Application of compound hu-17 alone or in combination with tyrosine kinase inhibitors in the preparation of drugs for the treatment of chronic myelogenous leukemia

Abstract

The invention discloses application of a compound Hu-17 single or combined tyrosine kinase inhibitor to preparation of medicine for treating chronic myelogenous leukemia. The invention discloses a new treatment scheme of new medicine for treating chronic myelogenous leukemia and the combined tyrosine kinase inhibitor (imatinib and the like) for treating chronic myelogenous leukemia. A new choice is provided for patients resistant to imatinib. Different from a drug action mechanism of a former tyrosine kinase inhibitor, the compound Hu-17 single or combined tyrosine kinase inhibitor and first-line treatment medicine imatinib are used together to inhibit transcription and translation of a pathogenic fusion gene BCR-ABL, so that the disease is possibly healed fundamentally.

Description

technical field [0001] The invention belongs to the field of medicine and biology, and more specifically, the invention relates to the application of compound Hu-17 alone or in combination with tyrosine kinase inhibitor drugs in the preparation of drugs for treating chronic myeloid leukemia. Background technique [0002] Chronic myeloid leukemia (CML) is a blood disease caused by abnormal proliferation of myeloid cells, with an annual incidence of 1.0-1.5 / 100,000 people. The incidence of children is extremely low, and the median age of onset is 50-60. between the ages. Clinical manifestations at onset are lethargy, sweating, anemia, weight loss, abnormal bleeding, and enlarged spleen (Perrotti, D., Jamieson, C., Goldman, J. & Skorski, T.J Clin Invest 120, 2254-2264). The abnormal chromosome formed by the translocation t(9;22)(q34;q11) of chromosomes 9 and 22 is the first Philadelphia chromosome to be discovered, and it is also the main cause of chronic myelogenous leukemia....

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Problems solved by technology

[0003] Although it is effective in treating patients with chronic myelogenous leukemia in the chronic phase, the drug is not effective in treating patients in the accelerated phase and blast phase, and the sustained release rate is less than 40%.

[0005] Tyrosine Kinase Inhibitors (Imatinib / Sti571, Nilotinib, Dasatinib) Have Insignificant Effects on Leukemic Stem Cells in Chronic Myeloid Leukemia Repeated treatment with inhibitors is not effective; treatment with first-generation and second-generation kinase inhibitors can have a better disease progression-free period, but the treatment effect for patients with blastic change has not yet achieved satisfactory curative effect

The mechanism of action of currently available tyrosine kinase inhibitors is to target the BCR-ABL fusion protein and inhibit the activation of the tyrosine kinase, so as to achieve specific targeting and inhibition of the pathogenic protein BCR-ABL, but it does not affect the overall The content of BCR-ABL, the inhibition of BCR-ABL tyrosine kinase activity in leukemia stem cells cannot induce the apoptosis of leukemia stem cells, so the defect of this type of inhibitor is that it cannot completely remove abnormal white blood cells in peripheral blood and bone marrow

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