Targeting transcription is no longer a quixotic quest

Mapp, Anna K.; Pricer, Rachel; Sturlis, Steven

doi:10.1038/nchembio.1962

Cited by 21 publications

(27 citation statements)

References 25 publications

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“…selectivity for the target over a non-selective response. PPIs are often dynamic and transient in nature with partner proteins exhibiting weak affinity for each other[1, 115]. The challenge of developing potent selective binders is particularly difficult for strategies that seek to mimic surface residues.…”

Section: Discussionmentioning

confidence: 99%

Systematic Targeting of Protein–Protein Interactions

Modell

Blosser

Arora

2016

Trends in Pharmacological Sciences

156

143

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Over the past decade, protein-protein interactions have gone from being neglected as “undruggable” to being considered attractive targets for the development of therapeutics. Recent advances in computational analysis, fragment-based screening and molecular design have revealed promising strategies to address the basic molecular recognition challenge: how to target large protein surfaces with specificity. Several systematic and complementary workflows have been developed to yield successful inhibitors of protein-protein interactions. Herein we review the major contemporary approaches utilized for the discovery of inhibitors and focus on a structure-based workflow, from the selection of a biological target through design.

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Section: Discussionmentioning

confidence: 99%

Systematic Targeting of Protein–Protein Interactions

Modell

Blosser

Arora

2016

Trends in Pharmacological Sciences

156

143

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“…This discovery provides a possibility for developing targeted therapy of ESCC, even though targeting a transcription factor is a technical challenge. However, recent technical advances have improved the druggability of transcription factors …”

Section: The Lineage‐survival Mechanism As a Targetmentioning

confidence: 99%

“…However, recent technical advances have improved the druggability of transcription factors. 52 As a transcription factor, SOX2 has a DNAbinding transcription domain and functional domains that interact with other cofactors. Eightytwo SOX2-associated nuclear proteins have been identified in two human ESCC cell lines (KYSE70 and TT) using tandem affinity purification followed by liquid chromatography-tandem mass spectrometry.…”

Section: Escc Genomics: An Updatementioning

confidence: 99%

Personalized and targeted therapy of esophageal squamous cell carcinoma: an update

Liu

Xiong

Beasley

et al. 2016

Annals of the New York Academy of Sciences

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Esophageal squamous cell carcinoma (ESCC) is a deadly disease that requires extensive research. In this review, we update recent progress in the research area of targeted therapy for ESCC. Sox2 and its associated proteins (e.g., ΔNp63α), which regulate lineage survival of ESCC cells, are proposed as therapeutic targets. It is believed that targeting the lineage-survival mechanism may be more effective than targeting other mechanisms. With the advent of a new era of personalized targeted therapy, there is a need to move from the tumor-centric model into an organismic model.

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“…Anna Mapp (University of Michigan, Ann Arbor) spoke about strategies for targeting transient protein–protein interactions (PPIs). Taking transcriptional activator–coactivator interactions as a system, Anna reported a strategy in which particular conformations of transcriptional coactivators are engaged thereby modulating the assembly of active transactivator–coactivator complexes . The next speaker was Wesley Robertson from Alanna Schepartz's lab (Yale University).…”

Section: Innovation In Approaches To Drug Discoverymentioning

confidence: 99%