ArticleACS chemical biology2012
Targeting diverse signaling interaction sites allows the rapid generation of bivalent kinase inhibitors.
Article in ACS chemical biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 28 citations in OpenAlex.
- Linking ATP and allosteric sites to achieve superadditive binding with bivalent EGFR kinase inhibitors.Communications chemistry · 2024Article
- Linking ATP and allosteric sites to achieve superadditive binding with bivalent EGFR kinase inhibitors.Research square · 2023Article
- Chemical Modification of Phage-Displayed Helix-Loop-Helix Peptides to Construct Kinase-Focused Libraries.Chembiochem : a European journal of chemical biology · 2021Article
- Article
- Conformationally constrained peptides target the allosteric kinase dimer interface and inhibit EGFR activation.Bioorganic & medicinal chemistry · 2018Article
- Conversion of a Single Polypharmacological Agent into Selective Bivalent Inhibitors of Intracellular Kinase Activity.ACS chemical biology · 2016Article
- Examining the influence of specificity ligands and ATP-competitive ligands on the overall effectiveness of bivalent kinase inhibitors.Proteome science · 2016Article
- The ins and outs of selective kinase inhibitor development.Nature chemical biology · 2015Article
- Ten things you should know about protein kinases: IUPHAR Review 14.British journal of pharmacology · 2015Review
- Divergent modulation of Src-family kinase regulatory interactions with ATP-competitive inhibitors.ACS chemical biology · 2014Article
- Label transfer reagents to probe p38 MAPK binding partners.Chembiochem : a European journal of chemical biology · 2013Article
- A peptide photoaffinity probe specific for the active conformation of the Abl tyrosine kinase.Chembiochem : a European journal of chemical biology · 2012Article
- Bivalent inhibitors of protein kinases.Critical reviews in biochemistry and molecular biologyReview
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The identification of potent and selective modulators of protein kinase function remains a challenge, and new strategies are needed for generating these useful ligands. Here, we describe the generation of bivalent inhibitors of three unrelated protein kinases: the CAMK family kinase Pim1, the mitogen-activated protein kinase (MAPK) p38α, and the receptor tyrosine kinase (RTK) epidermal growth factor receptor (EGFR). These bivalent inhibitors consist of an ATP-competitive inhibitor that is covalently tethered to an engineered form of the self-labeling protein O(6)-alkylguanine-DNA alkyltransferase (SNAP-tag). In each example, SNAP-tag is fused to a peptide ligand that binds to a signaling interaction site of the kinase being targeted. These interactions increase the overall selectivity and potency of the bivalent inhibitors that were generated. The ability to exploit disparate binding sites in diverse kinases points to the generality of the method described. Finally, we demonstrate that ATP-competitive inhibitors that are conjugated to the bio-orthogonal tag O(4)-benzyl-2-chloro-6-aminopyrimidine (CLP) are cell-permeable. The selective labeling of SNAP-tag with CLP conjugates allows the rapid assembly of bivalent inhibitors in living cells.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.