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    Home > Active Ingredient News > Drugs Articles > There is no blockbuster yet. Johnson & Johnson, Roche, and GSK have joined. Which drugs in the field of hepatitis B are worth looking forward to?

    There is no blockbuster yet. Johnson & Johnson, Roche, and GSK have joined. Which drugs in the field of hepatitis B are worth looking forward to?

    • Last Update: 2021-08-04
    • Source: Internet
    • Author: User
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    July 28 is the birthday of the late Nobel Prize winner Baruch Bloomberg.
    To commemorate the discoverer of the hepatitis B virus, the World Health Organization has decided that the annual World Hepatitis Day has been set as 7 since 2011.
    On the 28th
    .
    There are many types of hepatitis, and the biggest threat to human health is hepatitis B and C; the birth of sofosbuvir has now conquered hepatitis C; and hepatitis B still seriously threatens human life and health, especially for our country, the discovery of therapeutic drugs It is more dependent on ourselves


    .


    The global burden of HBV

    Hepatitis B virus (HBV) is a typical hepatotropic DNA virus.
    Chronic infection with hepatitis B virus can develop into liver cirrhosis, decompensation of liver function and even liver cancer
    .
    According to statistics, about 686,000 deaths in 2013 were caused by hepatitis B virus infection, and an estimated 257 million people worldwide suffer from chronic hepatitis B; although the current vaccine is very successful, infection is still a problem that threatens health.


    And medication is not satisfactory



    HBV life cycle

    Through years of research, a more detailed analysis of the complex life cycle of HBV has been carried out, and a number of potential targets have been proposed
    .

    HBV virus is first co-transported into hepatocytes through hepatitis B surface antigen (HBsAg), and then the virus is transported to the nuclear pore by releasing the capsid, and HBV further releases circular DNA (rcDNA) to be delivered to the nucleus
    .
    In the cell nucleus, rcDNA is converted by host polymerase into covalently closed circular DNA, namely cccDNA, which can be present in infected hepatocytes at a low copy number


    .


    cccDNA is the original template for the replication of hepatitis B virus pre-genomic RNA.
    Although its content is small, there are only about 5-50 copies in each liver cell, it has very important significance for the replication of hepatitis B virus and the establishment of infection status.
    Only the cccDNA in the nucleus can completely eliminate the virus carrying status of hepatitis B patients, which is considered to be the main goal of antiviral therapy
    .
    The proteins and enzymes involved in this process are naturally considered to be proven or potential therapeutic targets; such as HBV polymerase/reverse transcriptase (pol/RT), hepatitis B x protein, core protein, hepatitis B e antigen (HBeAg), and the like


    .



    Classic listed drugs

    Although there is no cure for HBV, there are currently many drugs used to control the clinical course, such as classic lamivudine, adefovir dipivoxil, tenofovir, and so on
    .

    ➣ Lamivudine

    It is a nucleoside analogue and is currently the most effective first-line drug for the treatment of chronic HBV.
    Its mechanism of action is to inhibit the activity of viral DNA polymerase and reverse transcriptase, and it has a competitive inhibitory effect on the synthesis and elongation of the viral DNA chain
    .
    However, because the drug cannot eliminate the replication of HBV cccDNA in the cell, it has no effect on the hepatitis B virus cccDNA, and the recurrence rate is high after stopping the drug.


    Long-term application can cause virus mutation


    The main domestic companies applying for the registration of this product include: GlaxoSmithKline, Shanghai Desano, Anhui Baker Bio, Shijiazhuang Longze Pharmaceutical, Wanquan Want Pharmaceutical, Fujian Guangshengtang Pharmaceutical, Beijing Fuyuan Pharmaceutical, Anhui Pioneer pharmaceutical, Shandong Elohim pharmaceutical, Zhongfu medicine, and so on
    .

    ➣ Adefovir dipivoxil

    An analogue of acyclic deoxyadenosine monophosphate that is phosphorylated by kinases into an active diphosphate in the cell.
    This product competes with the enzyme's natural substrate deoxyadenosine triphosphate to inhibit hepatitis B virus DNA polymerase.
    Or through integration into the viral chain to cause chain termination
    .
    Large-scale clinical studies have shown that in the treatment of HBeAg-positive and negative chronic hepatitis B, adefovir dipivoxil develops drug-resistant mutations later and has a low incidence


    .


    The main domestic companies applying for the registration of this product are: Beijing Shuanglu Pharmaceutical, Zhengda Tianqing Pharmaceutical, Fujian Guangshengtang Pharmaceutical, GlaxoSmithKline, Qilu Pharmaceutical, Shanghai Yishengyuan Pharmaceutical, Chenxin Pharmaceutical, Hangzhou China and the US East China pharmaceutical, Nanjing Wellman, and so on
    .

    ➣ Entecavir

    It is a guanine nucleoside analog, which has an inhibitory effect on HBV polymerase; it can be phosphorylated into an active triphosphate, and the intracellular half-life is 15h
    .
    By competing with the natural substrate of HBV polymerase, deoxyguanosine triphosphate, to inhibit the activity of viral polymerase (reverse transcriptase)


    .


    The main domestic companies applying for the registration of this product are: Sino-US Shanghai Squibb Pharmaceuticals, Fujian Guangshengtang Pharmaceuticals, Shandong Lukang Pharmaceuticals, Hainan Zhonghe Pharmaceuticals, Zhengda Tianqing Pharmaceuticals, Jiangxi Qingfeng Pharmaceuticals, Hunan Warner Pharmaceuticals plant, Suzhou East Swiss pharmaceutical, Shandong new era of medicine, Hunan daughter medicine work together, and so on
    .

    Drugs under development worldwide

    In order to overcome hepatitis B, research has never stopped, and most studies believe that the ultimate goal of treating hepatitis B is to eliminate nuclear cccDNA or inhibit the transcriptional activity of cccDNA
    .
    At present, the research direction is mainly focused on controlling virus invasion, inhibiting viral DNA transcription, inhibiting the packaging and release of virus particles, especially blocking and degrading cccDNA, etc.
    ; "Clin Liver Dis" summarizes the current HBV drug Pipeline as follows
    .

    Table 4.
    1 Treatment methods in clinical development of hepatitis B



    (Reference: doi.
    org/10.
    1016/j.
    cld.
    2019.
    04.
    006)

    summary

    Following the milestone breakthrough of HCV therapeutic drugs, in the past few years, researchers' interest in the treatment of HBV has revived.
    It is the first time after more than 20 years to explore multiple new targets other than HBV pol/RT; although there is no blockbuster yet.
    However, it is not difficult to see from the above-mentioned drug development pipeline that with breakthroughs in molecular biology and the introduction of new therapies, HBV will surely be controlled like HCV in the most effective way!

    refer to:

    refer to:

    1.
    Drugs in the Pipeline for HBV.
    doi.
    org/10.
    1016/j.
    cld.
    2019.
    04.
    006

    1.
    Drugs in the Pipeline for HBV.
    doi.
    org/10.
    1016/j.
    cld.
    2019.
    04.
    006

    2.
    Global Epidemiology of Viral Hepatitis.
    doi.
    org/10.
    1016/j.
    gtc.
    2020.
    01.
    001

    2.
    Global Epidemiology of Viral Hepatitis.
    doi.
    org/10.
    1016/j.
    gtc.
    2020.
    01.
    001

    3.
    CDE official website

    3.
    CDE official website
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