antimicrobial activity. This study demonstrated that the cell-free supernatant of SHY96 (LCFS96) effectively inhibits the growth and biofilm formation of CMCC(B)54002 (_02) by reducing cell metabolic activity and damaging cell structure. Metabolomic analysis revealed that LCFS96 significantly altered 450 intracellular metabolites, affecting key metabolic pathways including linoleic acid metabolism, pyrimidine metabolism, purine metabolism, pantothenic acid and CoA biosynthesis, and the TCA cycle.

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Correction of aberrant splicing of ELP1 pre-mRNA by kinetin derivatives - A structure activity relationship study.

Eur J Med Chem

December 2024

Laboratory of Experimental Biology, Faculty of Science, Palacký University, Šlechtitelů 27, CZ-78371 Olomouc, Czech Republic; Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacký University, Hněvotínská 3, 775 15 Olomouc, Czech Republic. Electronic address:

Familial dysautonomia is a debilitating congenital neurodegenerative disorder with no causative therapy. It is caused by a homozygous mutation in ELP1 gene, resulting in the production of the transcript lacking exon 20. The compounds studied as potential treatments include the clinical candidate kinetin, a plant hormone from the cytokinin family.

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D-ribose-5-phosphate inactivates YAP and functions as a metabolic checkpoint.

J Hematol Oncol

January 2025

Department of Radiation Oncology, Henan Provincial Key Laboratory of Radiation Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, People's Republic of China.

Background: Targeting glucose uptake by glucose transporter (GLUT) inhibitors is a therapeutic opportunity, but efforts on GLUT inhibitors have not been successful in the clinic and the underlying mechanism remains unclear. We aim to identify the key metabolic changes responsible for cancer cell survival from glucose limitation and elucidate its mechanism.

Methods: The level of phosphorylated YAP was analyzed with Western blotting and Phos-tag immunoblotting.

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