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Front Cover: Combined Scaffold Evaluation and Systems‐Level Transcriptome‐Based Analysis for Accelerated Lead Optimization Reveals Ribosomal Targeting Spirooxindole Cyclopropanes (ChemMedChem 18/2019)
Author(s) -
Rodriguez Kevin X.,
Howe Erin N.,
Bacher Emily P.,
Burnette Miranda,
Meloche Jennifer L.,
Meisel Jayda,
Schnepp Patricia,
Tan Xuejuan,
Chang Mayland,
Zartman Jeremiah,
Zhang Siyuan,
Ashfeld Brandon L.
Publication year - 2019
Publication title -
chemmedchem
Language(s) - English
Resource type - Reports
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201900502
Subject(s) - computational biology , transcriptome , identification (biology) , lead compound , function (biology) , drug discovery , mechanism (biology) , lead (geology) , front cover , ribosomal protein , ribosomal rna , small molecule , biology , chemistry , bioinformatics , cover (algebra) , biochemistry , in vitro , genetics , gene , ribosome , rna , mechanical engineering , paleontology , gene expression , engineering , botany , philosophy , epistemology
The Front Cover highlights the inherent value of an integrated, biologically‐inspired synthesis and assay strategy for the identification of lead drug candidates that relies on the elucidation of a molecular mechanism of action as a potential avenue for the design of new and more effective anticancer chemotherapeutics. A combination of advanced DeMAND transcriptome analysis derived from protein synthesis assays, and the phenotypic output from a rationally designed collection of spirocyclopropyl oxindoles, indicated that the disruption of ribosomal function was the likely mechanism for inhibition of cancer cell proliferation. The parallel assessment of small molecule phenotypic evaluation through a biologically inspired target‐directed synthesis, and global bioinformatics analysis of transcriptome networks represents an alternative strategy for the identification of potent bioactive lead candidates with clear molecular level details of mechanism. More information can be found in the Full Paper by Jeremiah Zartman, Siyuan Zhang, Brandon L. Ashfeld et al. on page 1653 in Issue 18, 2019 (DOI: 10.1002/cmdc.201900266).