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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: havens cg. 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
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: havens cg. 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.
Immunomodulatory agents lenalidomide and pomalidomide co-stimulate T cells by inducing degradation of T cell repressors Ikaros and Aiolos via modulation of the E3 ubiquitin ligase complex CRL4(CRBN.).
Gandhi AK, Kang J, Havens CG, Conklin T, Ning Y, Wu L, Ito T, Ando H, Waldman MF, Thakurta A, Klippel A, Handa H, Daniel TO, Schafer PH, Chopra R. Gandhi AK, et al. Among authors: havens cg. Br J Haematol. 2014 Mar;164(6):811-21. doi: 10.1111/bjh.12708. Epub 2013 Dec 13. Br J Haematol. 2014. PMID: 24328678 Free PMC article.
Rate of CRL4(CRBN) substrate Ikaros and Aiolos degradation underlies differential activity of lenalidomide and pomalidomide in multiple myeloma cells by regulation of c-Myc and IRF4.
Bjorklund CC, Lu L, Kang J, Hagner PR, Havens CG, Amatangelo M, Wang M, Ren Y, Couto S, Breider M, Ning Y, Gandhi AK, Daniel TO, Chopra R, Klippel A, Thakurta AG. Bjorklund CC, et al. Among authors: havens cg. Blood Cancer J. 2015 Oct 2;5(10):e354. doi: 10.1038/bcj.2015.66. Blood Cancer J. 2015. PMID: 26430725 Free PMC article.
Thymine DNA glycosylase is a CRL4Cdt2 substrate.
Slenn TJ, Morris B, Havens CG, Freeman RM Jr, Takahashi TS, Walter JC. Slenn TJ, et al. Among authors: havens cg. J Biol Chem. 2014 Aug 15;289(33):23043-23055. doi: 10.1074/jbc.M114.574194. Epub 2014 Jun 19. J Biol Chem. 2014. PMID: 24947512 Free PMC article.
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