Biochemical and transcriptional profiling to triage additional activities in a series of IGF-1R/IR inhibitors

Ross‐Macdonald, Petra; Silva, Heshani de; Patel, Vishal; Truong, Amy; He, Aiqing; Neuhaus, Isaac M.; Tilford, Charles; Ji, Rui-Ru; Siemers, Nathan O.; Greer, Ann; Carboni, Joan M.; Gottardis, Marco M.; Menard, Krista; Lee, Frank; Dodier, Marco; Frennesson, David B.; Sampognaro, Anthony J.; Saulnier, Mark G.; Trainor, George L.; Vyas, Dolatrai M.; Zimmermann, Kurt; Wittman, Mark D.

doi:10.1016/j.bmc.2011.10.090

Cited by 2 publications

(2 citation statements)

References 21 publications

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“…Indeed, with the development of novel synthetic methods, a repertoire of fluorinated prolines dramatically increased during the past two decades. It is impossible to consider in this Perspective each individual example in details, but the list of recent bioactive structures with a fragment of fluorinated proline along with a brief description of their application are outlined in Figure . − …”

Section: Application In Medicinal Chemistry and Agrochemistrymentioning

confidence: 99%

Fluorine-Containing Prolines: Synthetic Strategies, Applications, and Opportunities

Mykhailiuk

2022

J. Org. Chem.

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Fluorinated prolines play an important role in peptide studies, protein engineering, medicinal chemistry, drug discovery, and agrochemistry. Since the first synthesis of 4-fluoroprolines by Gottlieb and Witkop in 1965, their popularity started to grow exponentially. For example, during the past two decades, all isomeric trifluoromethyl-substituted prolines have been synthesized. In this Perspective, chemical properties and applications of fluorinated prolines are discussed. Synthetic approaches to all known fluorine-containing prolines are also discussed and analyzed. This analysis unexpectedly revealed an unsolved problem: in strict contrast to fluoro- and trifluoromethyl-substituted prolines, the corresponding analogues with fluoromethyl and difluoromethyl groups are mostly unknown. At the end of the paper, structures of several interesting, yet unknown, fluorinated prolines are discloseda good opportunity for chemists to make them.

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Section: Application In Medicinal Chemistry and Agrochemistrymentioning

confidence: 99%

Fluorine-Containing Prolines: Synthetic Strategies, Applications, and Opportunities

Mykhailiuk

2022

J. Org. Chem.

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“…The use of informatics can then be applied to lead optimization by guiding chemical modifications necessary to achieve the desired effects. 42,43 In the following section, we highlight and critically discuss innovative profiling systems, including those based on chemical-genomics-, transcriptomics-, proteomics-, metabolomics-, cell line panel-, and cell imaging-based profiling.…”

Section: Multidimensional Profiling Approaches For Target Identificationmentioning

confidence: 99%

Target identification of small molecules based on chemical biology approaches

2013

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Recently, a phenotypic approach-screens that assess the effects of compounds on cells, tissues, or whole organisms-has been reconsidered and reintroduced as a complementary strategy of a target-based approach for drug discovery. Although the finding of novel bioactive compounds from large chemical libraries has become routine, the identification of their molecular targets is still a time-consuming and difficult process, making this step rate-limiting in drug development. In the last decade, we and other researchers have amassed a large amount of phenotypic data through progress in omics research and advances in instrumentation. Accordingly, the profiling methodologies using these datasets expertly have emerged to identify and validate specific molecular targets of drug candidates, attaining some progress in current drug discovery (e.g., eribulin). In the case of a compound that shows an unprecedented phenotype likely by inhibiting a first-in-class target, however, such phenotypic profiling is invalid. Under the circumstances, a photo-crosslinking affinity approach should be beneficial. In this review, we describe and summarize recent progress in both affinity-based (direct) and phenotypic profiling (indirect) approaches for chemical biology target identification.

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Biochemical and transcriptional profiling to triage additional activities in a series of IGF-1R/IR inhibitors

Cited by 2 publications

References 21 publications

Fluorine-Containing Prolines: Synthetic Strategies, Applications, and Opportunities

Fluorine-Containing Prolines: Synthetic Strategies, Applications, and Opportunities

Target identification of small molecules based on chemical biology approaches

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