Discovery of novel potent migrastatic Thiazolo[5,4-b]pyridines targeting Lysyl-tRNA synthetase (KRS) for treatment of Cancer metastasis

Lee, Seungbeom; Kwon, Nam Hoon; Seo, Bokyung; Lee, Jin Young; Cho, Hye Young; Kim, Kyeojin; Kim, Hyun Su; Jung, Kiwon; Jeon, Young Ho; Kim, Sung‐Hoon; Suh, Young-Ger

doi:10.1016/j.ejmech.2021.113405

Cited by 11 publications

(6 citation statements)

References 22 publications

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“…Similarly, BC-LI-0186 prevents LARS1 lysosomal localization and mTORC1 activation by blocking RagD-LARS1 interaction [51] . Small molecule inhibitors against KARS1, e.g., SL-1910, reduce migration of MDA-MB-231 cells, whereas BC-K_YH16899 inhibits the interaction of KARS1 and 67 kDa laminin receptor, thereby suppressing membrane localization in cells and metastasis in mouse models [ 210 , 211 ]. Inhibition of caspase-8-mediated cleavage of KARS1 abrogates its secretion via exosomes and reduces inflammation [69] .…”

Section: Aarss and Immune Regulation: A Potential Link To Cancer Deve...mentioning

confidence: 99%

“…Inhibition of caspase-8-mediated cleavage of KARS1 abrogates its secretion via exosomes and reduces inflammation [69] . Thiazolo[5,4- b ]pyridines (SL-1910) is a KARS1 inhibitor that reduces cell migration and prevents tumor metastasis in mice [210] . L -canavanine is a structural analog of L -arginine that as an RARS1 substrate is competitively incorporated into nascent proteins.…”

Section: Aarss and Immune Regulation: A Potential Link To Cancer Deve...mentioning

confidence: 99%

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Aminoacyl-tRNA synthetases of the multi-tRNA synthetase complex and their role in tumorigenesis

Khan

Fox

2022

Translational Oncology

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Section: Aarss and Immune Regulation: A Potential Link To Cancer Deve...mentioning

confidence: 99%

Section: Aarss and Immune Regulation: A Potential Link To Cancer Deve...mentioning

confidence: 99%

Aminoacyl-tRNA synthetases of the multi-tRNA synthetase complex and their role in tumorigenesis

Khan

Fox

2022

Translational Oncology

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“…For example, the KRS inhibitor BC-K-YH16899, binds to KRS and blocks the interaction between KRS and 67LR without affecting the catalytic activity of KRS, and has been validated to have an anti-metastatic effect in mouse model of lung cancer ( Kim D. G. et al, 2014 ). Another inhibitor SL-1910, was also reported to inhibit the migration of breast cancer cells ( Lee et al, 2021 ). Another mechanism could also explain KRS mediated cell migration.…”

Section: Aminoacyl-trna Synthetases and Cancermentioning

confidence: 99%

The pathophyiological role of aminoacyl-tRNA synthetases in digestive system diseases

et al. 2022

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Aminoacyl-tRNA synthetases (ARSs) catalyze the ligation of amino acids to their cognate transfer RNAs and are indispensable enzymes for protein biosynthesis in all the cells. Previously, ARSs were considered simply as housekeeping enzymes, however, they are now known to be involved in a variety of physiological and pathological processes, such as tumorigenesis, angiogenesis, and immune response. In this review, we summarize the role of ARSs in the digestive system, including the esophagus, stomach, small intestine, colon, as well as the auxiliary organs such as the pancreas, liver, and the gallbladder. Furthermore, we specifically focus on the diagnostic and prognostic value of ARSs in cancers, aiming to provide new insights into the pathophysiological implications of ARSs in tumorigenesis.

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“…Nitrogen-, oxygen- and sulfur-based heterocyclic compounds are contributing extensively in the current medicinal chemistry because of their wide applications in drug discovery and development [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 ]. As the potentially privileged scaffolds, pyridine-fused heterocycles have attracted attention due to their effective and widespread biological properties for the treatment of different diseases such as cancer, diabetes, hyperpigmentation, tuberculosis, hyperplasia and ulcer [ 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

Pyridine Scaffolds, Phenols and Derivatives of Azo Moiety: Current Therapeutic Perspectives

et al. 2021

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Synthetic heterocyclic compounds have incredible potential against different diseases; pyridines, phenolic compounds and the derivatives of azo moiety have shown excellent antimicrobial, antiviral, antidiabetic, anti-melanogenic, anti-ulcer, anticancer, anti-mycobacterial, anti-inflammatory, DNA binding and chemosensing activities. In the present review, the above-mentioned activities of the nitrogen-containing heterocyclic compounds (pyridines), hydroxyl (phenols) and azo derivatives are discussed with reference to the minimum inhibitory concentration and structure–activity relationship, which clearly indicate that the presence of nitrogen in the phenyl ring; in addition, the hydroxyl substituent and the incorporation of a diazo group is crucial for the improved efficacies of the compounds in probing different diseases. The comparison was made with the reported drugs and new synthetic derivatives that showed recent therapeutic perspectives made in the last five years.

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Discovery of novel potent migrastatic Thiazolo[5,4-b]pyridines targeting Lysyl-tRNA synthetase (KRS) for treatment of Cancer metastasis

Cited by 11 publications

References 22 publications

Aminoacyl-tRNA synthetases of the multi-tRNA synthetase complex and their role in tumorigenesis

Aminoacyl-tRNA synthetases of the multi-tRNA synthetase complex and their role in tumorigenesis

The pathophyiological role of aminoacyl-tRNA synthetases in digestive system diseases

Pyridine Scaffolds, Phenols and Derivatives of Azo Moiety: Current Therapeutic Perspectives

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