Identifying potential selective fluorescent probes for cancer-associated protein carbonic anhydrase IX using a computational approach

Kamstra, Rhiannon; Floriano, Wely B.

doi:10.1016/j.jmgm.2014.10.010

Cited by 2 publications

(1 citation statement)

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“…The validation, screening and analog libraries were screened against the target structure using HierVLS, a hierarchical virtual screening protocol described in details elsewhere . This protocol reports force‐field‐based (FF) binding energies that take solvation into account for the best‐scoring protein–ligand complex generated for each ligand in the screening database.…”

Section: Methodsmentioning

confidence: 99%

N‐(2,4)‐dinitrophenyl‐L‐arginine Interacts with EphB4 and Functions as an EphB4 Kinase Modulator

2015

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The erythropoietin-producing hepatocellular carcinoma receptor B4 is a receptor tyrosine kinase whose expression is preserved in various malignancies, including colon, gastric, and breast carcinoma. Hepatocellular carcinoma receptor B4 presence in tumor cells and involvement in cancer suppression makes it a potential therapeutic target for activating compounds. Moreover, modulators of its activity also have a strong potential to be used in diagnosis and therapy monitoring. We used virtual ligand screening to identify novel hepatocellular carcinoma receptor B4 kinase modulators for experimental testing. Three independent assay platforms confirmed that dinitrophenyl-L-arginine is likely to affect the kinase activity of hepatocellular carcinoma receptor B4. An enzyme-coupled spectrophotometric assay has been used to examine this possibility and may prove to be useful for assessing other novel kinase modulator candidates. Overall, our observations suggest that dinitrophenyl-L-arginine has an activating effect on hepatocellular carcinoma receptor B4 and, therefore, more efficient derivatives may have therapeutic effects in tumors where hepatocellular carcinoma receptor B4 exhibits antimalignant properties. The hepatocellular carcinoma receptor B4-activating effect is discussed with respect to previously described mechanisms, using predicted and experimental structures for docked ligands. As a novel kinase activity modulator, dinitrophenyl-L-arginine may provide new insights into molecular mechanisms by which kinases are activated or regulated, and may serve as a lead compound for the generation of novel hepatocellular carcinoma receptor B4-activating therapeutic compounds.

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Section: Methodsmentioning

confidence: 99%