HB007
目录号 : GC63002HB007 是一种小的泛素相关修饰剂 1 (SUMO1) 降解剂。HB007 诱导 SUMO1 的泛素化和降解,导致体内肿瘤生长减少。HB007 可用于脑癌、乳腺癌、结肠癌和肺癌的研究。
Cas No.:2387821-46-5
Sample solution is provided at 25 µL, 10mM.
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HB007 is a small ubiquitin-related modifier 1 (SUMO1) degrader. HB007 induces ubiquitination and degradation of SUMO1, resulting in reduced tumor growth in vivo. HB007 can be used for the research of brain, breast, colon, and lung cancers[1][2].
HB007 (compound 24) (0.1-100 μM) inhibits LN229 cell growth in a concentration-dependent manner t[1].HB007 (10-25 μM) reduces SUM01 conjugation and total protein levels of SUM01 but not SUM02/3 or UB in LN229 cells t[1].
HB007 (compound 24) (25-50 mg/kg; i.p. for 15 d) significantly suppresses tumor growth of colon and lung cancer but had no effect on the body weights of mice[1].
[1]. Bellail AC, et, al. Ubiquitination and degradation of SUMO1 by small-molecule degraders extends survival of mice with patient-derived tumors. Sci Transl Med. 2021 Oct 13;13(615):eabh1486.
[2]. BELLAIL A, et, al. Compositions and methods for treating cancer. WO2019217509A1.
Cas No. | 2387821-46-5 | SDF | |
分子式 | C15H9ClN4OS | 分子量 | 328.78 |
溶解度 | 储存条件 | ||
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1 mg | 5 mg | 10 mg | |
1 mM | 3.0415 mL | 15.2077 mL | 30.4155 mL |
5 mM | 0.6083 mL | 3.0415 mL | 6.0831 mL |
10 mM | 0.3042 mL | 1.5208 mL | 3.0415 mL |
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Ubiquitination and degradation of SUMO1 by small-molecule degraders extends survival of mice with patient-derived tumors
Sci Transl Med 2021 Oct 13;13(615):eabh1486.PMID:34644148DOI:10.1126/scitranslmed.abh1486.
Discovery of small-molecule degraders that activate ubiquitin ligase–mediated ubiquitination and degradation of targeted oncoproteins in cancer cells has been an elusive therapeutic strategy. Here, we report a cancer cell–based drug screen of the NCI drug-like compounds library that enabled identification of small-molecule degraders of the small ubiquitin-related modifier 1 (SUMO1). Structure-activity relationship studies of analogs of the hit compound CPD1 led to identification of a lead compound HB007 with improved properties and anticancer potency in vitro and in vivo. A genome-scale CRISPR-Cas9 knockout screen identified the substrate receptor F-box protein 42 (FBXO42) of cullin 1 (CUL1) E3 ubiquitin ligase as required for HB007 activity. Using HB007 pull-down proteomics assays, we pinpointed HB007’s binding protein as the cytoplasmic activation/proliferation-associated protein 1 (CAPRIN1). Biolayer interferometry and compound competitive immunoblot assays confirmed the selectivity of HB007’s binding to CAPRIN1. When bound to CAPRIN1, HB007 induced the interaction of CAPRIN1 with FBXO42. FBXO42 then recruited SUMO1 to the CAPRIN1-CUL1-FBXO42 ubiquitin ligase complex, where SUMO1 was ubiquitinated in several of human cancer cells. HB007 selectively degraded SUMO1 in patient tumor–derived xenografts implanted into mice. Systemic administration of HB007 inhibited the progression of patient-derived brain, breast, colon, and lung cancers in mice and increased survival of the animals. This cancer cell–based screening approach enabled discovery of a small-molecule degrader of SUMO1 and may be useful for identifying other small-molecule degraders of oncoproteins.