Wang, Juan; Du, Tongde; Lu, Ya; Lv, Yan; Du, Yuxin; Wu, Jianzhong; Ma, Rong; Xu, Chenxin; Feng, Jifeng published the artcile< VLX1570 regulates the proliferation and apoptosis of human lung cancer cells through modulating ER stress and the AKT pathway>, Safety of 9-(6-Aminopyridin-3-yl)-1-(3-(trifluoromethyl)phenyl)benzo[h][1,6]naphthyridin-2(1H)-one, the main research area is AKT endoplasmic reticulum stress human lung cancer proliferation apoptosis; cell proliferation endoplasmic reticulum stress AKT pathway; AKT pathway; ER stress; VLX1570; apoptosis; lung cancer; proliferation.
The ubiquitin-proteasome system (UPS) possesses unique functions in tumorigenesis and has great potential for targeting tumors. The effectiveness of inhibitors targeting UPS in solid tumors remains to be studied. We screened a library of inhibitors targeting the ubiquitination system and found the highly potent, low-concentration inhibitor mol. VLX1570 that specifically killed lung cancer cells. VLX1570 is an inhibitor of deubiquitinating enzyme activity and has also shown potential for preclin. cancer treatment. We found that VLX1570 significantly inhibited lung cancer cells proliferation and colony formation. VLX1570 induced a G2/M cell cycle arrest by downregulating CDK1 and CyclinB1. Moreover, VLX1570 significantly promoted the mitochondrial-associated apoptosis. Mechanistically speaking, VLX1570 activated the PERK/IRE1/ATF6 pathway and induced ER stress in lung cancer cell lines. The inhibition of ER stress by tauroursodeoxycholic acid sodium or 4-phenylbutyric acid enhanced VLX1570-induced apoptosis. In addition, VLX1570 treatment led to the inactivation of Akt signalling and inhibited the proliferation of lung cancer cells by downregulating the Akt pathway. Moreover, combined treatment with VLX1570 and Afatinib or Gefitinib induced synergistic anti-lung cancer activity. Our present study demonstrated a novel therapy using VLX1570, which inhibited the proliferation and increased apoptosis in human lung cancer.
Journal of Cellular and Molecular Medicine published new progress about Activating transcription factor 6α Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 1223001-51-1 belongs to class naphthyridine, and the molecular formula is C24H15F3N4O, Safety of 9-(6-Aminopyridin-3-yl)-1-(3-(trifluoromethyl)phenyl)benzo[h][1,6]naphthyridin-2(1H)-one.
Referemce:
1,8-Naphthyridine – Wikipedia,
1,8-Naphthyridine | C8H6N2 – PubChem