Literature DB >> 26438514

The novel mechanism of lenalidomide activity.

Emma C Fink1, Benjamin L Ebert1.   

Abstract

Lenalidomide acts by a novel drug mechanism-modulation of the substrate specificity of the CRL4(CRBN) E3 ubiquitin ligase. In multiple myeloma, lenalidomide induces the ubiquitination of IKZF1 and IKZF3 by CRL4(CRBN). Subsequent proteasomal degradation of these transcription factors kills multiple myeloma cells. In del(5q) myelodysplastic syndrome, lenalidomide induces the degradation of CK1α, which preferentially affects del(5q) cells because they express this gene at haploinsufficient levels. In the future, modulation of ubiquitin ligase function may enable us to target previously "undruggable" proteins.
© 2015 by The American Society of Hematology.

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Year:  2015        PMID： 26438514      PMCID： PMC4653765          DOI： 10.1182/blood-2015-07-567958

Source DB:  PubMed          Journal:  Blood        ISSN： 0006-4971            Impact factor:   22.113


  35 in total

1.  Lenalidomide in the myelodysplastic syndrome with chromosome 5q deletion.

Authors:  Alan List; Gordon Dewald; John Bennett; Aristotle Giagounidis; Azra Raza; Eric Feldman; Bayard Powell; Peter Greenberg; Deborah Thomas; Richard Stone; Craig Reeder; Kenton Wride; John Patin; Michele Schmidt; Jerome Zeldis; Robert Knight
Journal:  N Engl J Med       Date:  2006-10-05       Impact factor: 91.245

2.  Clinical efficacy of lenalidomide in patients with relapsed or refractory chronic lymphocytic leukemia: results of a phase II study.

Authors:  Asher Chanan-Khan; Kena C Miller; Laurie Musial; David Lawrence; Swaminathan Padmanabhan; Kenichi Takeshita; Carl W Porter; David W Goodrich; Zale P Bernstein; Paul Wallace; David Spaner; Alice Mohr; Catriona Byrne; Francisco Hernandez-Ilizaliturri; Cynthia Chrystal; Petr Starostik; Myron S Czuczman
Journal:  J Clin Oncol       Date:  2006-11-06       Impact factor: 44.544

3.  IRF4 addiction in multiple myeloma.

Authors:  Arthur L Shaffer; N C Tolga Emre; Laurence Lamy; Vu N Ngo; George Wright; Wenming Xiao; John Powell; Sandeep Dave; Xin Yu; Hong Zhao; Yuxin Zeng; Bangzheng Chen; Joshua Epstein; Louis M Staudt
Journal:  Nature       Date:  2008-06-22       Impact factor: 49.962

4.  Lenalidomide plus dexamethasone for relapsed multiple myeloma in North America.

Authors:  Donna M Weber; Christine Chen; Ruben Niesvizky; Michael Wang; Andrew Belch; Edward A Stadtmauer; David Siegel; Ivan Borrello; S Vincent Rajkumar; Asher Alban Chanan-Khan; Sagar Lonial; Zhinuan Yu; John Patin; Marta Olesnyckyj; Jerome B Zeldis; Robert D Knight
Journal:  N Engl J Med       Date:  2007-11-22       Impact factor: 91.245

5.  Lenalidomide induces complete and partial remissions in patients with relapsed and refractory chronic lymphocytic leukemia.

Authors:  Alessandra Ferrajoli; Bang-Ning Lee; Ellen J Schlette; Susan M O'Brien; Hui Gao; Sijin Wen; William G Wierda; Zeev Estrov; Stefan Faderl; Evan N Cohen; Changping Li; James M Reuben; Michael J Keating
Journal:  Blood       Date:  2008-03-11       Impact factor: 22.113

6.  Identification of miR-145 and miR-146a as mediators of the 5q- syndrome phenotype.

Authors:  Daniel T Starczynowski; Florian Kuchenbauer; Bob Argiropoulos; Sandy Sung; Ryan Morin; Andrew Muranyi; Martin Hirst; Donna Hogge; Marco Marra; Richard A Wells; Rena Buckstein; Wan Lam; R Keith Humphries; Aly Karsan
Journal:  Nat Med       Date:  2009-11-08       Impact factor: 53.440

7.  Lenalidomide oral monotherapy produces a high response rate in patients with relapsed or refractory mantle cell lymphoma.

Authors:  Thomas M Habermann; Izidore S Lossos; Glen Justice; Julie M Vose; Peter H Wiernik; Kyle McBride; Kenton Wride; Annette Ervin-Haynes; Kenichi Takeshita; Dennis Pietronigro; Jerome B Zeldis; Joseph M Tuscano
Journal:  Br J Haematol       Date:  2009-02-24       Impact factor: 6.998

8.  Thalidomide costimulates primary human T lymphocytes, preferentially inducing proliferation, cytokine production, and cytotoxic responses in the CD8+ subset.

Authors:  P A Haslett; L G Corral; M Albert; G Kaplan
Journal:  J Exp Med       Date:  1998-06-01       Impact factor: 14.307

9.  Thalidomide selectively inhibits tumor necrosis factor alpha production by stimulated human monocytes.

Authors:  E P Sampaio; E N Sarno; R Galilly; Z A Cohn; G Kaplan
Journal:  J Exp Med       Date:  1991-03-01       Impact factor: 14.307

10.  Identification of RPS14 as a 5q- syndrome gene by RNA interference screen.

Authors:  Benjamin L Ebert; Jennifer Pretz; Jocelyn Bosco; Cindy Y Chang; Pablo Tamayo; Naomi Galili; Azra Raza; David E Root; Eyal Attar; Steven R Ellis; Todd R Golub
Journal:  Nature       Date:  2008-01-17       Impact factor: 49.962
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  40 in total

Review 1.  Applications of chemogenomic library screening in drug discovery.

Authors:  Lyn H Jones; Mark E Bunnage
Journal:  Nat Rev Drug Discov       Date:  2017-01-20       Impact factor: 84.694

Review 2.  Breaking the Fourth Wall: Modulating Quaternary Associations for Protein Regulation and Drug Discovery.

Authors:  Marcus J C Long; Dziyana Hnedzko; Bo Kyoung Kim; Yimon Aye
Journal:  Chembiochem       Date:  2019-04-01       Impact factor: 3.164

3.  Using pharmacy management systems for research: survival outcomes for lenalidomide in multiple myeloma in the clinical setting.

Authors:  Megan M Sharkey; Daniel McKavanagh; Euan Walpole; Peter Mollee; Samantha A Hollingworth
Journal:  Int J Clin Pharm       Date:  2017-06-01

Review 4.  Cancer therapies based on targeted protein degradation - lessons learned with lenalidomide.

Authors:  Max Jan; Adam S Sperling; Benjamin L Ebert
Journal:  Nat Rev Clin Oncol       Date:  2021-03-02       Impact factor: 66.675

5.  Molecularly targeted therapies for relapsed and refractory peripheral T-cell lymphomas.

Authors:  Zachary D Epstein-Peterson; Steven M Horwitz
Journal:  Semin Hematol       Date:  2021-03-03       Impact factor: 3.851

6.  Reversible ON- and OFF-switch chimeric antigen receptors controlled by lenalidomide.

Authors:  Max Jan; Irene Scarfò; Rebecca C Larson; Amanda Walker; Andrea Schmidts; Andrew A Guirguis; Jessica A Gasser; Mikołaj Słabicki; Amanda A Bouffard; Ana P Castano; Michael C Kann; Maria L Cabral; Alexander Tepper; Daniel E Grinshpun; Adam S Sperling; Taeyoon Kyung; Quinlan L Sievers; Michael E Birnbaum; Marcela V Maus; Benjamin L Ebert
Journal:  Sci Transl Med       Date:  2021-01-06       Impact factor: 17.956

7.  Prognostic and predictive performance of R-ISS with SKY92 in older patients with multiple myeloma: the HOVON-87/NMSG-18 trial.

Authors:  Rowan Kuiper; Sonja Zweegman; Mark van Duin; Martin H van Vliet; Erik H van Beers; Belinda Dumee; Michael Vermeulen; Jasper Koenders; Bronno van der Holt; Heleen Visser-Wisselaar; Markus Hansson; Annette W G van der Velden; H Berna Beverloo; Marian Stevens-Kroef; Mark-David Levin; Annemiek Broijl; Anders Waage; Pieter Sonneveld
Journal:  Blood Adv       Date:  2020-12-22

Review 8.  The functional mechanisms of mutations in myelodysplastic syndrome.

Authors:  Yasunobu Nagata; Jaroslaw P Maciejewski
Journal:  Leukemia       Date:  2019-10-31       Impact factor: 11.528

9.  Defining the human C2H2 zinc finger degrome targeted by thalidomide analogs through CRBN.

Authors:  Quinlan L Sievers; Georg Petzold; Richard D Bunker; Aline Renneville; Mikołaj Słabicki; Brian J Liddicoat; Wassim Abdulrahman; Tarjei Mikkelsen; Benjamin L Ebert; Nicolas H Thomä
Journal:  Science       Date:  2018-11-02       Impact factor: 47.728

Review 10.  Germline IKZF1 mutations and their impact on immunity: IKAROS-associated diseases and pathophysiology.

Authors:  Hye Sun Kuehn; Cristiane J Nunes-Santos; Sergio D Rosenzweig
Journal:  Expert Rev Clin Immunol       Date:  2021-03-19       Impact factor: 4.473
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