Three-Pronged Approach to Curb Cancer Metastasis

BACKGROUND & OBJECTIVE: Extracellular signal-regulated kinases 1 and 2 [ERK1/2] have been reported to promote cancer spread through receptor tyrosine kinase (RTK)/Ras/Raf/MEK/ERK1/2 pathway hyperactivation. The extracellular ERK5 has also linked cancer. However, inhibition of ERK1/2 cause compensatory hyperactivation the pathway. Therefore, there is a need for simultaneous this trio by common inhibitor. This study aimed find novel inhibitor ERK1, ERK2 ERK5, with special focus on phytochemicals.
 METHODOLOGY: All available co-crystallized inhibitors MEK1, were used as references 2D search across zillions compounds. One hundred molecules best matching pharmacophores extracted per virtual chemical space. A total 20,000 new structurally diverse entities scaffold hopping ability sifted out from these spaces. Virtual screening was performed against successfully docked estimated affinities less than 500 nm filtered. These filtered protein-molecule complexes exported Excel sheets, which then compared any overlapping inhibitors. Four common/overlapping potential identified. Their pose views generated, binding interactions analyzed. compounds their absorption, distribution, metabolism, excretion toxicity (ADME-Tox) properties.
 RESULTS: m240690bcc215667167368734, rxn109fEMOL37110279EMOL314046334 LIND027BT1904LN00213276AK0086 showed good conventional ATP pockets ERK5.
 CONCLUSION: may be proposed 5. Further in silico analysis vitro testing proteins are required confirm inhibitory potential.