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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. 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.
Recently, it was demonstrated that binding of these drugs to CRBN promotes the ubiquitination and subsequent degradation of 2 common substrates, transcription factors Aiolos and Ikaros. Here we report that CC-122, a new chemical entity termed pleiotropic path …
Recently, it was demonstrated that binding of these drugs to CRBN promotes the ubiquitination and subsequent degradation of 2 common …
A Novel Drug, CC-122, Inhibits Tumor Growth in Hepatocellular Carcinoma through Downregulation of an Oncogenic TCF-4 Isoform.
Tomimaru Y, Aihara A, Wands JR, Aloman C, Kim M. Tomimaru Y, et al. Transl Oncol. 2019 Oct;12(10):1345-1356. doi: 10.1016/j.tranon.2019.07.002. Epub 2019 Jul 25. Transl Oncol. 2019. PMID: 31352197 Free PMC article.
LEN and CC-122 significantly reduced the expression levels of TCF-4 J and its target genes (SPP1, AXIN2, MMP7, ASPH, CD24, ANXA1, and CAMK2N1); however, CC-122 was more potent. ...These results suggest that CC-122 inhibits HCC tumo …
LEN and CC-122 significantly reduced the expression levels of TCF-4 J and its target genes (SPP1, AXIN2, MMP7, ASPH, CD …
Avadomide plus obinutuzumab in patients with relapsed or refractory B-cell non-Hodgkin lymphoma (CC-122-NHL-001): a multicentre, dose escalation and expansion phase 1 study.
Michot JM, Bouabdallah R, Vitolo U, Doorduijn JK, Salles G, Chiappella A, Zinzani PL, Bijou F, Kersten MJ, Sarmiento R, Mosulen S, Mendez C, Uttamsingh S, Pourdehnad M, Hege K, Chen T, Klein C, Hagner PR, Nikolova Z, Ribrag V. Michot JM, et al. Lancet Haematol. 2020 Sep;7(9):e649-e659. doi: 10.1016/S2352-3026(20)30208-8. Epub 2020 Aug 3. Lancet Haematol. 2020. PMID: 32758434 Clinical Trial.
BACKGROUND: Avadomide (CC-122) is a novel oral cereblon-modulating agent with promising activity in non-Hodgkin lymphoma. ...The median number of previous anticancer regimens was three (IQR 2-4). The maximum tolerated dose and non-tolerated dose were n …
BACKGROUND: Avadomide (CC-122) is a novel oral cereblon-modulating agent with promising activity in non-Hodgkin lymphoma. ...T …
Single-Dose Pharmacokinetics, Safety, and Tolerability of Avadomide (CC-122) in Subjects With Mild, Moderate, or Severe Renal Impairment.
Li Y, MacGorman K, Liu L, Chen J, Hoffmann M, Palmisano M, Zhou S. Li Y, et al. Clin Pharmacol Drug Dev. 2020 Oct;9(7):785-796. doi: 10.1002/cpdd.760. Epub 2019 Dec 31. Clin Pharmacol Drug Dev. 2020. PMID: 31891240
Given that renal clearance is one of the major routes of elimination for CC-122 and its clearance/exposure could be affected by renal impairment, a total of 50 subjects with various degrees of renal function were enrolled in an open-label, single-dose study to evalu …
Given that renal clearance is one of the major routes of elimination for CC-122 and its clearance/exposure could be affected b …
CC-122 immunomodulatory effects in refractory patients with diffuse large B-cell lymphoma.
Cubillos-Zapata C, Cordoba R, Avendaño-Ortiz J, Arribas-Jiménez C, Hernández-Jiménez E, Toledano V, Villaescusa T, Moreno V, López-Collazo E. Cubillos-Zapata C, et al. Oncoimmunology. 2016 Sep 16;5(12):e1231290. doi: 10.1080/2162402X.2016.1231290. eCollection 2016. Oncoimmunology. 2016. PMID: 28255524 Free PMC article.
The chemical structure of CC-122 includes the glutarimide moiety that is known to modulate the immune response. ...Finally, the activation of T cells through co-stimulatory molecule (CD28) was detected as a delayed CC-122 effect. In this context, CC
The chemical structure of CC-122 includes the glutarimide moiety that is known to modulate the immune response. ...Finally, th …
[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.
The primary direct target protein of thalidomide and IMiDs is cereblon (CRBN), a substrate receptor of Cullin-RING ligase 4 (CRL4). CRL4(CRBN) is a unique E3 ubiquitin ligase because its substrate selectivity is altered by ligands such as IMiDs. ...Because the activity of …
The primary direct target protein of thalidomide and IMiDs is cereblon (CRBN), a substrate receptor of Cullin-RING ligase 4 (CRL4). C …
Lenalidomide induces ubiquitination and degradation of CK1α in del(5q) MDS.
Krönke J, Fink EC, Hollenbach PW, MacBeth KJ, Hurst SN, Udeshi ND, Chamberlain PP, Mani DR, Man HW, Gandhi AK, Svinkina T, Schneider RK, McConkey M, Järås M, Griffiths E, Wetzler M, Bullinger L, Cathers BE, Carr SA, Chopra R, Ebert BL. Krönke J, et al. Nature. 2015 Jul 9;523(7559):183-188. doi: 10.1038/nature14610. Epub 2015 Jul 1. Nature. 2015. PMID: 26131937 Free PMC article.
We found that mouse cells are resistant to lenalidomide but that changing a single amino acid in mouse Crbn to the corresponding human residue enables lenalidomide-dependent degradation of CK1alpha. We further demonstrate that minor side chain modifications in thalidomide …
We found that mouse cells are resistant to lenalidomide but that changing a single amino acid in mouse Crbn to the corresponding huma …
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
IMiDs New and Old.
Yamshon S, Ruan J. Yamshon S, et al. Curr Hematol Malig Rep. 2019 Oct;14(5):414-425. doi: 10.1007/s11899-019-00536-6. Curr Hematol Malig Rep. 2019. PMID: 31302872 Review.
RECENT FINDINGS: Improved upon the prototype thalidomide, the second-generation compound lenalidomide has enhanced immunological and anti-cancer properties with fewer side effects, while next-generation small molecule cereblon/E3 ubiquitin ligase modulator CC-122 is …
RECENT FINDINGS: Improved upon the prototype thalidomide, the second-generation compound lenalidomide has enhanced immunological and anti-ca …
Exposure-response analysis to assess the concentration-QTc relationship of CC-122.
Li Y, Carayannopoulos LN, Thomas M, Palmisano M, Zhou S. Li Y, et al. Clin Pharmacol. 2016 Sep 9;8:117-25. doi: 10.2147/CPAA.S111867. eCollection 2016. Clin Pharmacol. 2016. PMID: 27672344 Free PMC article.
CC-122 hydrochloride is a novel pleiotropic pathway modifier compound that binds cereblon, a substrate receptor of the Cullin 4 RING E3 ubiquitin ligase complex. ...To assess the potential concentration-QTc relationship in humans and to ascertain or exclude a
CC-122 hydrochloride is a novel pleiotropic pathway modifier compound that binds cereblon, a substrate receptor of the Cullin
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