MASPIT: three-hybrid trap for quantitative proteome fingerprinting of small molecule-protein interactions in mammalian cells.
Article Details
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Caligiuri M, Molz L, Liu Q, Kaplan F, Xu JP, Majeti JZ, Ramos-Kelsey R, Murthi K, Lievens S, Tavernier J, Kley N
MASPIT: three-hybrid trap for quantitative proteome fingerprinting of small molecule-protein interactions in mammalian cells.
Chem Biol. 2006 Jul;13(7):711-22.
- PubMed ID
- 16873019 [ View in PubMed]
- Abstract
Organic small molecules generally act by perturbing the function of one or more cellular target proteins, the identification of which is essential to an understanding of the molecular basis of drug action. Here we describe the application of methotrexate-linked small molecule ligands to a mammalian three-hybrid interaction trap for proteome-wide identification of small molecule targets, quantification of the targeting potency of unmodified small molecules for such targets in intact cells, and screening for inhibitors of small molecule-protein interactions. During the course of this study we also identified the pyrido[2,3-d]pyrimidine PD173955, a known SRC kinase inhibitor, as a potent inhibitor of several ephrin receptor tyrosine kinases. This finding could perhaps be exploited in the design of inhibitors for this kinase subfamily, members of which have been implicated in the pathogenesis of various diseases, including cancer.
DrugBank Data that Cites this Article
- Binding Properties
Drug Target Property Measurement pH Temperature (°C) Imatinib Tyrosine-protein kinase ABL1 IC 50 (nM) 372 N/A N/A Details Imatinib Tyrosine-protein kinase ABL1 EC 50 (nM) 7.00E+01 N/A N/A Details