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Experimental study of the anti-hyperuricemic effect of compound CC18013
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Xue-chen LI1, Nan JIANG1, Ya-jun YANG2, Zhen-xin YAN1, Lu ZHANG2, Dong-ting CHEN1, Jin-ying TIAN1, Zhi-yan XIAO2, Fei YE1
Chinese Journal of New Drugs | 2021, 30(16) : 1460 - 1465
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Chinese Journal of New Drugs | 2021, 30(16): 1460-1465
Experimental study of the anti-hyperuricemic effect of compound CC18013
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Xue-chen LI1, Nan JIANG1, Ya-jun YANG2, Zhen-xin YAN1, Lu ZHANG2, Dong-ting CHEN1, Jin-ying TIAN1, Zhi-yan XIAO2, Fei YE1
Affiliations
  • 1Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study, Beijing 100050, China
  • 2Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing Key Laboratory of Active Substance Discovery and Druggability Evaluation, Beijing 100050, China
Published: 2021-08-30
Outline
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Objective:

To study the anti-hyperuricemic efficacy, assess the safety of compound CC18013, and explore its possible mechanism related to xanthine oxidase (XOD) inhibition.

Methods:

By establishing the acute and chronic hyperuricemic mice models and use of febuxostat as the positive control drug, the effect of CC18013 on serum uric acid levels was detected; the XOD inhibiting ability of CC18013 was determined using in vitro XOD model. The effect of CC18013 on serum and tissue XOD activity in hyperuricemic mice was measured. The interaction between CC18013 and XOD was analyzed by molecular-docking. The body weight change and general state of the mice were observe after a single dose treatment of CC18013.

Results:

CC18013 dose-dependently reduced serum uric acid levels in vivo, with the lowest effective dose of 0.5 mg·kg-1. Its IC50 value of XOD inhibition in vitro was 4.6 nmol·L-1. Moreover, it significantly inhibited XOD activity in liver and small intestine. Molecular-docking result indicated that it had a strong interaction with XOD. It showed no evident toxicity under the single dose of 500 mg·kg-1.

Conclusion:

CC18013 is an XOD inhibitor with strong anti-hyperuricemic effect and high safety.

hyperuricemia  /  uric acid  /  xanthine oxidase
李雪晨, 姜楠, 杨亚军, 闫祯昕, 张露, 陈冬婷, 田金英, 肖志艳, 叶菲. 化合物CC18013抗高尿酸血症作用的实验研究. 中国新药杂志, 2021 , 30 (16) : 1460 -1465 .
Xue-chen LI, Nan JIANG, Ya-jun YANG, Zhen-xin YAN, Lu ZHANG, Dong-ting CHEN, Jin-ying TIAN, Zhi-yan XIAO, Fei YE. Experimental study of the anti-hyperuricemic effect of compound CC18013[J]. Chinese Journal of New Drugs, 2021 , 30 (16) : 1460 -1465 .
Appendix
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Year 2021 volume 30 Issue 16
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Article Info
  • Online Date：2026-10-28
  • Published：2021-08-30
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History
  • Accepted：2021-06-11
Funding
Affiliations
    1Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study, Beijing 100050, China
    2Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing Key Laboratory of Active Substance Discovery and Druggability Evaluation, Beijing 100050, China
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表12种不同金属材料的力学参数
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Family		 属数
Number of
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Number of
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Percentage of
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鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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