我国自主开发的抗菌新药临床管线最新进展

杨信怡, 李聪然, 王秀坤, 郑忠辉, 孙培译, 许春杰, 陈鲁妮, 蒋建东, Staffan Normark, Birgitta Henriques-Normark, 游雪甫

工程（英文） ›› 2024, Vol. 38 ›› Issue (7) : 52-68.

PDF(1650 KB)
PDF(1650 KB)
工程（英文） ›› 2024, Vol. 38 ›› Issue (7) : 52-68. DOI: 10.1016/j.eng.2024.02.009
研究论文
Review

我国自主开发的抗菌新药临床管线最新进展

作者信息 +

An Update on the Clinical Pipelines of New Antibacterial Drugs Developed in China

Author information +
History +

摘要

抗生素耐药问题危及全球人类健康，需各国进一步采取切实行动。此背景下，最令人关注的一个问题是处于开发中的抗菌新药品种是否足够丰富。近期，尽管有多篇高质量综述发表，介绍了全球抗菌新药临床管线研究动态，但没有任何一篇文章系统关注过我国自主研发、处于临床研究阶段的抗菌药物品种。本文全面介绍了2019年以来我国新获准上市及临床评价阶段抗菌新药的最新进展。文中信息主要通过官网搜索、商业数据库查询、文献检索、人员咨询等方式获得。本文共介绍和更新了截至2023年6月30日，我国17家制药企业和开发机构的20个抗菌新药管线的研究进展。其中，两个属传统抗生素类别的新药分别于2019年和2021年经国家药监局批准上市，而18个临床开发阶段的管线中，一个处于上市申请阶段，5个处于III期临床，6个处于II期临床，6个处于I期临床。这些临床研究阶段的候选药物，多数属于传统抗生素母核的改构药或药物单组分，两个是双作用活性的杂合抗生素，一个是重组抗菌蛋白。总之，本文分析反映，我国临床开发阶段的抗菌管线虽有17个，但囿于多样性不足。藉此，希望我国制药企业和研究机构在未来的原创抗菌新药研发中，能推出更多市场前景良好、满足临床差异性需求的侯选药物品种。

Abstract

Antibacterial resistance is a global health threat that requires further concrete action on the part of all countries. In this context, one of the biggest concerns is whether enough new antibacterial drugs are being discovered and developed. Although several high-quality reviews on clinical antibacterial drug pipelines from a global perspective were published recently, none provides comprehensive information on original antibacterial drugs at clinical stages in China. In this review, we summarize the latest progress of novel antibacterial drugs approved for marketing and under clinical evaluation in China since 2019. Information was obtained by consulting official websites, searching commercial databases, retrieving literature, asking personnel from institutions or companies, and other means, and a considerable part of the data covered here has not been included in other reviews. As of June 30, 2023, a total of 20 antibacterial projects from 17 Chinese pharmaceutical companies or developers were identified and updated. Among them, two new antibacterial drugs that belong to traditional antibiotic classes were approved by the National Medical Products Administration (NMPA) in China in 2019 and 2021, respectively, and 18 antibacterial agents are in clinical development, with one under regulatory evaluation, five in phase-3, six in phase-2, and six in phase-1. Most of the clinical candidates are new analogs or mono-components of traditional antibacterial pharmacophore types, including two dual-acting hybrid antibiotics and a recombinant antibacterial protein. Overall, despite there being 17 antibacterial clinical candidates, our analysis indicates that there are still relatively few clinically differentiated antibacterial agents in stages of clinical development in China. Hopefully, Chinese pharmaceutical companies and institutions will develop more innovative and clinically differentiated candidates with good market potential in the future research and development (R&D) of original antibacterial drugs.

关键词

抗生素耐药 / 新抗生素 / 临床管线 / WHO“优先”病原体 / “重大新药创制”科技重大专项

Keywords

Antimicrobial resistance / New antibiotics / Clinical pipelines / WHO priority pathogens / National Mega-Project for Innovative Drugs

引用本文

EndNote

Ris (Procite)

Bibtex

导出引用
杨信怡, 李聪然, 王秀坤. 我国自主开发的抗菌新药临床管线最新进展. Engineering. 2024, 38(7): 52-68 https://doi.org/10.1016/j.eng.2024.02.009

参考文献

原文顺序 | 文献年度倒序 | 文中引用次数倒序
[1]
C.J.L. Murray, K.S. Ikuta, F. Sharara, L. Swetschinski, G. Robles Aguilar, A. Gray, et al.Antimicrobial Resistance Collaborators. Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. Lancet, 399 (10325) (2022), pp. 629-655
[2]
U.S. Mission Geneva. Antimicrobial resistance—no action today, no cure tomorrow [Internet]. Geneva: US Mission Geneva; 2011 Apr 5 [cited 2023 Jun 27]. Available from: https://geneva.usmission.gov/2011/04/05/antimicrobial-resistance-no-action-today-no-cure-tomorrow/#:∼:text=Anti-microbial%20resistance%20%E2%80%93%20or%20AR%20%E2%80%93%20is%20the,Cure%20Tomorrow%E2%80%9D%20to%20focus%20attention%20on%20the%20issue.
[3]
WHO. Lack of new antibiotics threatens global efforts to contain drug-resistant infections [Internet]. Geneva: WHO; 2020 Jan 17 [cited 2023 Jun 27]. Available from: https://www.who.int/news/item/17-01-2020-lack-of-new-antibiotics-threatens-global-efforts-to-contain-drug-resistant-infections.
[4]
WHO. WHO publishes list of bacteria for which new antibiotics are urgently needed [Internet]. Geneva: WHO; 2017 Feb 27 [cited 2023 Jun 27]. Available from: https://www.who.int/news/item/27-02-2017-who-publishes-list-of-bacteria-for-which-new-antibiotics-are-urgently-needed.
[5]
V.A. Dartois, E.J. Rubin. Anti-tuberculosis treatment strategies and drug development: challenges and priorities. Nat Rev Microbiol, 20 (11) (2022), pp. 685-701
[6]
U. Theuretzbacher, S. Gottwalt, P. Beyer, M. Butler, L. Czaplewski, C. Lienhardt, et al. Analysis of the clinical antibacterial and antituberculosis pipeline. Lancet Infect Dis, 19 (2) (2019), pp. e40-e50
[7]
M.S. Butler, V. Gigante, H. Sati, S. Paulin, L. Al-Sulaiman, J.H. Rex, et al. Analysis of the clinical pipeline of treatments for drug-resistant bacterial infections: despite progress, more action is needed. Antimicrob Agents Chemother, 66 (3) (2022), p. e0199121
[8]
U. Theuretzbacher, K. Bush, S. Harbarth, M. Paul, J.H. Rex, E. Tacconelli, et al. Critical analysis of antibacterial agents in clinical development. Nat Rev Microbiol, 18 (5) (2020), pp. 286-298
[9]
U. Theuretzbacher, K. Outterson, A. Engel, A. Karlén. The global preclinical antibacterial pipeline. Nat Rev Microbiol, 18 (5) (2020), pp. 275-285
[10]
M. Miethke, M. Pieroni, T. Weber, M. Brönstrup, P. Hammann, L. Halby, et al. Towards the sustainable discovery and development of new antibiotics. Nat Rev Chem, 5 (10) (2021), pp. 726-749
[11]
X. Zhen, C. Stålsby Lundborg, X. Sun, N. Zhu, S. Gu, H. Dong. Economic burden of antibiotic resistance in China: a national level estimate for inpatients. Antimicrob Resist Infect Control, 10 (1) (2021), p. 5
[12]
Q. Long, L. Guo, W. Jiang, S. Huan, S. Tang. Ending tuberculosis in China: health system challenges. Lancet Public Health, 6 (12) (2021), pp. e948-e953
[13]
The State Council, People’s Republic of China. The national medium- and long-term program for science and technology development (2006-2020)—an outline [Internet]. Beijing: the State Council, People’s Republic of China; [cited 2023 Jun 27]. Available from: https://www.itu.int/en/ITU-D/Cybersecurity/Documents/National_Strategies_Repository/China_2006.pdf.
[14]
Ministry of Science and Technology, People’s Republic of China. The major science and technology project of “major new drug creation” press conference [Internet]. Beijing: Ministry of Science and Technology, People’s Republic of China; 2019 Jul 31 [cited 2023 Jun 27]. Available from: https://www.most.gov.cn/xwzx/twzb/fbh19073101/.
[15]
People’s Daily Online. The major science and technology project of “major new drug creation” ended [Internet]. Beijing: People’s Daily Online; 2021 Feb 2 [cited 2023 Jun 27]. Available from: https://www.gov.cn/xinwen/2021-02/02/content_5584285.htm.
[16]
H. Hu, X. Lu, H. Xu, L. Zhou. Analysis of new drug registration and review in China in 2021. Acta Pharm Sin B, 12 (4) (2022), pp. 2127-2128
[17]
WHO. 2021 antibacterial agents in clinical and preclinical development: an overview and analysis [Internet]. Geneva: WHO; 2022 May 27 [cited 2023 Jun 27]. Available from: https://www.who.int/publications/i/item/9789240047655.
[18]
J. Dai, Y. Wang, J. Liu, W. He. The regulatory genes involved in spiramycin and bitespiramycin biosynthesis. Microbiol Res., 240 (2020), p. 126532
[19]
B. Bozdogan, P.C. Appelbaum. Oxazolidinones: activity, mode of action, and mechanism of resistance. Int J Antimicrob Agents, 23 (2) (2004), pp. 113-119
[20]
T. Hao, W. He. Advances in metabolic engineering of macrolide antibiotics. Chin J Biotechnol, 37 (5) (2021), pp. 1737-1747
[21]
X. Cao, X. Du, H. Jiao, Q. An, R. Chen, P. Fang, et al. Carbohydrate-based drugs launched during 2000-2021. Acta Pharm Sin B, 12 (10) (2022), pp. 3783-3821
[22]
H. Yan, J. Sun, K. Wang, H. Wang, S. Wu, L. Bao, et al. Repurposing carrimycin as an antiviral agent against human coronaviruses, including the currently pandemic SARS-CoV-2. Acta Pharm Sin B, 11 (9) (2021), pp. 2850-2858
[23]
Beijing YouAn Hospital. The clinical study of carrimycin on treatment patients with COVID-19 [Internet]. Beijing: Beijing YouAn Hospital; 2020 Feb 27 [cited 2023 Jun 27]. Available from: https://www.clinicaltrials.gov/ct2/show/NCT04286503.
[24]
W. Wang, K.M. Voss, J. Liu, M.F. Gordeev. Nonclinical evaluation of antibacterial oxazolidinones contezolid and contezolid acefosamil with low serotonergic neurotoxicity. Chem Res Toxicol, 34 (5) (2021), pp. 1348-1354
[25]
S.M. Hoy. Contezolid: first approval. Drugs, 81 (13) (2021), pp. 1587-1591
[26]
H. Yuan, H. Wu, Y. Zhang, H. Huang, Y. Li, J. Wu, et al. Clinical pharmacology and utility of contezolid in Chinese patients with complicated skin and soft-tissue infections. Antimicrob Agents Chemother, 66 (6) (2022), p. e0243021
[27]
X. Zhao, H. Huang, H. Yuan, Z. Yuan, Y. Zhang. A phase III multicentre, randomized, double-blind trial to evaluate the efficacy and safety of oral contezolid versus linezolid in adults with complicated skin and soft tissue infections. J Antimicrob Chemother, 77 (6) (2022), pp. 1762-1769
[28]
MicuRx. Pipeline development: build global competitiveness in the field of anti-infection [Internet]. Shanghai: MicuRx; [cited 2023 Jun 27]. Available from: http://www.micurxchina.com/r-d-pipeline.
[29]
M. Yang, S. Zhan, L. Fu, Y. Wang, P. Zhang, G. Deng. Prospects of contezolid (MRX-I) against multidrug-resistant tuberculosis and extensively drug-resistant tuberculosis. Drug Discov Ther, 16 (2) (2022), pp. 99-101
[30]
C. Shoen, M. DeStefano, B. Hafkin, M. Cynamon. In vitro and in vivo activities of contezolid (MRX-I) against Mycobacterium tuberculosis. Antimicrob Agents Chemother, 62 (8) (2018), p. 62
[31]
X.Y. Yang, C.R. Li, R.H. Lou, Y.M. Wang, W.X. Zhang, H.Z. Chen, et al. In vitro activity of recombinant lysostaphin against Staphylococcus aureus isolates from hospitals in Beijing, China. J Med Microbiol, 56 (Pt 1) (2007), pp. 71-76
[32]
Z. Ma, A.S. Lynch. Development of a dual-acting antibacterial agent (TNP-2092) for the treatment of persistent bacterial infections. J Med Chem, 59 (14) (2016), pp. 6645-6657
[33]
Y. Li, M. Yan, F. Xue, W. Zhong, X. Liu, X. Chen, et al. In vitro and in vivo activities of a novel β-lactamase inhibitor combination imipenem/XNW 4107 against recent clinical Gram-negative bacilli from China. J Glob Antimicrob Resist, 31 (2022), pp. 1-9
[34]
X.W. Ji, F. Xue, Z.S. Kang, W. Zhong, I.H. Kuan, X.P. Yang, et al. Model-informed drug development, pharmacokinetic/pharmacodynamic cutoff value determination, and antibacterial efficacy of benapenem against Enterobacteriaceae. Antimicrob Agents Chemother, 64 (3) (2020), p. 64
[35]
Z. Ma, S. He, Y. Yuan, Z. Zhuang, Y. Liu, H. Wang, et al. Design, synthesis, and characterization of TNP-2198, a dual-targeted rifamycin-nitroimidazole conjugate with potent activity against microaerophilic and anaerobic bacterial pathogens. J Med Chem, 65 (6) (2022), pp. 4481-4495
[36]
Hu BY D Z, Huang ZG, Lin RB, Xiao ML, Xie JS, et al., inventors; QiLu Pharmaceutical, assignee. A new β-lactamase inhibitor. China patent CN109311881B. 2021 Jul 13.
[37]
A. Asadi, M. Abdi, E. Kouhsari, P. Panahi, M. Sholeh, N. Sadeghifard, et al. Minocycline, focus on mechanisms of resistance, antibacterial activity, and clinical effectiveness: back to the future. J Glob Antimicrob Resist, 22 (2020), pp. 161-174
[38]
S.C. Nang, M.A.K. Azad, T. Velkov, Q.T. Zhou, J. Li. Rescuing the last-line polymyxins: achievements and challenges. Pharmacol Rev, 73 (2) (2021), pp. 679-728
[39]
N. Kohira, J. West, A. Ito, T. Ito-Horiyama, R. Nakamura, T. Sato, et al. In vitro antimicrobial activity of a siderophore cephalosporin, S-649266, against Enterobacteriaceae clinical isolates, including carbapenem-resistant strains. Antimicrob Agents Chemother, 60 (2) (2015), pp. 729-734
[40]
M.V. Worley, S.J. Estrada. Bedaquiline: a novel antitubercular agent for the treatment of multidrug-resistant tuberculosis. Pharmacotherapy, 34 (11) (2014), pp. 1187-1197
[41]
N. Riccardi, A. Giacomelli, D. Canetti, A. Comelli, E. Intini, G. Gaiera, et al. Clofazimine: an old drug for never-ending diseases. Future Microbiol, 15 (7) (2020), pp. 557-566
[42]
S. Khoshnood, E. Taki, N. Sadeghifard, V.H. Kaviar, M.H. Haddadi, Z. Farshadzadeh, et al. Mechanism of action, resistance, synergism, and clinical implications of delamanid against multidrug-resistant Mycobacterium tuberculosis. Front Microbiol, 12 (2021), p. 717045
[43]
M.D. Bastos, B.G. Coutinho, M.L. Coelho. Lysostaphin: a staphylococcal bacteriolysin with potential clinical applications. Pharmaceuticals, 3 (4) (2010), pp. 1139-1161
[44]
Shanghai Hi-tech Bioengineering Co., Ltd. Introduction to biotype skin and mucosal disinfectants [Internet]. Shanghai: Shanghai Hi-tech Bioengineering Co., Ltd.; [cited 2023 Jun 27]. Available from: http://www.hi-tech-bio.com/product/46/.
[45]
R. Domalaon, T. Idowu, G.G. Zhanel, F. Schweizer. Antibiotic hybrids: the next generation of agents and adjuvants against Gram-negative pathogens?. Clin Microbiol Rev, 31 (2) (2018), p. 31
[46]
A.S. Surur, D. Sun. Macrocycle-antibiotic hybrids: a path to clinical candidates. Front Chem, 9 (2021), p. 659845
[47]
C.R. Fisher, S.M. Schmidt-Malan, Z. Ma, Y. Yuan, S. He, R. Patel. In vitro activity of TNP-2092 against periprosthetic joint infection-associated Staphylococci. Diagn Microbiol Infect Dis, 97 (3) (2020), p. 115040
[48]
G.T. Robertson, E.J. Bonventre, T.B. Doyle, Q. Du, L. Duncan, T.W. Morris, et al. In vitro evaluation of CBR-2092, a novel rifamycin-quinolone hybrid antibiotic: microbiology profiling studies with Staphylococci and Streptococci. Antimicrob Agents Chemother, 52 (7) (2008), pp. 2324-2334
[49]
TenNor Therapeutics. TNP-2092 IV: medical device associated bacterial biofilm infections [Internet]. Suzhou: TenNor Therapeutics; 2021 Dec 24 [cited 2023 Jun 27]. Available from: http://www.tennorx.com/cn/NewsD.html?id=389&page=3&type=1.
[50]
TenNor Therapeutics. Clinical studies on the intra-articular local administration of TenNor Therapeutics’ TNP-2092 for prosthetic joint infections start [Internet]. Suzhou: TenNor Therapeutics; 2023 Sep 15 [cited 2024 Mar 11]. Available from: http://www.tennorx.com/cn/NewsD.html?id=455&page=1&type=1.
[51]
A. Nazli, D.L. He, H. Xu, Z.P. Wang, Y. He. A comparative insight on the newly emerging rifamycins: rifametane, rifalazil, TNP- 2092 and TNP-2198. Curr Med Chem, 29 (16) (2022), pp. 2846-2862
[52]
TenNor Therapeutics. Rifasutenizole for H. pylori received FDA QIDP designation [Internet]. Suzhou: TenNor Therapeutics; 2023 Apr 13 [cited 2023 Jun 27]. Available from: http://www.tennorx.com/cn/NewsD.html?id=376&page=1&type=1.
[53]
F. Bouchet, H. Atze, M. Fonvielle, Z. Edoo, M. Arthur, M. Ethève-Quelquejeu, et al. Diazabicyclooctane functionalization for inhibition of β-lactamases from Enterobacteria. J Med Chem, 63 (10) (2020), pp. 5257-5273
[54]
K. Bush, P.A. Bradford. β-lactams and β-lactamase inhibitors: an overview. Cold Spring Harb Perspect Med, 6 (8) (2016), p. 6
[55]
db.yaozh.com [Internet]. Clinical trials in China. Chongqing: db.yaozh.com; [cited 2023 Jun 27]. Available from: https://db.yaozh.com/linchuangshiyan?comprehensivesearchcontent=%E8%82%BE%E7%82%8E.
[56]
Guangdong Jincheng Jinsu Pharmaceutical Co., Ltd. Jincheng Jinsu’s litazolid (LT-01) dry suspension project completed its phase I clinical trial [Internet]. Zhongshan: Guangdong Jincheng Jinsu Pharmaceutical Co., Ltd.; 2022 Nov 17 [cited 2023 Jun 27]. Available from: http://www.gdjcjs.com/newsInfo?newsid=25.
[57]
L. Jin, S. Yao, L. Yin, M. Xu, C. Hu. Crystal structure characteristics of litazolidone. Chin J Antibiot, 46 (8) (2021), pp. 766-772
[58]
F. Qu, J. Zhang, H. Wang, C. Zhang, T. Jia, Y. Yuan, et al. In vitro antimicrobial activity of litazolid. Chin J Antibiot, 41 (12) (2016), pp. 942-949
[59]
Z. Zhu, Z. Chen, L. Lang, H. Wang, Y. Li, Q. Wang, et al. In vivo antibacterial activity of litazolid dry suspension. Chin J Antibiot, 43 (2) (2018), pp. 249-254
[60]
Guangdong Jincheng Jinsu Pharmaceutical Co., Ltd. Jincheng Jinsu Pharmaceutical: announcement on the ethical review approval of phase II clinical trials for litazolid dry suspension (LT-01) project [Internet]. Zhongshan: Guangdong Jincheng Jinsu Pharmaceutical Co., Ltd.; 2023 Apr 18 [cited 2023 Jun 27]. Available from: https://finance.eastmoney.com/a/202304182695073310.html.
[61]
M.D. Huband, J.D. Thompson, N.D. Gurung, Q. Liu, L. Li, J. Zhang, et al. Activity of the novel aminomethylcycline KBP-7072 and comparators against 1057 geographically diverse recent clinical isolates from the SENTRY surveillance program, 2019. Antimicrob Agents Chemother, 66 (1) (2022), p. e0139721
[62]
M.D. Huband, R.E. Mendes, M.A. Pfaller, J.M. Lindley, G.J. Strand, V.J. Benn, et al. In vitro activity of KBP-7072, a novel third-generation tetracycline, against 531 recent geographically diverse and molecularly characterized Acinetobacter baumannii species complex isolates. Antimicrob Agents Chemother, 64 (5) (2020), p. 64
[63]
R. Han, L. Ding, Y. Yang, Y. Guo, D. Yin, S. Wu, et al. In vitro activity of KBP-7072 against 536 Acinetobacter baumannii complex isolates collected in China. Microbiol Spectr, 10 (1) (2022), p. e0147121
[64]
F. Yang, Y. Wang, P. Wang, M. Hong, V. Benn. Multiple ascending dose safety, tolerability, and pharmacokinetics of KBP-7072, a novel third-generation tetracycline. Open Forum Infect Dis, 4 (suppl_1) (2017), p. S291
[65]
X. Tan, M. Zhang, Q. Liu, P. Wang, T. Zhou, Y. Zhu, et al. Nonclinical pharmacokinetics, protein binding, and elimination of KBP-7072, an aminomethylcycline antibiotic, in animal models. Antimicrob Agents Chemother, 64 (6) (2020), p. 64
[66]
China PhIRDA. U.S.. FDA grants Shandong Hengli’s KBP-7072 as QIDP and fast track designations [Internet]. Beijing: China PhIRDA; 2016 Nov 23 [cited 2023 Jun 27]. Available from: http://www.phirda.com/artilce_14355.html.
[67]
KBP Biosciences. KBP-7072 [Internet]. Singapore: KBP Bioscience; [cited 2023 Jun 27]. Available from: https://www.kbpbio.com/index.php?c=show&id=25.
[68]
S. Wu, D. Yin, P. Zhi, Y. Guo, Y. Yang, D. Zhu, et al. In vitro activity of MRX-8 and comparators against clinical isolated Gram-negative bacilli in China. Front Cell Infect Microbiol, 12 (2022), p. 829592
[69]
L.R. Duncan, W. Wang, H.S. Sader. In vitro potency and spectrum of the novel polymyxin MRX-8 tested against clinical isolates of Gram-negative bacteria. Antimicrob Agents Chemother, 66 (5) (2022), p. e0013922
[70]
A.J. Lepak, W. Wang, D.R. Andes. Pharmacodynamic evaluation of MRX-8, a novel polymyxin, in the neutropenic mouse thigh and lung infection models against Gram-negative pathogens. Antimicrob Agents Chemother, 64 (11) (2020), p. 64
[71]
A.T. Aslan, M. Akova, D.L. Paterson. Next-generation polymyxin class of antibiotics: a ray of hope illuminating a dark road. Antibiotics, 11 (12) (2022), p. 11
[72]
MicuRx. MicuRx Pharmaceuticals completed the first subject dosing of MRX-8 (a new drug against drug-resistant bacteria) in China [Internet]. Shanghai: MicuRx; 2022 Nov 19 [cited 2023 Jun 27]. Available from: https://www.micurx.com/1210.html#:∼:text=The%20ongoing%20Phase%201%20clinical%20trial%20in%20China,and%20is%20expected%20to%20be%20completed%20in%202023.
[73]
K. Bihan, Q. Lu, M. Enjalbert, M. Apparuit, O. Langeron, J.J. Rouby, et al. Determination of colistin and colistimethate levels in human plasma and urine by high-performance liquid chromatography-tandem mass spectrometry. Ther Drug Monit, 38 (6) (2016), pp. 796-803
[74]
Y. Kimura, H. Kitamura, K. Hayashi. A method for separating commercial colistin complex into new components: colistins pro-A, pro-B and pro-C. J Antibiot, 35 (11) (1982), pp. 1513-1520
[75]
J. Shoji, T. Kato, H. Hinoo. The structure of polymyxin S. (studies on antibiotics from the genus Bacillus. XXI). J Antibiot, 30 (12) (1977), pp. 1035-1041
[76]
A.L. Cui, X.X. Hu, Y. Gao, J. Jin, H. Yi, X.K. Wang, et al. Synthesis and bioactivity investigation of the individual components of cyclic lipopeptide antibiotics. J Med Chem, 61 (5) (2018), pp. 1845-1857
[77]
A.L. Cui, X.X. Hu, Y. Chen, J. Jin, H. Yi, X.K. Wang, et al. Design, synthesis, and bioactivity of cyclic lipopeptide antibiotics with varied polarity, hydrophobicity, and positive charge distribution. ACS Infect Dis, 6 (7) (2020), pp. 1796-1806
[78]
Jiangsu Aosaikang Pharmaceutical Co., Ltd. New drugs in development [Internet]. Nanjing: Jiangsu Aosaikang Pharmaceutical Co., Ltd.; [cited 2023 Jun 27]. Available from: https://www.ask-pharm.com/inside/4/87.html.
[79]
PharmaSources. Monthly news review of PharmaSources (February)—R&D [Internet]. Shanghai: PharmaSources; 2023 Mar 13 [cited 2023 Jun 27]. Available from: https://www.pharmasources.com/news/news-review-of-pharmasources-75993.html.
[80]
R. Mahajan. Bedaquiline: first FDA-approved tuberculosis drug in 40 years. Int J Appl Basic Med Res, 3 (1) (2013), pp. 1-2
[81]
Z. Huang, W. Luo, D. Xu, F. Guo, M. Yang, Y. Zhu, et al. Discovery and preclinical profile of sudapyridine (WX-081), a novel anti-tuberculosis agent. Bioorg Med Chem Lett, 71 (2022), p. 128824
[82]
R. Yao, B. Wang, L. Fu, L. Li, K. You, Y.G. Li, et al. Sudapyridine (WX-081), a novel compound against Mycobacterium tuberculosis. Microbiol Spectr, 10 (1) (2022), p. e0247721
[83]
H. Xiao, X. Yu, Y. Shang, R. Ren, Y. Xue, L. Dong, et al. In vitro and intracellular antibacterial activity of sudapyridine (WX-081) against tuberculosis. Infect Drug Resist, 16 (2023), pp. 217-224
[84]
R. Zhu, Y. Shang, S. Chen, H. Xiao, R. Ren, F. Wang, et al. In vitro activity of the sudapyridine (WX-081) against non-tuberculous mycobacteria isolated in Beijing, China. Microbiol Spectr, 10 (6) (2022), p. e0137222
[85]
Y. Lu, M. Zheng, B. Wang, L. Fu, W. Zhao, P. Li, et al. Clofazimine analogs with efficacy against experimental tuberculosis and reduced potential for accumulation. Antimicrob Agents Chemother, 55 (11) (2011), pp. 5185-5193
[86]
J.A.M. Stadler, G. Maartens, G. Meintjes, S. Wasserman. Clofazimine for the treatment of tuberculosis. Front Pharmacol, 14 (2023), p. 1100488
[87]
J. Xu, B. Wang, L. Fu, H. Zhu, S. Guo, H. Huang, et al. In vitro and in vivo activities of the riminophenazine TBI-166 against Mycobacterium tuberculosis. Antimicrob Agents Chemother, 63 (5) (2019), p. 63
[88]
Y. Zhang, H. Zhu, L. Fu, B. Wang, S. Guo, X. Chen, et al. Identifying regimens containing TBI-166, a new drug candidate against Mycobacterium tuberculosis in vitro and in vivo. Antimicrob Agents Chemother, 63 (7) (2019), p. 63
[89]
Y. Ding, H. Zhu, L. Fu, W. Zhang, B. Wang, S. Guo, et al. Superior efficacy of a TBI-166, bedaquiline, and pyrazinamide combination regimen in a murine model of tuberculosis. Antimicrob Agents Chemother, 66 (9) (2022), p. e0065822
[90]
B.D. Edwards, S.K. Field. The struggle to end a millennia-long pandemic: novel candidate and repurposed drugs for the treatment of tuberculosis. Drugs, 82 (18) (2022), pp. 1695-1715
[91]
TB Alliance, Institute of Materia Medica. TBI-223 [Internet]. New York City: The Working Group for New TB Drugs; [cited 2023 Jun 27]. Available from: https://www.newtbdrugs.org/pipeline/compound/tbi-223.
[92]
D.A. Negatu, W.W. Aragaw, J. Cangialosi, V. Dartois, T. Dick. Side-by-side profiling of oxazolidinones to estimate the therapeutic window against mycobacterial infections. Antimicrob Agents Chemother, 67 (4) (2023), p. e0165522
[93]
S.Y. Li, P.J. Converse, F. Betoudji, J. Lee, K. Mdluli, A. Upton, et al. Next-generation diarylquinolines improve sterilizing activity of regimens with pretomanid and the novel oxazolidinone TBI-223 in a mouse tuberculosis model. Antimicrob Agents Chemother, 67 (4) (2023), p. e0003523
[94]
W. Luo, Z. Huang, D. Xu, M. Yang, Y. Zhu, L. Shen, et al. Discovery and preclinical evaluations of JBD0131, a novel nitrodihydro-imidazooxazole anti-tuberculosis agent. Bioorg Med Chem Lett, 72 (2022), p. 128871
[95]
J.J. Yu, S.J. Tang. Annual progress of chemotherapy of multidrug/rifampicin-resistant tuberculosis in 2022. Chin J Tuberc Respir Dis, 46 (1) (2023), pp. 62-66
[96]
S. Guo, B. Wang, L. Fu, X. Chen, W. Zhang, H. Huang, et al. In vitro and in vivo activity of oxazolidinone candidate OTB-658 against Mycobacterium tuberculosis. Antimicrob Agents Chemother, 65 (11) (2021), p. e0097421
[97]
J. Jiang, Y. Liu, X. Liu, D. Zhang, H. Huang, B. Wang, et al. Simultaneous determination of a novel oxazolidinone anti-tuberculosis OTB-658 and its metabolites in monkey blood by LC-MS/MS. J Chromatogr B Analyt Technol Biomed Life Sci, 1167 (2021), p. 122552
[98]
H. Liu, H. Zhu, L. Fu, W. Zhang, X. Chen, B. Wang, et al. Efficacy of replacing linezolid with OTB-658 in anti-tuberculosis regimens in murine models. Antimicrob Agents Chemother, 67 (2) (2023), p. e0139922
[99]
Q. Gao, X. Huang, Z. Jiang, G. Liu, Y. Xiao, L. Sun, et al. A rapid and sensitive LC-ESI-MS/MS method for the detection of YF-49-92.MLS in rat plasma. Bioanalysis, 5 (20) (2013), pp. 2521-2530
[100]
M. Karvouniaris, M.P. Almyroudi, M.H. Abdul-Aziz, S. Blot, E. Paramythiotou, E. Tsigou, et al. Novel antimicrobial agents for Gram-negative pathogens. Antibiotics, 12 (4) (2023), p. 12
[101]
C.Y. Zhao, Y. Lv, Y. Zhu, M.J. Wei, M.Y. Liu, X.W. Ji, et al. A first-in-human safety, tolerability, and pharmacokinetics study of benapenem in healthy Chinese volunteers. Antimicrob Agents Chemother, 63 (3) (2019), p. 63
[102]
H. Yang, M. Zhang, Y. Chen, H. Ren, H. Zhang, C. Yu, et al. Pharmacokinetics of benapenem for injection in subjects with mild to moderate renal impairment. Eur J Clin Pharmacol, 78 (7) (2022), pp. 1079-1086
[103]
Sihuan Pharmaceutical Holdings Group Ltd. A study to assess efficacy and safety intravenous benapenem in patients with complicated urinary tract infection (cUTI) or acute pyelonephritis (AP) [Internet]. Bethesda: National Library of Medicine; [cited 2023 Jun 27]. Available from: https://clinicaltrials.gov/study/NCT04505683?tab=history&a=1.
[104]
Sihuan Pharmaceutical. Xuanzhu Biopharm entered into an exclusive licensing agreement with new Asia pharmaceutical for the development and commercialization of benapenem and plazomincin in the greater China territory [Internet]. Beijing: Sihuan Pharmaceutical; 2022 [cited 2023 Jun 27]. Available from: https://ir.sihuanpharm.com/en/investor-relations/latest-news/investor-news/xuanzhu-biopharm-entered-into-an-exclusive-licensing-agreement-with-new-asia-pharmaceutical-for-the-development-and-commercialization-of-benapenem-and-plazomincin-in-the-greater-china-territory/.
[105]
G. Li, Y. Liu, H. Hu, S. Yuan, L. Zhou, X. Chen. Evolution of innovative drug R&D in China. Nat Rev Drug Discov, 21 (8) (2022), pp. 553-554
[106]
Ian Lloyd. The Pharma R&D Annual Review 2022: 30th Anniversary Infographic & Whitepaper [Internet]. London: Pharma Intelligence UK Limited; 2022 [cited 2023 Jun 27]. Available from: https://pages.pharmaintelligence.informa.com/rdreview.
[107]
National Health Commission of the People’s Republic of China. Status report on antimicrobial administration and antimicrobial resistance in China. Beijing: Beijing Peking Union Medical College Press; 2022.
[108]
C. Årdal, M. Balasegaram, R. Laxminarayan, D. McAdams, K. Outterson, J.H. Rex, et al. Antibiotic development—economic, regulatory and societal challenges. Nat Rev Microbiol, 18 (5) (2020), pp. 267-274
[109]
A. Mullard. Achaogen bankruptcy highlights antibacterial development woes. Nat Rev Drug Discov, 18 (6) (2019), p. 411
[110]
E. Mahase. UK launches subscription style model for antibiotics to encourage new development. BMJ, 369 (2020), p. m2468
[111]
A. Mullard. UK outlines its antibiotic pull incentive plan. Nat Rev Drug Discov, 19 (5) (2020), p. 298
[112]
M.C. De Souza, A.M. de Souza Antunes. Pipeline of known chemical classes of antibiotics. Antibiotics, 2 (4) (2013), pp. 500-534
[113]
S. Walesch, J. Birkelbach, G. Jézéquel, F.P.J. Haeckl, J.D. Hegemann, T. Hesterkamp, et al. Fighting antibiotic resistance-strategies and (pre)clinical developments to find new antibacterials. EMBO Rep, 24 (1) (2023), p. e56033
[114]
E.K. McCreary, E.L. Heil, P.D. Tamma. New perspectives on antimicrobial agents: cefiderocol. Antimicrob Agents Chemother, 65 (8) (2021), p. e0217120
[115]
J. Qi, Q. Wang, Z. Yu, X. Chen, F. Wang. Innovative drug R&D in China. Nat Rev Drug Discov, 10 (5) (2011), pp. 333-334
[116]
S. Karakonstantis, M. Rousaki, E.I. Kritsotakis. Cefiderocol: systematic review of mechanisms of resistance, heteroresistance and in vivo emergence of resistance. Antibiotics, 11 (6) (2022), p. 11
[117]
N.K. Prasad, I.B. Seiple, R.T. Cirz, O.S. Rosenberg. Leaks in the pipeline: a failure analysis of Gram-negative antibiotic development from 2010 to 2020. Antimicrob Agents Chemother, 66 (5) (2022), p. e0005422
[118]
T.K. Burki. Development of new antibacterial agents: a sense of urgency needed. Lancet Respir Med, 9 (6) (2021), p. e54
[119]
X. Su, H. Wang, N. Zhao, T. Wang, Y. Cui. Trends in innovative drug development in China. Nat Rev Drug Discov, 21 (10) (2022), pp. 709-710
[120]
T.A. Black, U.K. Buchwald. The pipeline of new molecules and regimens against drug-resistant tuberculosis. J Clin Tuberc Other Mycobact Dis, 25 (2021), p. 100285
PDF(1650 KB)

Accesses

Citation

Detail
段落导航
相关文章

/

〈 〉