AI Article Synopsis
- Aberrant ERK signaling often causes cancer, and current drugs targeting this pathway face challenges due to drug resistance.
- DEL-22379 is a promising compound that prevents ERK dimerization, remaining effective despite resistance.
- A study was conducted on 47 analogues of DEL-22379 to evaluate their effectiveness against tumor cells, assess their safety, and understand how specific structural features contribute to their ability to inhibit ERK signaling.
Article Abstract
Aberrant activation of ERK signaling pathway usually leads to oncogenesis, and small molecular agents targeting this pathway are impeded by the emergence of drug resistance due to reactivation of ERK signaling. Compound DEL-22379 has been reported to inhibit ERK dimerization which was unaffected by drug-resistant mechanism reactivating the ERK signaling. Here, we discussed a structure-activity relationship study of DEL-22379. Forty-seven analogues were designed and synthesized. Each synthesized compound was biologically evaluated for their inhibitory rates on several tumor cell lines and compounds with high inhibitory rates were further evaluated for IC values. The structure-activity relationship of idolin-2-one scaffold and the impact of Z/E configuration on potency were discussed. Potential safety of two synthesized analogues was investigated and in silico docking study of five compounds was performed to understand the structural basis of ERK dimerization inhibition.
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| http://dx.doi.org/10.1007/s11030-020-10088-0 | DOI Listing |
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