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CC-90009, a novel cereblon E3 ligase modulator, targets acute myeloid leukemia blasts and leukemia stem cells.
Surka C, Jin L, Mbong N, Lu CC, Jang IS, Rychak E, Mendy D, Clayton T, Tindall E, Hsu C, Fontanillo C, Tran E, Contreras A, Ng SWK, Matyskiela M, Wang K, Chamberlain P, Cathers B, Carmichael J, Hansen J, Wang JCY, Minden MD, Fan J, Pierce DW, Pourdehnad M, Rolfe M, Lopez-Girona A, Dick JE, Lu G. Surka C, et al. Among authors: lopez girona a. Blood. 2021 Feb 4;137(5):661-677. doi: 10.1182/blood.2020008676. Blood. 2021. PMID: 33197925 Free PMC article.
CC-122, a pleiotropic pathway modifier, mimics an interferon response and has antitumor activity in DLBCL.
Hagner PR, Man HW, Fontanillo C, Wang M, Couto S, Breider M, Bjorklund C, Havens CG, Lu G, Rychak E, Raymon H, Narla RK, Barnes L, Khambatta G, Chiu H, Kosek J, Kang J, Amantangelo MD, Waldman M, Lopez-Girona A, Cai T, Pourdehnad M, Trotter M, Daniel TO, Schafer PH, Klippel A, Thakurta A, Chopra R, Gandhi AK. Hagner PR, et al. Among authors: lopez girona a. Blood. 2015 Aug 6;126(6):779-89. doi: 10.1182/blood-2015-02-628669. Epub 2015 May 22. Blood. 2015. PMID: 26002965 Free PMC article. Clinical Trial.
CC-90009: A Cereblon E3 Ligase Modulating Drug That Promotes Selective Degradation of GSPT1 for the Treatment of Acute Myeloid Leukemia.
Hansen JD, Correa M, Alexander M, Nagy M, Huang D, Sapienza J, Lu G, LeBrun LA, Cathers BE, Zhang W, Tang Y, Ammirante M, Narla RK, Piccotti JR, Pourdehnad M, Lopez-Girona A. Hansen JD, et al. Among authors: lopez girona a. J Med Chem. 2021 Feb 25;64(4):1835-1843. doi: 10.1021/acs.jmedchem.0c01489. Epub 2021 Feb 16. J Med Chem. 2021. PMID: 33591756
A novel cereblon modulator recruits GSPT1 to the CRL4(CRBN) ubiquitin ligase.
Matyskiela ME, Lu G, Ito T, Pagarigan B, Lu CC, Miller K, Fang W, Wang NY, Nguyen D, Houston J, Carmel G, Tran T, Riley M, Nosaka L, Lander GC, Gaidarova S, Xu S, Ruchelman AL, Handa H, Carmichael J, Daniel TO, Cathers BE, Lopez-Girona A, Chamberlain PP. Matyskiela ME, et al. Among authors: lopez girona a. Nature. 2016 Jul 14;535(7611):252-7. doi: 10.1038/nature18611. Epub 2016 Jun 22. Nature. 2016. PMID: 27338790
Discovery of CRBN E3 Ligase Modulator CC-92480 for the Treatment of Relapsed and Refractory Multiple Myeloma.
Hansen JD, Correa M, Nagy MA, Alexander M, Plantevin V, Grant V, Whitefield B, Huang D, Kercher T, Harris R, Narla RK, Leisten J, Tang Y, Moghaddam M, Ebinger K, Piccotti J, Havens CG, Cathers B, Carmichael J, Daniel T, Vessey R, Hamann LG, Leftheris K, Mendy D, Baculi F, LeBrun LA, Khambatta G, Lopez-Girona A. Hansen JD, et al. Among authors: lopez girona a. J Med Chem. 2020 Jul 9;63(13):6648-6676. doi: 10.1021/acs.jmedchem.9b01928. Epub 2020 Mar 19. J Med Chem. 2020. PMID: 32130004
Cereblon is a direct protein target for immunomodulatory and antiproliferative activities of lenalidomide and pomalidomide.
Lopez-Girona A, Mendy D, Ito T, Miller K, Gandhi AK, Kang J, Karasawa S, Carmel G, Jackson P, Abbasian M, Mahmoudi A, Cathers B, Rychak E, Gaidarova S, Chen R, Schafer PH, Handa H, Daniel TO, Evans JF, Chopra R. Lopez-Girona A, et al. Leukemia. 2012 Nov;26(11):2326-35. doi: 10.1038/leu.2012.119. Epub 2012 May 3. Leukemia. 2012. PMID: 22552008 Free PMC article.
Structure of the human Cereblon-DDB1-lenalidomide complex reveals basis for responsiveness to thalidomide analogs.
Chamberlain PP, Lopez-Girona A, Miller K, Carmel G, Pagarigan B, Chie-Leon B, Rychak E, Corral LG, Ren YJ, Wang M, Riley M, Delker SL, Ito T, Ando H, Mori T, Hirano Y, Handa H, Hakoshima T, Daniel TO, Cathers BE. Chamberlain PP, et al. Among authors: lopez girona a. Nat Struct Mol Biol. 2014 Sep;21(9):803-9. doi: 10.1038/nsmb.2874. Epub 2014 Aug 10. Nat Struct Mol Biol. 2014. PMID: 25108355
Pomalidomide in combination with dexamethasone results in synergistic anti-tumour responses in pre-clinical models of lenalidomide-resistant multiple myeloma.
Rychak E, Mendy D, Shi T, Ning Y, Leisten J, Lu L, Miller K, Narla RK, Orlowski RZ, Raymon HK, Bjorklund CC, Thakurta A, Gandhi AK, Cathers BE, Chopra R, Daniel TO, Lopez-Girona A. Rychak E, et al. Among authors: lopez girona a. Br J Haematol. 2016 Mar;172(6):889-901. doi: 10.1111/bjh.13905. Epub 2016 Feb 23. Br J Haematol. 2016. PMID: 26914976 Free article.
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