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Application of nicotinamide mononucleotide ribose phosphate transferase inhibitor

A single nucleotide, phosphoribosyl sugar technology is applied in the field of nicotinamide mononucleotide phosphoribosyltransferase inhibitor, and achieves the effect of less side effects, good curative effect, prevention or treatment of platelet hyperfunction

Active Publication Date: 2011-04-06
SECOND MILITARY MEDICAL UNIV OF THE PEOPLES LIBERATION ARMY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

In the field of treating hypercoagulable diseases, there is no relevant literature

Method used

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  • Application of nicotinamide mononucleotide ribose phosphate transferase inhibitor
  • Application of nicotinamide mononucleotide ribose phosphate transferase inhibitor
  • Application of nicotinamide mononucleotide ribose phosphate transferase inhibitor

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0022] Example 1 Expression of nicotinamide mononucleotide phosphoribosyltransferase on platelets

[0023] In order to prove that nicotinamide mononucleotide phosphoribosyltransferase can regulate platelet function, it must first be proved that this enzyme exists on platelets. Using the protein dot hybridization technique, it was verified whether nicotinamide mononucleotide phosphoribosyltransferase was expressed on platelets.

[0024] The specific operation process is as follows: Centrifuge the mixed anticoagulant blood (containing sodium citrate) at 25°C-32°C, the speed is 500-800rpm, and the time is controlled within 10 minutes in principle, and take it out after the centrifuge stops naturally. (If hemolysis occurs, blood should be collected again), take the centrifuged upper platelet-rich plasma (PRP), and continue to centrifuge the PRP (1200×g, 10min) to obtain platelets; then use Ca-free solution containing EGTA0.2mmol / L 2+ Wash twice with bench-top solution, and then s...

Embodiment 2

[0028] Example 2 After the nicotinamide mononucleotide phosphoribosyltransferase inhibitor inhibits the activity of nicotinamide mononucleotide phosphoribosyltransferase, the aggregation of platelet-rich plasma is reduced

[0029] Firstly, platelet-rich plasma was separated, and the process was basically the same as in Example 1. Then add the nicotinamide mononucleotide phosphoribosyltransferase inhibitor FK866 (compound CAS number 201034-75-5, obtained by Switzerland Apoxis company) of different concentrations, respectively low (50nM), middle (100nM), high ( 500nM) three concentrations, incubated for 30 minutes. As a solvent control, DMSO (dimethyl sulfoxide) was administered. Add 5M ADP to promote platelet aggregation. Repeat each group 8 times.

[0030] The results are shown in Table 1 and figure 2 As shown, the results show that once nicotinamide mononucleotide phosphoribosyltransferase is inhibited, the coagulation function of platelets is greatly reduced; thus it is...

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Abstract

The invention discloses an application of a nicotinamide mononucleotide ribose phosphate transferase inhibitor. The nicotinamide mononucleotide ribose phosphate transferase inhibitor can effectively prevent or treat thrombocyte hyperfunction, and blood hypercoagulative state or thrombi, has the advantages of favorable curative effect, small side effect and high safety, and has an important meaning for treating coagulation hyperfunction diseases.

Description

technical field [0001] The invention relates to the application of nicotinamide mononucleotide phosphoribosyltransferase inhibitor. Background technique [0002] The coagulation system has two subsystems, procoagulant and anticoagulant, and the weakening or strengthening of either of the two subsystems will cause the coagulation system to lose its balance. Hypercoagulable state of blood refers to the state of increased blood coagulation and easy formation of thrombus, which is called "hypercoagulable state" in English. Although patients with blood hypercoagulability have no symptoms of heart and cerebrovascular infarction clinically, they are at risk of thromboembolism at any time, which is a serious potential risk. There are also some synonyms for hypercoagulable state, such as hypercoagulable state, thrombosis, prethrombotic state, and prethrombotic state. It has an important relationship with the occurrence and development of many diseases, such as deep vein thrombosis,...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/4545A61P7/02A23L1/30A23L33/10
Inventor 缪朝玉王培柯森方
Owner SECOND MILITARY MEDICAL UNIV OF THE PEOPLES LIBERATION ARMY
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