选择性Toll样受体7激动剂——维沙莫德
|
摘要
中国是世界上乙肝患者最多的国家,现有抗乙肝病毒(HBV)的药物只能抑制病毒,不能实现完全治愈。维沙莫德(GS-9620)是由美国吉利德公司开发的一种选择性Toll样受体7 (TLR7)激动剂,其可通过激活TLR7识别入侵的病毒,触发先天免疫反应抑制病毒复制,同时触发适应性免疫反应杀死被感染的细胞。虽然其Ⅱ期临床研究未达到预期,但GS-9620与现有抗病毒药物相结合,可能给现有治疗方案带来全新的变革。同时,GS-9620在抗HIV-1的临床前实验中表现良好,2项HIV-1相关的临床试验现已被开展。笔者就GS-9620的基本信息、作用机制和临床试验情况作一概述。
China is the country with the largest number of hepatitis B patients in the world. The existing anti-hepatitis B virus(HBV) drugs can only inhibit the reproduction of the virus rather than achieve a complete cure. GS-9620 is a selective TLR7 agonist developed by Gilead Company of the United States, which can activate TLR7 to identify invading viruses, trigger innate immune response to inhibit virus replication, and trigger adaptive immune response to kill infected cells. Although the Phase II clinical studies for GS-9620 did not meet expectations, it combined with existing antiviral drugs may bring new changes to existing treatment programs. At the same time, GS-9620 performed well in preclinical trials of anti-HIV-1, including two HIV-1 related clinical trials have been carried out The basic information, mechanism and clinical trials of GS-9620 were summarized
China is the country with the largest number of hepatitis B patients in the world. The existing anti-hepatitis B virus(HBV) drugs can only inhibit the reproduction of the virus rather than achieve a complete cure. GS-9620 is a selective TLR7 agonist developed by Gilead Company of the United States, which can activate TLR7 to identify invading viruses, trigger innate immune response to inhibit virus replication, and trigger adaptive immune response to kill infected cells. Although the Phase II clinical studies for GS-9620 did not meet expectations, it combined with existing antiviral drugs may bring new changes to existing treatment programs. At the same time, GS-9620 performed well in preclinical trials of anti-HIV-1, including two HIV-1 related clinical trials have been carried out The basic information, mechanism and clinical trials of GS-9620 were summarized
引文
[1]Geng C A, Chen J J. The progress of anti-HBV constituents from medicinal plants in China[J]. Nat Prod Bioprospect, 2018, 8(4):227-244.
[2]Marcellin P, Dusheiko G, Zoulim F,et al.EASL Clinical Practice Guidelines:Management of Chronic Hepatitis B[J].J Hepatol,2009,50(2):227-242.
[3]van Campenhout M J, Janssen H L. How to achieve immune control in chronic hepatitis B[J]. Hepatol Int, 2015, 9(1):9-16.
[4]Lamb C, Arbuthnot P. Activating the innate immune response to counter chronic hepatitis B virus infection[J]. Expert Opin Biol Ther, 2016, 16(12):1517-1527.
[5]Clinical Trials.gov.GS-9620[EB/OL].(2016-12-19)[2018-06-11]. https://www.clinicaltrials.gov/.
[6]Gane E J, Lim Y S, Gordon S C, et al. The oral toll-like receptor-7 agonist GS-9620 in patients with chronic hepatitis B virus infection[J]. J Hepatol, 2015, 63(2):320-328.
[7]Lawitz E, Gruener D, Marbury T, et al. Safety, pharmacokinetics and pharmacodynamics of the oral toll-like receptor 7 agonist GS-9620 in treatment-naive patients with chronic hepatitis C[J].Antivir Ther, 2015, 20(7):699-708.
[8]Janssen H L A, Brunetto M R, Kim Y J, et al. Safety, efficacy and pharmacodynamics of vesatolimod(GS-9620)in virally suppressed patients with chronic hepatitis B[J]. J Hepatol, 2018, 68(3):431-440.
[9]Agarwal K, Ahn S H, Magdy E, et al. Safety and efficacy of vesatolimod(GS-9620)in patients with chronic hepatitis B who are not currently on antiviral treatment[J]. J Viral Hepat, 2018, 25(5):439-615.
[10]Ethan G, Adarsh J, Natarajan A, et al. Pharmacodynamic response to oral administration of the selective toll-like receptor 8 agonist GS-9688 in healthy volunteers[R].Japan:AASLD2018, 2018.
[11]Borducchi E N, Liu J, Nkolola JP, et al. Antibody and TLR7 agonist delay viral rebound in SHIV-infected monkeys[J]. Nature,2018, 563(7731):360-364.
[2]Marcellin P, Dusheiko G, Zoulim F,et al.EASL Clinical Practice Guidelines:Management of Chronic Hepatitis B[J].J Hepatol,2009,50(2):227-242.
[3]van Campenhout M J, Janssen H L. How to achieve immune control in chronic hepatitis B[J]. Hepatol Int, 2015, 9(1):9-16.
[4]Lamb C, Arbuthnot P. Activating the innate immune response to counter chronic hepatitis B virus infection[J]. Expert Opin Biol Ther, 2016, 16(12):1517-1527.
[5]Clinical Trials.gov.GS-9620[EB/OL].(2016-12-19)[2018-06-11]. https://www.clinicaltrials.gov/.
[6]Gane E J, Lim Y S, Gordon S C, et al. The oral toll-like receptor-7 agonist GS-9620 in patients with chronic hepatitis B virus infection[J]. J Hepatol, 2015, 63(2):320-328.
[7]Lawitz E, Gruener D, Marbury T, et al. Safety, pharmacokinetics and pharmacodynamics of the oral toll-like receptor 7 agonist GS-9620 in treatment-naive patients with chronic hepatitis C[J].Antivir Ther, 2015, 20(7):699-708.
[8]Janssen H L A, Brunetto M R, Kim Y J, et al. Safety, efficacy and pharmacodynamics of vesatolimod(GS-9620)in virally suppressed patients with chronic hepatitis B[J]. J Hepatol, 2018, 68(3):431-440.
[9]Agarwal K, Ahn S H, Magdy E, et al. Safety and efficacy of vesatolimod(GS-9620)in patients with chronic hepatitis B who are not currently on antiviral treatment[J]. J Viral Hepat, 2018, 25(5):439-615.
[10]Ethan G, Adarsh J, Natarajan A, et al. Pharmacodynamic response to oral administration of the selective toll-like receptor 8 agonist GS-9688 in healthy volunteers[R].Japan:AASLD2018, 2018.
[11]Borducchi E N, Liu J, Nkolola JP, et al. Antibody and TLR7 agonist delay viral rebound in SHIV-infected monkeys[J]. Nature,2018, 563(7731):360-364.