Citation
Li, Qing-Qing, et al. "Design, Synthesis, and Biological Evaluation of 3,4-Dihydroisoquinolin-1(2H)-one Derivatives as Protein Arginine Methyltransferase 5 Inhibitors for the Treatment of Non-Hodgkin's Lymphoma." Journal of Medicinal Chemistry, vol. 68, no. 1, 2025, pp. 108-134.
Li QQ, Quan X, Wang ZX, et al. Design, Synthesis, and Biological Evaluation of 3,4-Dihydroisoquinolin-1(2H)-one Derivatives as Protein Arginine Methyltransferase 5 Inhibitors for the Treatment of Non-Hodgkin's Lymphoma. J Med Chem. 2025;68(1):108-134.
Li, Q. Q., Quan, X., Wang, Z. X., Qiao, N., Ni, X. F., Jing, X. L., Zhou, S. S., Tian, X. L., Zheng, G. C., Zhan, K. N., Xu, Y. J., Yang, J., Zhou, Y., Liang, X. T., Zhao, Z. H., Wei, T. H., Liu, Q., Bai, M. Y., Sun, S. L., ... Shi, Z. H. (2025). Design, Synthesis, and Biological Evaluation of 3,4-Dihydroisoquinolin-1(2H)-one Derivatives as Protein Arginine Methyltransferase 5 Inhibitors for the Treatment of Non-Hodgkin's Lymphoma. Journal of Medicinal Chemistry, 68(1), 108-134. https://doi.org/10.1021/acs.jmedchem.4c01548
Li QQ, et al. Design, Synthesis, and Biological Evaluation of 3,4-Dihydroisoquinolin-1(2H)-one Derivatives as Protein Arginine Methyltransferase 5 Inhibitors for the Treatment of Non-Hodgkin's Lymphoma. J Med Chem. 2025 01 9;68(1):108-134. PubMed PMID: 39722476.
TY - JOUR
T1 - Design, Synthesis, and Biological Evaluation of 3,4-Dihydroisoquinolin-1(2H)-one Derivatives as Protein Arginine Methyltransferase 5 Inhibitors for the Treatment of Non-Hodgkin's Lymphoma.
AU - Li,Qing-Qing,
AU - Quan,Xu,
AU - Wang,Zi-Xuan,
AU - Qiao,Nuo,
AU - Ni,Xing-Feng,
AU - Jing,Xiao-Long,
AU - Zhou,Shuang-Shuang,
AU - Tian,Xin-Lei,
AU - Zheng,Guo-Chuang,
AU - Zhan,Kang-Ning,
AU - Xu,Yu-Jing,
AU - Yang,Jin,
AU - Zhou,Yun,
AU - Liang,Xiao-Ting,
AU - Zhao,Zong-Hao,
AU - Wei,Tian-Hua,
AU - Liu,Qian,
AU - Bai,Ming-Yu,
AU - Sun,Shan-Liang,
AU - Yu,Yan-Cheng,
AU - Cao,Peng,
AU - Li,Nian-Guang,
AU - Zhang,Xiao-Meng,
AU - Liu,Jian,
AU - Shi,Zhi-Hao,
Y1 - 2024/12/26/
PY - 2025/1/9/medline
PY - 2024/12/26/pubmed
PY - 2024/12/26/entrez
SP - 108
EP - 134
JF - Journal of medicinal chemistry
JO - J Med Chem
VL - 68
IS - 1
N2 - Through catalyzing the transfer of methyl groups onto the guanidinium of arginine, protein arginine methyltransferase 5 (PRMT5) was essential to the cell growth of cancer cells. By utilizing a scaffold hopping strategy, a novel series of 3,4-dihydroisoquinolin-1(2H)-one derivatives were designed and synthesized. Through a systematic SAR study, D3 demonstrated excellent PRMT5 inhibitory activity, potent antiproliferative activity against Z-138, favorable pharmacokinetic profiles, and low hERG toxicity. Molecular docking, molecular dynamic (MD) simulation, and surface plasmon resonance (SPR) study indicated that D3 was tightly interacted with PRMT5. Meanwhile, D3 exhibited high selectivity against PRMT5, which could inhibit the growth of various cancer cells, induce apoptosis, and arrest the cell cycle in the G0/G1 phase. Additionally, D3 possessed excellent antitumor efficacy in Z-138 xenograft models, low toxicity in vivo, and acceptable drug metabolism and pharmacokinetics (DMPK) profiles in vitro. Therefore, D3 can be developed as a promising candidate for the treatment of non-Hodgkin's lymphoma (NHL).
SN - 1520-4804
UR - https://www.unboundmedicine.com/medline/citation/39722476/
DB - PRIME
DP - Unbound Medicine
ER -
