Conformational control inhibition of the BCR-ABL1 tyrosine kinase, including the gatekeeper T315I mutant, by the switch-control inhibitor DCC-2036.

doi:10.1016/j.ccr.2011.03.003

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Article

Conformational control inhibition of the BCR-ABL1 tyrosine kinase, including the gatekeeper T315I mutant, by the switch-control inhibitor DCC-2036.

Cancer cell - 12 Apr 2011

Chan Wayne W, Wise Scott C, Kaufman Michael D, Ahn Yu Mi, Ensinger Carol L, Haack Torsten, Hood Molly M, Jones Jennifer, Lord John W, Lu Wei Ping, Miller David, Patt William C, Smith Bryan D, Petillo Peter A, Rutkoski Thomas J, Telikepalli Hanumaiah, Vogeti Lakshminarayana, Yao Tony, Chun Lawrence, Clark Robin, Evangelista Peter, Gavrilescu L Cristina, Lazarides Katherine, Zaleskas Virginia M, Stewart Lance J, Van Etten Richard A, Flynn Daniel L

Abstract excerpt

Acquired resistance to ABL1 tyrosine kinase inhibitors (TKIs) through ABL1 kinase domain mutations, particularly the gatekeeper mutant T315I, is a significant problem for patients with chronic myeloid leukemia (CML). Using structure-based drug design, we developed compounds that bind to residues (Arg386/Glu282) ABL1 uses to switch between inactive and active conformations. The lead "switch-control" inhibitor,...

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Identifiers

PMID: 21481795
DOI: 10.1016/j.ccr.2011.03.003
PMCID: PMC3077923

Genes

ABL1
DCC
BCR

Variants

Provenance

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Conformational control inhibition of the BCR-ABL1 tyrosine kinase, including the gatekeeper T315I mutant, by the switch-control inhibitor DCC-2036.PMID 21481795Read ↗

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