Application of sinomenine derivatives in the preparation of drugs for treating multiple myeloma

A technology of multiple myeloma and derivatives, applied in the field of medicine, to achieve good medicinal prospects and strong pharmacological effects

Active Publication Date: 2019-05-21
SHANGHAI JIAOTONG UNIV SCHOOL OF MEDICINE +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, there have been reports that sinomenine derivatives can effectively inhibit the inflammatory response involved in IL-6 and IL-1β and inhibit the NF-κB signaling pathway, but there is no research on sinomenine derivatives in MM

Method used

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  • Application of sinomenine derivatives in the preparation of drugs for treating multiple myeloma
  • Application of sinomenine derivatives in the preparation of drugs for treating multiple myeloma
  • Application of sinomenine derivatives in the preparation of drugs for treating multiple myeloma

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0050] Example 1. Table 1 YL064 and its series of sinomenine derivatives inhibit the proliferation of myeloma cell line U266

[0051] Multiple myeloma cells U266 were treated with different concentrations of sinomenine derivatives respectively, and the half inhibition rate (IC) of each compound on U266 cells was detected by CCK8 method after 48 h. 50 ). The results showed that sinomenine derivatives could inhibit the proliferation of U266 cells to varying degrees (Table 1.).

Embodiment 2

[0052] Example 2. YL064 induces apoptosis of human multiple myeloma cell lines and primary myeloma cells

[0053] The multiple myeloma cells U266 and MM1.S cells were treated with different concentrations for 24 hours, and the apoptosis rate was detected by flow cytometry, and the related apoptosis proteins PARP1-1, Caspase3, and Cleaved caspase3 were detected by Westblot. Apoptosis of cell lines was dose- and time-dependent. ( figure 1 C, D, E). Further, we treated the primary cells of 4 cases of myeloma patients with YL064 20μM, and the results showed that YL064 could significantly induce the apoptosis of primary cells, while 40μM YL064 had no effect on normal human peripheral blood mononuclear cells ( figure 1 B).

Embodiment 3

[0054] Example 3. YL064 inhibits activation of STAT3 and inhibits downstream target genes

[0055] In order to study the mechanism of YL06-induced apoptosis in myeloma cells, the effect of YL064 on the STAT3 pathway was observed since the activation of STAT3 signaling pathway mediated by IL-6 is a classical and important pathway involved in the proliferation and invasion of multiple myeloma. U266 cells were treated with different concentrations (2.5, 5, 10, 20 μM) of YL064 for 24 h, and U266 cells were treated with 20 μM of YL064 for different time (6, 12, 24, 48 h), respectively. Among them, p-STAT3 (Tyr705), The expression changes of p-STAT3 (Ser727) and STAT3 showed that YL064 could significantly inhibit the activation of p-STAT3 (Tyr705) in a dose- and time-dependent manner, but did not affect the activation of p-STAT3 (Ser727) ( figure 2 A. figure 2 C). Since the activation of STAT3 is regulated by upstream JAK1 and JAK2, we next examined the effect of YL064 on the JA...

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Abstract

The invention discloses applications of a sinomenine derivative in preparing drugs used for treating multiple myeloma, applications of sinomenine derivative YL064 in preparing JAK1 inhibiting agents, applications of YL064 in preparing STAT3 inhibiting agents, and applications of YL064 in preparing JAK1 and STAT3 dual inhibiting agents. The sinomenine derivative YL064 is safe, is low in toxicity, and is high in pharmacological action, and pharmaceutical prospect is promising.

Description

technical field [0001] The invention relates to the field of medicine, more particularly, to the application of YL064 and its series of sinomenine derivatives in the preparation of medicines for treating multiple myeloma. Background technique [0002] Multiple myeloma (MM) is a malignant clonal proliferative disease of plasma cells, accounting for about 10% of hematological malignancies. The median age of onset of MM is 60-65 years old. The incidence of MM in my country is increasing year by year, and the annual incidence is close to 1 / 100,000. MM is becoming one of the malignant tumors affecting the physical and mental health of the elderly in my country. [0003] The clinical treatment of MM has always been based on cytotoxic chemotherapy drugs such as melphalan, but the long-term effect of chemotherapy is not ideal, and the five-year survival rate is less than 30%. In recent years, with the in-depth study of the pathogenesis of MM, targeted therapy for MM cells and their ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/485A61P35/00A61P19/00
CPCA61K31/485
Inventor 吴英理姚祝军王莹莹吴霖霖朱琦雷虎徐含章
Owner SHANGHAI JIAOTONG UNIV SCHOOL OF MEDICINE
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