HSP27 inhibitor J2 (J2) is an inhibitor of HSP27, which significantly induces abnormal HSP27 dimer formation and inhibits HSP27 macropolymer production[1-3].
HSP27 inhibitor J2 (J2) is an inhibitor of HSP27, which significantly induces abnormal HSP27 dimer formation and inhibits HSP27 macropolymer production[1-3].
J2(10 μM J2;12 hr)showed stronger HSP27 cross linking activity in HSP27 high expressed lung cancer cells and relatively low cytoxicity[4].
J2(15 mg/kg; i.p; on every other day after irradiation for 14d) treatment significantly inhibited immune cell infiltration in lung tissue. J2-treated mice reversed radiation-induced respiratory distress. J2 inhibited IR-induced lung fibrosis in mice[5-6].
HSP27抑制剂J2 (J2)是HSP27的抑制剂,能显著诱导异常HSP27二聚体形成,抑制HSP27大聚合物的生成[1-3]。
J2在高表达HSP27的肺癌细胞中表现出较强的HSP27交联活性,并且细胞毒性相对较低[4]。
J2(15 mg/kg; i.p; on every other day after irradiation for 14d)显著抑制肺组织免疫细胞浸润。j2治疗小鼠逆转了辐射引起的呼吸窘迫。J2抑制IR诱导的小鼠肺纤维化[5-6]。
参考文献:
[1]. Hwang SY, Kwak SY, et,al. Synthesis and biological effect of chrom-4-one derivatives as functional inhibitors of heat shock protein 27. Eur J Med Chem. 2017 Oct 20;139:892-900. doi: 10.1016/j.ejmech.2017.08.065. Epub 2017 Sep 1. PMID: 28869891.
[2]. Garrido C, Bruey JM, et,al. HSP27 inhibits cytochrome c-dependent activation of procaspase-9. FASEB J. 1999 Nov;13(14):2061-70. doi: 10.1096/fasebj.13.14.2061. PMID: 10544189.
[3]. Younghwa Na, et al. Methods for treating pulmonary fibrosis using chromenone derivatives.
[4]. Choi B, Choi SK, et,al. Sensitization of lung cancer cells by altered dimerization of HSP27. Oncotarget. 2017 Oct 31;8(62):105372-105382. doi: 10.18632/oncotarget.22192. PMID: 29285257; PMCID: PMC5739644.
[5]. Kim JY, An YM, et,al. HSP27 inhibitor attenuates radiation-induced pulmonary inflammation. Sci Rep. 2018 Mar 8;8(1):4189. doi: 10.1038/s41598-018-22635-9. PMID: 29520071; PMCID: PMC5843649.
[6]. Kim JY, Jeon S, et,al. The Hsp27-Mediated IkBα-NFκB Signaling Axis Promotes Radiation-Induced Lung Fibrosis. Clin Cancer Res. 2019 Sep 1;25(17):5364-5375. doi: 10.1158/1078-0432.CCR-18-3900. Epub 2019 May 24. PMID: 31126962.
| Cell experiment [1]: | |
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Cell lines |
NCI-H460 cells |
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Preparation Method |
Cells were treated with J2 at 10 μM for 12 hr. |
|
Reaction Conditions |
10 μM J2;12 hr |
|
Applications |
J2 showed stronger HSP27 cross linking activity in HSP27 high expressed lung cancer cells. |
| Animal experiment [2]: | |
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Animal models |
Male C57BL/6 mice |
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Preparation Method |
Mice were exposed to a single dose of 75 Gy delivered to the left lung in a single fraction,15 mg/kg of J2 was intraperitoneal administered on every other day after irradiation. |
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Dosage form |
15 mg/kg; i.p; every other day after irradiation for 14d. |
|
Applications |
J2 treatment significantly inhibited immune cell infiltration in lung tissue. |
|
参考文献: [1]. Choi B, Choi SK, et,al. Sensitization of lung cancer cells by altered dimerization of HSP27. Oncotarget. 2017 Oct 31;8(62):105372-105382. doi: 10.18632/oncotarget.22192. PMID: 29285257; PMCID: PMC5739644. |
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