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New drug use of bml-28-4

A BML-284, 1. BML-284 technology, applied in the field of medicine, can solve the problem of endogenous cardiomyocyte proliferation without BML-284, and achieve the effect of promoting cardiomyocyte proliferation and promoting proliferation

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

However, there is no relevant report on the induction of endogenous cardiomyocyte proliferation by BML-284

Method used

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  • New drug use of bml-28-4
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  • New drug use of bml-28-4

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0040] Embodiment 1, the in vitro test of BML-284 promoting the proliferation of rat cardiomyocytes

[0041] (1) Culture of Cardiomyocytes of SD Rats

[0042] 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.

[0043] (2) Experimental grouping and processing

[0044] 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:

[0045] a. Experimental group: treated with BML-284 (the final concentration in the medium is 2 μmol / L) for 24 hours.

[0046] b. Blank control group: add the same am...

Embodiment 2

[0051] Example 2. In vitro test of BML-284 promoting the proliferation of human iPSC-derived cardiomyocytes

[0052] Human induced pluripotent stem cell-induced cardiomyocytes (hiPSC-derived cardiomyocytes) were treated with BML-284 for 48 hours, RPMI1640+DMSO was used as the control (control), washed three times with PBS after 48 hours, 4% PFA (paraformaldehyde) at room temperature Fix for 15 min, wash with PBS three times, block with 1% BSA / PBS / 0.1% Triton for 1 h at room temperature, add primary antibody after 1 h: Anti-Cardiac Troponin T (1:300, abcam, mouse, ab8295), Phospho-Histone H3 (Ser10) Antibody (1:300, CST, rabbit, 9701S), overnight at 4°C, wash 4 times with 1% BSA / PBS / 0.02% Tween, add secondary antibody: goat anti-rabbit IgG (H+L) highly cross-adsorbed secondary Antibody (1:500, Invitrogen, A32731), goat anti-mouse IgG (H+L) highly cross-adsorbed secondary antibody (1:500, Life technologies, A21424), placed at room temperature for 1 h, washed with PBS / 0.02% Tween...

Embodiment 3

[0054] Example 3. In vitro test of BML-284 promoting neonatal rat cardiomyocytes to enter the cell cycle

[0055] Isolate rat cardiomyocytes born 3 days old, add BML-284 (the final concentration in the culture medium is 2 μ mol / l), use DMEM+DMSO as the control (control), wash three times with PBS after 48 h, 4% PFA (polymer Formaldehyde) fixed at room temperature for 15 min, washed three times with PBS, blocked at room temperature with 1% BSA / PBS / 0.1% Triton for 1 h, and added primary antibody after 1 h: Anti-α-Actinin (1:300, sigma, mouse, A7811), Phospho-Histone H3 (Ser10) antibody (1:300, CST, rabbit, 9701S), Anti-Ki67 (1:300, abcam, rabbit, ab15580) overnight at 4°C, wash 4 times with 1% BSA / PBS / 0.02% Tween, add two Anti: goat anti-rabbit IgG (H+L) highly cross-adsorbed secondary antibody (1:500, Invitrogen, A32731), goat anti-mouse IgG (H+L) highly cross-adsorbed secondary antibody (1:500, Life technologies, A21424), placed at room temperature for 1 hour, washed 3 times ...

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Abstract

The invention discloses a medicine application of BML-284. The use is the application of BML-284 or a pharmaceutically acceptable salt thereof in the preparation of drugs for promoting cardiomyocyte proliferation. The present invention proves through experiments that BML-284 can promote the proliferation of rat cardiomyocytes. Therefore, BML‑284 can be used in related fields such as the 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 drug application of BML-28-4. 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 research ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/506A61P9/00A61P9/10A61P9/04C12N5/077
CPCA61K31/506A61P9/00A61P9/10A61P9/04C12N5/0657C12N2501/415
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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