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1

项与 Synovel Laboratory LLC 相关的药物

HB-007

靶点

SUMO1

作用机制

SUMO1抑制剂

在研机构-

原研机构

Synovel Laboratory LLC

[+3]

在研适应症-

非在研适应症

中枢神经系统肿瘤

最高研发阶段无进展

首次获批国家/地区-

首次获批日期-

100 项与 Synovel Laboratory LLC 相关的临床结果

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0 项与 Synovel Laboratory LLC 相关的专利（医药）

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2

项与 Synovel Laboratory LLC 相关的文献（医药）

2023-09-01·Molecular carcinogenesis

SUMO1 degrader induces ER stress and ROS accumulation through deSUMOylation of TCF4 and inhibition of its transcription of StarD7 in colon cancer.

Article

作者: Liu, Sheng ; Wang, Quan ; Jin, Hong Ri ; Jung, Sung Han ; Lo, Ho-Yin ; Bellail, Anita C ; Kim, Daeho ; Hao, Chunhai ; Zhao, Yin Quan ; Fu, Xue Qi ; Wan, Jun

Small molecule degraders of small ubiquitin-related modifier 1 (SUMO1) induce SUMO1 degradation in colon cancer cells and inhibits the cancer cell growth; however, it is unclear how SUMO1 degradation leads to the anticancer activity of the degraders. Genome-wide CRISPR-Cas9 knockout screen has identified StAR-related lipid transfer domain containing 7 (StarD7) as a critical gene for the degrader's anticancer activity. Here, we show that both StarD7 mRNA and protein are overexpressed in human colon cancer and its knockout significantly reduces colon cancer cell growth and xenograft progression. The treatment with the SUMO1 degrader lead compound HB007 reduces StarD7 mRNA and protein levels and increases endoplasmic reticulum (ER) stress and reactive oxygen species (ROS) production in colon cancer cells and three-dimensional (3D) organoids. The study further provides a novel mechanism of the compound anticancer activity that SUMO1 degrader-induced decrease of StarD7 occur through degradation of SUMO1, deSUMOylation and degradation of T cell-specific transcription 4 (TCF4) and thereby inhibition of its transcription of StarD7 in colon cancer cells, 3D organoids and patient-derived xenografts (PDX).

2021-10-13·Science Translational Medicine1区 · 医学

Ubiquitination and degradation of SUMO1 by small-molecule degraders extends survival of mice with patient-derived tumors

1区 · 医学

Article

作者: Higgins, Ryan K. ; Mosley, Amber L. ; Lo, Ho-Yin ; Hauck, Paula M. ; Wijeratne, Aruna B. ; Hao, Chunhai ; Hamdouchi, Chafiq ; Jiang, Wen ; Blanck, Maximilian ; Jung, Sung Han ; le Sage, Carlos ; Li, Jing ; Kim, Daeho ; Bellail, Anita C. ; Jin, Hong Ri ; Zhao, Yin Quan ; Shekhar, Anantha ; Ghosh, Manali ; Cross, Benedict C.S.

Small-molecule degraders of SUMO1 induce its ubiquitination and degradation through binding of CAPRIN1 in tumor cells in vitro and in vivo.

100 项与 Synovel Laboratory LLC 相关的药物交易

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100 项与 Synovel Laboratory LLC 相关的转化医学

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