The original candidate new drug ACT001, developed by Professor Chen Yue of the School of Chemistry of Nankai University for 11 years, is undergoing clinical trials in China, Australia and the United States, with indications including malignant glioma, a world medical problem. Recently, a number of Chinese and foreign doctors who presided over the trial announced some of the clinical trial results of ACT001 at the academic conferences of the American Society of Clinical Oncology (ASCO) and the Society of Neuro-Oncology (SNO): the candidate new drug was initially proved to be safe and effective, and one of the patients with relapsed glioblastoma (GBM) was treated with a single drug for more than 50 months and maintained a complete remission state for more than 27 months.
Left: MRI image before enrolling patients with relapsed GBM (March 2017). Right: The patient's MRI after ACT001 monotherapy achieved complete remission.
Rated IV by the World Health Organization (WHO), GBM is a highly malignant intracranial glioma with a high recurrence rate, a median survival of less than 2 years, and a long-term survival rate of about 4%. Currently, the only standard drug for the treatment of GBM is temozolomide, but it can only prolong the median survival of patients by 2.5 months. In adult recurrent GBM, Professor Lickliter reported the excellent safety of the immunomodulatory agent ACT001, as well as long-term survival cases: in March 2017, a patient with recurrent GBM in Australia joined the Australian clinical trial, enrolled in the intracranial tumor body size of nearly 4 cm, after ACT001 single-drug long-term treatment, reached complete remission in October 2018. As of now, the patient has been taking the drug for more than 50 months and is still in complete remission. Professor Lickliter introduced that the clinical trial of ACT001 combined with PD-1 immunotherapy for recurrent GBM is also underway.
ACT001 is a new structural small molecule compound created by Professor Chen Yue's research group, which is prepared from feverfew lactone, which was first extracted from the traditional herbal feverfew in Western countries. Feverfew lactone has a selective killing effect on tumor stem cells, but it is extremely low in feverfew. Chen Yue's research group conducted a lot of exploration, and finally found that the content of feverfeld in the root bark of Xinyi (mountain magnolia), a unique plant in China, was as high as 9.6%, and the actual extraction rate was stable at 5%-6%. Through semi-synthetic means, the team made chemical structural improvements to the feverfew lactone to obtain DMAMCL (i.e., ACT001). This small molecule compound can enter the bloodstream orally, and can break through the blood-brain barrier and act directly on brain tumor foci.
ACT001 has completely independent intellectual property rights, has been granted more than 20 countries of patent authorization, in 2017 by the U.S. Food and Drug Administration and the European Union Food and Drug Administration "orphan drug" qualification certification, has been in Australia, China, the United States to carry out clinical trials, of which 6 are clinical Phase 2 or 1b/2a, 2 for pediatric tumor Phase 1 clinical, indications include: glioblastoma, children's diffuse endogenous pontine glioma, cancer brain metastases, optic nerve myelitis and lung fibrosis.
Figure A: MRI image before enrollment, showing a large number of diffuse lesions in a red circle. Figure B: Image of ACT001 after monotherapy, tumor cell density decreased significantly.
Chen Yue introduced that the potential use of ACT001 is not limited to the treatment of glioma, the team also found that ACT001 can improve the survival rate of animals after radiation, and has applied for a patent for its use of radiotherapy protection. In addition, scientific peers have also discovered the use of ACT001 in the treatment of a variety of inflammations, cancers and fibrosis.
"Among the 8 clinical trials currently carried out, the clinical trial of Phase 2 of Pulmonary Fibrosis Clinic in Australia and China for the treatment of cancer brain metastases is nearly completed, and the cooperative company Suntech Pharmaceutical Edge Group is vigorously promoting registered clinical trials and Phase 3 clinical trials." Chen Yue said.
It is worth noting that the dosage of drugs in ACT001 clinical trials has risen sharply, and the demand for feverfew lactone and Xinyi (mountain magnolia) root bark has also increased significantly. Cooperative enterprises have set up Xinyi tree planting demonstration bases in many places to promote the development of Xinyi tree planting industry, and to a certain extent, while supporting scientific research, they have also achieved good social benefits of helping farmers increase income.
The transformation of the results of ACT001 has been supported by the national "Twelfth Five-Year Plan" and "Thirteenth Five-Year Plan" major special projects for new drug creation and Tianjin major anti-cancer projects. ACT001's global clinical trials and achievement transformations, in addition to the full promotion of the cooperative enterprise Suntech Pharmaceutical Group, have also received strong support from Tianjin Municipal Science and Technology Bureau, Tianjin Foreign Specialized Bureau, Tianjin Science and Technology Association and other departments, as well as local governments in Henan, Jiangsu, Inner Mongolia, Anhui, Guangdong and other local governments.
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Yue Chen, Ph.D., Professor, Institute of Elemental Organic Chemistry, Research Areas: Anti-Cancer Stem Cell Medicinal Chemistry; Complex Anti-Cancer Natural Products Target Exploration.
Honors and Awards: The Third Batch of Outstanding People of Tianjin in 2020; The Winner of the National Outstanding Youth Science Fund in 2016; The Introduction of Talents at The High Level Overseas in 2013; The "100 Young Academic Leaders" of Nankai University; the First Level of the "131" Innovative Talent Training Project in Tianjin; the New Century Excellent Talents Support Program of the Ministry of Education; the Winner of the Applied Research Project of the Fok Ying Tung Education Foundation For Young Teachers Fund of Colleges and Universities; and the Leader of the Innovation Team in key areas of the Tianjin Innovative Talent Promotion Program.
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The material of this article comes from: Nankai University News Network, the official website of the School of Chemistry of Nankai University, etc