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Literature DB >> 20227037

The raf inhibitor paradox: unexpected consequences of targeted drugs.

Abstract

Three papers in Cell and Nature now report that dimeric RAF is a plastic enzyme: blocking one ATP-binding site paradoxically stimulates the kinase activity of the other protomer. This occurs only in "primed" cells bearing activated RAS and WT RAF, explaining the selective efficacy of RAF inhibitors for RAF mutant cells. Copyright 2010 Elsevier Inc. All rights reserved.

Entities: Chemical Gene

Year: 2010 PMID： 20227037 DOI： 10.1016/j.ccr.2010.02.029

Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743

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Cited

16 in total

1. Single substitution within the RKTR motif impairs kinase activity but promotes dimerization of RAF kinase.

Authors: Angela Baljuls; Regina Mahr; Inge Schwarzenau; Thomas Müller; Lisa Polzien; Mirko Hekman; Ulf R Rapp
Journal: J Biol Chem Date: 2011-03-18 Impact factor: 5.157

2. Design and Synthesis of Type-IV Inhibitors of BRAF Kinase That Block Dimerization and Overcome Paradoxical MEK/ERK Activation.

Authors: Chad M Beneker; Magdalini Rovoli; George Kontopidis; Michael Röring; Simeon Galda; Sandra Braun; Tilman Brummer; Campbell McInnes
Journal: J Med Chem Date: 2019-04-12 Impact factor: 7.446

3. Combined MEK and PI3K inhibition in a mouse model of pancreatic cancer.

Authors: Brinda Alagesan; Gianmarco Contino; Alex R Guimaraes; Ryan B Corcoran; Vikram Deshpande; Gregory R Wojtkiewicz; Aram F Hezel; Kwok-Kin Wong; Massimo Loda; Ralph Weissleder; Cyril H Benes; Jeffrey Engelman; Nabeel Bardeesy
Journal: Clin Cancer Res Date: 2014-10-27 Impact factor: 12.531

4. The role of polo-like kinase 3 in the response of BRAF-mutant cells to targeted anticancer therapies.

Authors: Mahamat Babagana; Julia V Kichina; Hannah Slabodkin; Sydney Johnson; Alexei Maslov; Lorin Brown; Kristopher Attwood; Mikhail A Nikiforov; Eugene S Kandel
Journal: Mol Carcinog Date: 2019-09-30 Impact factor: 4.784

5. Distinct requirement for an intact dimer interface in wild-type, V600E and kinase-dead B-Raf signalling.

Authors: Michael Röring; Ricarda Herr; Gina J Fiala; Katharina Heilmann; Sandra Braun; Anja E Eisenhardt; Sebastian Halbach; David Capper; Andreas von Deimling; Wolfgang W Schamel; Darren N Saunders; Tilman Brummer
Journal: EMBO J Date: 2012-04-17 Impact factor: 11.598

The raf inhibitor paradox: unexpected consequences of targeted drugs.

1. Single substitution within the RKTR motif impairs kinase activity but promotes dimerization of RAF kinase.

2. Design and Synthesis of Type-IV Inhibitors of BRAF Kinase That Block Dimerization and Overcome Paradoxical MEK/ERK Activation.

3. Combined MEK and PI3K inhibition in a mouse model of pancreatic cancer.

4. The role of polo-like kinase 3 in the response of BRAF-mutant cells to targeted anticancer therapies.

5. Distinct requirement for an intact dimer interface in wild-type, V600E and kinase-dead B-Raf signalling.

6. Therapeutic strategies for targeting ras proteins.

Review 7. Sorafenib: complexities of Raf-dependent and Raf-independent signaling are now unveiled.

Review 8. Stamping out RAF and MEK1/2 to inhibit the ERK1/2 pathway: an emerging threat to anticancer therapy.

9. Invasive three-dimensional organotypic neoplasia from multiple normal human epithelia.

10. Effect of isouronium/guanidinium substitution on the efficacy of a series of novel anti-cancer agents.