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IAP antagonist GDC-0917 is more potent than Debio1143 in promoting cell death, c-IAP1 degradation and tumor growth inhibition.

作者信息

Alicke Bruno, Varfolomeev Eugene, Lee Shi Hui Kaylee, Frommlet Alexandra, Ubhayakar Savita, Quinn John G, Fairbrother Wayne J, Jones Robert, Gould Stephen E, Vucic Domagoj

机构信息

Departments of In Vivo Pharmacology, Genentech, South San Francisco, CA, 94110, USA.

Immunology Discovery, Genentech, South San Francisco, CA, 94110, USA.

出版信息

Cell Death Dis. 2022 Sep 28;13(9):831. doi: 10.1038/s41419-022-05283-w.

DOI:10.1038/s41419-022-05283-w
PMID:36171193
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9519744/
Abstract
摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21b2/9519744/d2538f9725f5/41419_2022_5283_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21b2/9519744/d2538f9725f5/41419_2022_5283_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21b2/9519744/d2538f9725f5/41419_2022_5283_Fig1_HTML.jpg

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IAP antagonist GDC-0917 is more potent than Debio1143 in promoting cell death, c-IAP1 degradation and tumor growth inhibition.IAP拮抗剂GDC-0917在促进细胞死亡、c-IAP1降解和抑制肿瘤生长方面比Debio1143更有效。
Cell Death Dis. 2022 Sep 28;13(9):831. doi: 10.1038/s41419-022-05283-w.
2
Antagonism of c-IAP and XIAP proteins is required for efficient induction of cell death by small-molecule IAP antagonists.小分子IAP拮抗剂有效诱导细胞死亡需要c-IAP和XIAP蛋白的拮抗作用。
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Ubiquitin binding modulates IAP antagonist-stimulated proteasomal degradation of c-IAP1 and c-IAP2(1).泛素结合调节IAP拮抗剂刺激的c-IAP1和c-IAP2的蛋白酶体降解(1)。
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Enhanced cytoprotective effects of the inhibitor of apoptosis protein cellular IAP1 through stabilization with TRAF2.通过与肿瘤坏死因子受体相关因子2(TRAF2)稳定结合增强凋亡抑制蛋白细胞IAP1的细胞保护作用。
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c-IAP1 cooperates with Myc by acting as a ubiquitin ligase for Mad1.c-IAP1 通过作为 Mad1 的泛素连接酶与 Myc 协同作用。
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2
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Clin Transl Sci. 2022 Jan;15(1):55-62. doi: 10.1111/cts.13002. Epub 2021 Nov 11.
3
Debio 1143 and high-dose cisplatin chemoradiotherapy in high-risk locoregionally advanced squamous cell carcinoma of the head and neck: a double-blind, multicentre, randomised, phase 2 study.
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Lancet Oncol. 2020 Sep;21(9):1173-1187. doi: 10.1016/S1470-2045(20)30327-2. Epub 2020 Aug 3.
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Statistical Fragility of Surgical and Procedural Clinical Trials in Orthopaedic Oncology.骨肿瘤外科学术和操作临床试验的统计学脆弱性。
J Am Acad Orthop Surg Glob Res Rev. 2020 Jun 1;4(6). doi: 10.5435/JAAOSGlobal-D-19-00152. eCollection 2020 Jun.
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Future Therapeutic Directions for Smac-Mimetics.Smac 模拟物的未来治疗方向。
Cells. 2020 Feb 11;9(2):406. doi: 10.3390/cells9020406.
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DEBIO 1143, an IAP inhibitor, reverses carboplatin resistance in ovarian cancer cells and triggers apoptotic or necroptotic cell death.DEBIO 1143,一种 IAP 抑制剂,可逆转卵巢癌细胞对卡铂的耐药性,并触发细胞凋亡或坏死性细胞死亡。
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