The Discovery of Aurora Kinase Inhibitor by  Multi-Docking-Based Virtual Screening

Kim, Jun-Tae; Jung, Seo Hee; Kang, Suna; Ryu, Chong Kul; Kang, Nam Sook

doi:10.3390/ijms151120403

Cited by 3 publications

(1 citation statement)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…(C) Afterwards, 67 compounds that exhibited concentration-dependent binding to NLP Pya were further screened at an extended range of concentrations. The titrations shown are for the compound 5D11 [61], which was titrated with concentrations ranging from 31 to 500 μM (from the bottom to the top in the upper graph). 5D11 does not exhibit saturated binding for the tested concentration range (bottom graph).…”

Section: The Selected Compounds Inhibited Nlp-induced Necrosismentioning

confidence: 99%

Nep1-like proteins as a target for plant pathogen control

et al. 2021

View full text Add to dashboard Cite

The lack of efficient methods to control the major diseases of crops most important to agriculture leads to huge economic losses and seriously threatens global food security. Many of the most important microbial plant pathogens, including bacteria, fungi, and oomycetes, secrete necrosis- and ethylene-inducing peptide 1 (Nep1)-like proteins (NLPs), which critically contribute to the virulence and spread of the disease. NLPs are cytotoxic to eudicot plants, as they disturb the plant plasma membrane by binding to specific plant membrane sphingolipid receptors. Their pivotal role in plant infection and broad taxonomic distribution makes NLPs a promising target for the development of novel phytopharmaceutical compounds. To identify compounds that bind to NLPs from the oomycetes Pythium aphanidermatum and Phytophthora parasitica, a library of 587 small molecules, most of which are commercially unavailable, was screened by surface plasmon resonance. Importantly, compounds that exhibited the highest affinity to NLPs were also found to inhibit NLP-mediated necrosis in tobacco leaves and Phytophthora infestans growth on potato leaves. Saturation transfer difference-nuclear magnetic resonance and molecular modelling of the most promising compound, anthranilic acid derivative, confirmed stable binding to the NLP protein, which resulted in decreased necrotic activity and reduced ion leakage from tobacco leaves. We, therefore, confirmed that NLPs are an appealing target for the development of novel phytopharmaceutical agents and strategies, which aim to directly interfere with the function of these major microbial virulence factors. The compounds identified in this study represent lead structures for further optimization and antimicrobial product development.

show abstract

Section: The Selected Compounds Inhibited Nlp-induced Necrosismentioning

confidence: 99%

Nep1-like proteins as a target for plant pathogen control

et al. 2021

View full text Add to dashboard Cite

show abstract

The two sides of chromosomal instability: drivers and brakes in cancer

Hosea,

Hillary,

Naqvi

et al. 2024

Sig Transduct Target Ther

View full text Add to dashboard Cite

Chromosomal instability (CIN) is a hallmark of cancer and is associated with tumor cell malignancy. CIN triggers a chain reaction in cells leading to chromosomal abnormalities, including deviations from the normal chromosome number or structural changes in chromosomes. CIN arises from errors in DNA replication and chromosome segregation during cell division, leading to the formation of cells with abnormal number and/or structure of chromosomes. Errors in DNA replication result from abnormal replication licensing as well as replication stress, such as double-strand breaks and stalled replication forks; meanwhile, errors in chromosome segregation stem from defects in chromosome segregation machinery, including centrosome amplification, erroneous microtubule–kinetochore attachments, spindle assembly checkpoint, or defective sister chromatids cohesion. In normal cells, CIN is deleterious and is associated with DNA damage, proteotoxic stress, metabolic alteration, cell cycle arrest, and senescence. Paradoxically, despite these negative consequences, CIN is one of the hallmarks of cancer found in over 90% of solid tumors and in blood cancers. Furthermore, CIN could endow tumors with enhanced adaptation capabilities due to increased intratumor heterogeneity, thereby facilitating adaptive resistance to therapies; however, excessive CIN could induce tumor cells death, leading to the “just-right” model for CIN in tumors. Elucidating the complex nature of CIN is crucial for understanding the dynamics of tumorigenesis and for developing effective anti-tumor treatments. This review provides an overview of causes and consequences of CIN, as well as the paradox of CIN, a phenomenon that continues to perplex researchers. Finally, this review explores the potential of CIN-based anti-tumor therapy.

show abstract

The hunt for antimitotic agents: an overview of structure-based design strategies

Dube

Tiwari

Kaur

2016

Expert Opinion on Drug Discovery

View full text Add to dashboard Cite

The advent of structure-based drug design coupled with advances in X-ray crystallography has revolutionized the discovery of candidate lead molecules. The structural insights gleaned from the co-complex protein-drug interactions have provided a new dimension in the design of anti-mitotic molecules to develop drugs with a higher selectivity and specificity profile. Targeting non-catalytic domains has provided an alternate approach to address cross-reactivity and broad selectivity among kinase inhibitors. The elucidation of structures of emerging mitotic drug targets has opened avenues for the design of inhibitors that target cancer.

show abstract

The Discovery of Aurora Kinase Inhibitor by Multi-Docking-Based Virtual Screening

Cited by 3 publications

References 25 publications

Nep1-like proteins as a target for plant pathogen control

Nep1-like proteins as a target for plant pathogen control

The two sides of chromosomal instability: drivers and brakes in cancer

The hunt for antimitotic agents: an overview of structure-based design strategies

Contact Info

Product

Resources

About