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LL6, the most promising novel small molecule kinase inhibitor obtained, induced apoptosis and suppressed the colony-forming capacities of various drug-resistant NSCLC cell lines, suppressed NSCLC cell migration, suppressed NSCLC xenograft tumor growth and Lewis lung carcinoma allograft tumor metastasis in mice, and markedly reduced the number and burden of lung tumors in KrasG12D/+ transgenic mice, with low toxicity (54)

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For HIF transcription factors, this occurs by hydroxylation at conserved proline residues by prolyl hydroxylases under normoxia, allowing their recognition and ubiquitination by the VHL E3 ubiquitin ligase, which targets HIFs for proteasomal degradation