Extracellular regulatory protein kinase probe as well as preparation method and application thereof

A technology of protein kinase inhibitors and protein kinases, applied in the field of probes, can solve the problems of no probes for extracellular regulatory protein kinases and the inability to combine inhibitors of the MAPK pathway, so as to improve drug sensitivity, effect, and production yield high effect

Active Publication Date: 2021-12-03
SHENZHEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] The purpose of this application is to provide a probe for extracellular regulated protein kinase and its preparation method and application, aiming to solve the problem that there is no corresponding probe for extracellular regulated protein kinase in the prior art, resulting in that inhibitors of MAPK pathway cannot be better compared with Problems with ERK1 / 2 binding

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  • Extracellular regulatory protein kinase probe as well as preparation method and application thereof
  • Extracellular regulatory protein kinase probe as well as preparation method and application thereof
  • Extracellular regulatory protein kinase probe as well as preparation method and application thereof

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preparation example Construction

[0047] The second aspect of the embodiment of the present application provides a method for preparing an extracellular regulatory protein kinase probe, comprising the following steps:

[0048] S01. Obtaining the calyx calyx medicinal material powder, using an alcohol solution to carry out reflux extraction treatment on the calyx calyx calyx medicinal material powder, and then sequentially concentrating and separating to obtain calyxin;

[0049] S02. After heat-mixing the elisonin and the oxidizing agent, a quenching reaction is performed to obtain the first mixture;

[0050] S03. The first mixture is purified with an organic solvent, and concentrated and separated to obtain the extracellular regulatory protein kinase probe.

[0051] The preparation method of extracellular regulatory protein kinase probe provided in the second aspect of the present application, the preparation method is prepared from eelicalline extracted from natural plant species as a raw material, and the ex...

Embodiment 1

[0074] Preparation of extracellular regulatory protein kinase probe Laxiflorin A of structural formula I-1

[0075] The extracellular regulatory protein kinase probe Laxiflorin A of structural formula I-1 is as follows :

[0076]

[0077] The preparation method is as follows, and the detailed process is as follows:

[0078] (1) Purchasing freshly-picked medicinal materials of Chaecilia chinensis, and after natural air-drying, separate the dried medicinal materials of Chalyx chinensis mixed with branches and leaves, extract by reflux of 80% methanol water for 2 hours, prepare samples, and then go through chromatographic separation, gel column decolorization, recrystallization and preparative liquid phase separation etc. methods to obtain calyxin (EB).

[0079] (2) DMP Dess-Martin reagent (85 mg, 0.2 mmol) was added to a solution of Eriocalyxin B (34 mg, 0.1 mmol) in DCM (10 mL) at room temperature. Slowly raise the temperature to 40° C., stir for 30 min and then cool t...

Embodiment 2

[0084] Preparation of extracellular regulatory protein kinase probe Laxiflorin A-A9-TH of structural formula I-2

[0085] The extracellular regulatory protein kinase probe Laxiflorin A-A9-TH of structural formula I-2 is as follows :

[0086]

[0087] The preparation method is as follows, and the detailed process is as follows:

[0088] Take Laxiflorin A (17mg, 0.05mmol) and dissolve it in 1mL of dichloromethane, add the corresponding reactants (0.05mmol), EDCI (0.05mmol) and DMAP (cat.) in turn, continue to react at room temperature for 12 hours, and detect the reaction materials by TLC After disappearing completely, the reaction was quenched by adding saturated aqueous sodium bicarbonate solution, extracted with ethyl acetate (10 mL×3), and the organic phases were combined and concentrated. The product was separated by column chromatography.

[0089] The specific process is as follows:

[0090]

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Abstract

The invention provides an extracellular regulatory protein kinase probe as shown in a formula I. A ring A on the structure can be covalently bound with 178 cysteine of an inactive site on the outer side of an ERK1/2 kinase structure in a specific targeting manner, and can effectively target ERK1/2; and the extracellular regulatory protein kinase probe does not inhibit the binding capacity of ERK1/2 and ATP and the kinase activity, but has targeting property on ERK1/2, so a small-molecule guiding group is provided for protein modification and marking research of targeted ERK kinase, the drug sensitivity of an inhibitor on extracellular regulatory protein kinase is improved, the probe is provided for an extracellular regulatory protein kinase inhibitor, and the extracellular regulatory protein kinase inhibitor is guided to act on the extracellular regulatory protein kinase site in a targeted manner so as to enable the inhibitor to play a role and to improve effect.

Description

technical field [0001] The application belongs to the technical field of probes, and in particular relates to an extracellular regulatory protein kinase probe and its preparation method and application. Background technique [0002] Cells have extremely complex life activities, and these life activities must be strictly regulated. As an open system, it not only needs to communicate with the external environment, but also transmits information between cells. Therefore, in the process of long-term evolutionary development and natural selection, a complex signal transduction network is gradually established, which is formed by the interconnection and interaction of different signal transduction pathways. "cross-talking". In the signaling network, the mitogen-activated protein kinase (MAPK) signaling pathway plays an extremely important role, controlling various physiological processes of cells, such as cell growth, development, division, and death. Extracellular signal-regula...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D405/14A61P35/00A61K31/454
CPCC07D405/14A61P35/00
Inventor 郑多朱礼志江承尧黄均荣
Owner SHENZHEN UNIV
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