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A Cereblon Modulator (CC-220) with Improved Degradation of Ikaros and Aiolos.
Matyskiela ME, Zhang W, Man HW, Muller G, Khambatta G, Baculi F, Hickman M, LeBrun L, Pagarigan B, Carmel G, Lu CC, Lu G, Riley M, Satoh Y, Schafer P, Daniel TO, Carmichael J, Cathers BE, Chamberlain PP. Matyskiela ME, et al. J Med Chem. 2018 Jan 25;61(2):535-542. doi: 10.1021/acs.jmedchem.6b01921. Epub 2017 Apr 20. J Med Chem. 2018. PMID: 28425720
The drugs lenalidomide and pomalidomide bind to the protein cereblon, directing the CRL4-CRBN E3 ligase toward the transcription factors Ikaros and Aiolos to cause their ubiquitination and degradation. Here we describe CC-220 (compound 6), a cereblon modulator in cl …
The drugs lenalidomide and pomalidomide bind to the protein cereblon, directing the CRL4-CRBN E3 ligase toward the transcription factors Ika …
Iberdomide (CC-220) is a potent cereblon E3 ligase modulator with antitumor and immunostimulatory activities in lenalidomide- and pomalidomide-resistant multiple myeloma cells with dysregulated CRBN.
Bjorklund CC, Kang J, Amatangelo M, Polonskaia A, Katz M, Chiu H, Couto S, Wang M, Ren Y, Ortiz M, Towfic F, Flynt JE, Pierceall W, Thakurta A. Bjorklund CC, et al. Leukemia. 2020 Apr;34(4):1197-1201. doi: 10.1038/s41375-019-0620-8. Epub 2019 Nov 12. Leukemia. 2020. PMID: 31719682 Free PMC article. No abstract available.
[Cereblon as a primary target of IMiDs].
Ito T, Handa H. Ito T, et al. Rinsho Ketsueki. 2019;60(9):1013-1019. doi: 10.11406/rinketsu.60.1013. Rinsho Ketsueki. 2019. PMID: 31597822 Review. Japanese.
Because the activity of new CRBN-binding compounds is not limited to immunomodulation, the designation of "cereblon modulators" has been proposed for these small CRBN-binding compounds. Currently, researchers are investigating CC-122 (avadomide) and CC-220 ( …
Because the activity of new CRBN-binding compounds is not limited to immunomodulation, the designation of "cereblon modulators" has been pro …
Novel immunomodulatory drugs and neo-substrates.
Gao S, Wang S, Song Y. Gao S, et al. Biomark Res. 2020 Jan 9;8:2. doi: 10.1186/s40364-020-0182-y. eCollection 2020. Biomark Res. 2020. PMID: 31938543 Free PMC article. Review.
Recently, novel thalidomide analogs have been designed for better clinical efficacy, including CC-122, CC-220 and CC-885. Moreover, a number of neo-substrates of IMiDs have been discovered. ...
Recently, novel thalidomide analogs have been designed for better clinical efficacy, including CC-122, CC-220 and CC
Treatment of Lymphoid and Myeloid Malignancies by Immunomodulatory Drugs.
Fuchs O. Fuchs O. Cardiovasc Hematol Disord Drug Targets. 2019;19(1):51-78. doi: 10.2174/1871529X18666180522073855. Cardiovasc Hematol Disord Drug Targets. 2019. PMID: 29788898 Review.
Thalidomide and its derivatives (lenalidomide, pomalidomide, avadomide, iberdomide hydrochoride, CC-885 and CC-90009) form the family of immunomodulatory drugs (IMiDs). ...
Thalidomide and its derivatives (lenalidomide, pomalidomide, avadomide, iberdomide hydrochoride, CC-885 and CC-90009) f …
Identification of lenalidomide resistance pathways in myeloma and targeted resensitization using cereblon replacement, inhibition of STAT3 or targeting of IRF4.
Zhu YX, Shi CX, Bruins LA, Wang X, Riggs DL, Porter B, Ahmann JM, de Campos CB, Braggio E, Bergsagel PL, Stewart AK. Zhu YX, et al. Blood Cancer J. 2019 Feb 11;9(2):19. doi: 10.1038/s41408-019-0173-0. Blood Cancer J. 2019. PMID: 30741931 Free PMC article.
Four HMCLs were demonstrated to be resistant to all IMiDs including lenalidomide, pomalidomide, and CC-220, but not to Bortezomib. In three HMLCs (MM.1.SLenRes, KMS11LenRes and OPM2LenRes), CRBN abnormalities were found, including chromosomal deletion, point mutatio …
Four HMCLs were demonstrated to be resistant to all IMiDs including lenalidomide, pomalidomide, and CC-220, but not to Bortezo …
Cereblon modulator iberdomide induces degradation of the transcription factors Ikaros and Aiolos: immunomodulation in healthy volunteers and relevance to systemic lupus erythematosus.
Schafer PH, Ye Y, Wu L, Kosek J, Ringheim G, Yang Z, Liu L, Thomas M, Palmisano M, Chopra R. Schafer PH, et al. Ann Rheum Dis. 2018 Oct;77(10):1516-1523. doi: 10.1136/annrheumdis-2017-212916. Epub 2018 Jun 26. Ann Rheum Dis. 2018. PMID: 29945920 Free PMC article. Clinical Trial.
OBJECTIVES: IKZF1 and IKZF3 (encoding transcription factors Ikaros and Aiolos) are susceptibility loci for systemic lupus erythematosus (SLE). The pharmacology of iberdomide (CC-220), a cereblon (CRBN) modulator targeting Ikaros and Aiolos, was studied in SLE …
OBJECTIVES: IKZF1 and IKZF3 (encoding transcription factors Ikaros and Aiolos) are susceptibility loci for systemic lupus erythematosus (SLE …
New drugs in early development for treating multiple myeloma: all that glitters is not gold.
Bertamini L, Bonello F, Boccadoro M, Bringhen S. Bertamini L, et al. Expert Opin Investig Drugs. 2020 Sep;29(9):989-1004. doi: 10.1080/13543784.2020.1772753. Epub 2020 Sep 30. Expert Opin Investig Drugs. 2020. PMID: 32434394 Review.
The paper culminates with our perspective on therapeutic approaches on the horizon for this disease. EXPERT OPINION: IMD iberdomide and the export protein inhibitor selinexor demonstrated efficacy in heavily pretreated patients who had no other therapeutic options. ...
The paper culminates with our perspective on therapeutic approaches on the horizon for this disease. EXPERT OPINION: IMD iberdomide a …
Aiolos Overexpression in Systemic Lupus Erythematosus B Cell Subtypes and BAFF-Induced Memory B Cell Differentiation Are Reduced by CC-220 Modulation of Cereblon Activity.
Nakayama Y, Kosek J, Capone L, Hur EM, Schafer PH, Ringheim GE. Nakayama Y, et al. J Immunol. 2017 Oct 1;199(7):2388-2407. doi: 10.4049/jimmunol.1601725. Epub 2017 Aug 28. J Immunol. 2017. PMID: 28848067 Free PMC article.
B cell differentiation transcription factors in memory, DN, and naive B cells in SLE show elevated levels of Aiolos, whereas Ikaros levels are unchanged. Treatment with CC-220, a modulator of the cullin ring ligase 4-cereblon E3 ubiquitin ligase complex, reduces Aio …
B cell differentiation transcription factors in memory, DN, and naive B cells in SLE show elevated levels of Aiolos, whereas Ikaros levels a …
[Recent topics in IMiDs and cereblon].
Ito T, Handa H. Ito T, et al. Rinsho Ketsueki. 2017;58(10):2067-2073. doi: 10.11406/rinketsu.58.2067. Rinsho Ketsueki. 2017. PMID: 28978850 Japanese.
Recently, novel CRBN-binding compounds have been developed and are called "cereblon modulators". Among these, CC-122 and CC-220 are currently under clinical development for the treatment of diffuse large B-cell lymphoma and systemic lupus erythematosus, respe …
Recently, novel CRBN-binding compounds have been developed and are called "cereblon modulators". Among these, CC-122 and CC- …
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