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New drug use of azd3965

A 1.AZD3965, pharmacy technology, applied in the field of medicine, can solve the problem of no AZD3965

Active Publication Date: 2022-04-08
SYNOGENBIOPHARMACO LTD NANJING CHINA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

But there is no report about AZD3965 inducing endogenous cardiomyocyte proliferation

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034] Embodiment 1, the in vitro test of AZD3965 promoting the proliferation of rat cardiomyocytes

[0035] (1) Culture of Cardiomyocytes of SD Rats

[0036] Cardiomyocytes from SD rats born 3 days old were isolated and cultured in DMEM high glucose medium (Hyclone) + 5% horse serum (GIBCO) at 37 degrees in a 5% carbon dioxide incubator.

[0037] (2) Experimental grouping and processing

[0038]Isolate cardiomyocytes from SD rats, add 5% horse serum (GIBCO) + DMEM high-glucose medium (Hyclone), and add cytarabine (final concentration 20umol / L) to inhibit the growth of non-cardiomyocytes. Infect cTnT-mAG-hGeminin (1 / 110) virus (MOI value of virus infection=100) after 48 hours of adherence, after another 24 hours, replace with DMEM culture medium containing 0.5% FBS, add drugs in groups, and group as follows:

[0039] a. Experimental group: treated with AZD3965 (the final concentration in the culture medium is 2 μmol / L) for 24 hours.

[0040] b. Blank control group: add the ...

Embodiment 2

[0044] Test results such as figure 1 shown. Depend on figure 1 It can be seen that after AZD3965 treatment, mAG-hGeminin (1 / 110) positive cardiomyocytes increased by 2 times compared with the blank control group (0.5% FBS+DMSO). Mean±SEM; **P<0.01. Example 2. In vitro experiment of AZD3965 promoting cytokinesis of cardiomyocytes in newborn mice with MADM

[0045] (1) Isolation and culture of cardiomyocytes from P3 MADM mice

[0046] Isolation of P3 MADM-ML-11 by Two-Step Digestion TG / GT mouse cardiomyocytes. Take P3MADM-ML-11 TG / GT Mouse left ventricular tissue was digested overnight at 4°C in 0.25% trypsin (including EDTA). The heart tissue was transferred to digestion solution containing 0.5 mg / ml collagenase (Gibco, 216320) and 5 mg / ml BSA (MP, Y180306), and digested at 37°C for about 30 minutes, 6 minutes each time. Collect each cell suspension, centrifuge at 1000g for 5 min, discard the supernatant, resuspend the cells in DMEM high-glucose medium containing 10% FB...

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Abstract

The invention discloses a new medicine application of AZD3965. The new use is the application of AZD3965 or its pharmaceutically acceptable salts and esters in the preparation of drugs for promoting cardiomyocyte proliferation. The present invention proves through experiments that AZD3965 can promote the proliferation of cardiomyocytes in rats and the cytokinesis of cardiomyocytes in newborn mice with MADM. Therefore, AZD3965 can be used in related fields such as preparation of drugs for promoting myocardial cell proliferation and drugs for treating or preventing heart disease, providing a new drug and treatment idea for treating or preventing heart disease such as myocardial infarction.

Description

technical field [0001] The invention belongs to the field of medicine, and in particular relates to a new medicine application of AZD3965. Background technique [0002] At present, cardiovascular disease has become the number one killer threatening human health. There are 40 million heart failure patients worldwide, and it has become the main cause of human death. Studies have found that cardiomyocytes in mammals gradually lose their ability to proliferate after adulthood. Once myocardial infarction occurs, the loss of cardiomyocytes will be irreversible. There are about 2-4 billion cardiomyocytes in an adult, about 25% of cardiomyocytes will be lost within a few hours after myocardial infarction, and the remaining cardiomyocytes have very limited proliferation ability, which is not enough to restore the contractile function of the heart, and the patient will eventually suffer from heart failure die. To solve this problem, in addition to surgery, basic translational resear...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/519A61P9/04A61P9/10A61P9/00C12N5/077
CPCA61K31/519A61P9/04A61P9/10A61P9/00C12N5/0657C12N2501/999
Inventor 卜晔杜建勇郑丽霞吴青朱小君熊敬维
Owner SYNOGENBIOPHARMACO LTD NANJING CHINA
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