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    Home > Active Ingredient News > Antitumor Therapy > The effectiveness of killing cancer cells is 40 times higher!

    The effectiveness of killing cancer cells is 40 times higher!

    • Last Update: 2021-10-21
    • Source: Internet
    • Author: User
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    In nature, there are many types of fungi that can infect and kill insects.
    They play an important role in regulating insect populations and maintaining ecological balance.
    Cordyceps is neither insect nor grass, but is formed by fungi that kill insects.
    Worm complex
    .

    The representative species of Cordyceps, such as Cordyceps sinensis and Cordyceps militaris (also known as Cordyceps militaris), have a long history of edible and medicinal use, and many have been recorded in ancient books
    .

    In 1951, German scientists discovered that the core component of Cordyceps, 3'-deoxyadenosine (3'-dA), has multiple pharmacological activities such as antibacterial, anti-inflammatory, anti-viral, anti-tumor and immune regulation
    .

    In the following decades, scholars from various countries have conducted extensive research on cordycepin and have confirmed that it has anti-cancer activity in vitro
    .

    In 2017, a study published in Cell Chemical Biology by Wang Chengshu's research group from the Shanghai Institute of Plant Physiology and Ecology of the Chinese Academy of Sciences provided molecular evidence for the anti-cancer activity of Cordyceps militaris
    .

    However, since cordycepin (3'-dA) enters the body, it is rapidly hydrolyzed by the circulating enzyme adenosine deaminase (ADA), which is widely present in various tissues, and its half-life is limited to less than 1.
    6 minutes in plasma.
    Extremely low
    .

    Therefore, 3'dA is not used as an anti-cancer therapy
    .

    In order to improve the anti-cancer and clinical evaluation of cordycepin as a cancer drug, the University of Oxford and the biopharmaceutical company NuCana used their new ProTide technology to extract a new chemotherapeutic drug NUC- from cordycepin (3'-dA).
    7738
    .

    Recently, in this study published in "Clinical Cancer Research", the effectiveness of the research team NUC-7738 led by the University of Oxford in in vitro and phase 1 clinical trials
    .

    They found that NUC-7738 is 40 times more effective in killing cancer cells than its parent compound, and is well tolerated by patients, and shows encouraging signs of anticancer activity in patients with advanced solid tumors
    .

    Generally, when cordycepin enters the body, it must enter the cancer cell through the nucleoside transporter (hENT1), and must be converted into the active anti-cancer metabolite, namely 3'-dATP, by phosphorylase (ADK), and then quickly in the blood Decomposed by ADA enzyme
    .

    Therefore, these drug resistance mechanisms related to transport, activation, and decomposition result in the failure of anti-cancer metabolites to be transported to the tumor smoothly
    .

    In this study, the researchers described the synthesis of NUC-7738
    .

    This is a new protein that is partially fused with 3'-dA monophosphate (3'-dAMP) and phosphoramide to overcome these biochemical properties
    .

    NuCana has designed this protein with the new ProTide technology, which can bypass these resistance mechanisms and produce high levels of active anti-cancer metabolite 3'-dATP in cancer cells
    .

    ProTide technology is a new method of introducing chemotherapy drugs into cancer cells
    .

    It works by attaching small chemical groups to nucleoside analogues (such as cordycepin).
    Once it reaches the patient's cancer cells, it will be metabolized and the activated drug will be released
    .

    This technology has been successfully applied to the FDA-approved antiviral drugs Remdesivir and Sofusbuvir for the treatment of different types of viral infections, such as hepatitis C, Ebola and the new coronavirus
    .

    NUC-7738 is 7-40 times more potent than 3'-dA in a series of cancer cell lines, and induces cell death through apoptosis
    .

    Research results show that by overcoming key cancer drug resistance mechanisms, NUC-7738 has a greater cytotoxic activity than cordycepin against a series of cancer cells
    .

    Encouraging pharmacokinetic data in the ongoing Phase I trial shows that NUC-7738 is resistant to degradation by adenosine deaminase (ADA) and can release active 3-dAMP into cells where it is rapidly transformed 3'-dATP, a key anti-cancer metabolite, is detected 2 hours after the start of the infusion, and its half-life is about 50 hours
    .

    Moreover, NUC-7738 is well tolerated and shows encouraging signs of anticancer activity in patients with advanced solid tumors
    .

    These findings provide a proof of concept that NUC-7738 overcomes the anti-cancer mechanism that limits 3'-DA activity and supports further clinical evaluation
    .

    Link to the paper: https://clincancerres.
    aacrjournals.
    org/content/early/2021/09/08/1078-0432.
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