M2 type pyruvate kinase small molecule activator and application thereof

Abstract

The invention provides a small molecular activator taking human M2 type pyruvate kinase (M2 type pyruvate kinase, PKM2) as a target spot and application of the small molecular activator, and belongs to the technical field of pharmacy. According to the small molecular activator, the PKM2 is taken as the target spot, and the small molecule activator is screened by combining virtual screening based on butt joint and in-vitro biological activity evaluation. In-vitro activity test results show that two screened compounds have good PKM2 activation activity and good cancer cell inhibition activity, and discovered small molecules can provide a basis for research and development of new drugs for treating PKM2 related diseases, such as cervical cancer, breast cancer, ovarian cancer, prostate cancer,liver cancer, lung cancer, pancreatic cancer, colorectal cancer, leukemia, melanoma and multiple myeloma. A lead compound of the small molecular activator can be further optimized in structure, and arelatively good application prospect is achieved.

Description

technical field [0001] The invention belongs to the technical field of medicinal chemistry, and specifically relates to the application of a lead compound for activating human PKM2 kinase activity by targeting M2 type pyruvate kinase (PKM2) protein in the preparation of PKM2-related disease drugs. Background technique [0002] In cells, the process of metabolizing glucose into lactic acid is called glycolysis, and the reaction process can be divided into two stages; the first stage is called glycolytic pathway, which is the process of decomposing glucose into pyruvate ; The second stage is the process of converting pyruvate into lactic acid. The last step in the glycolytic pathway is catalyzed by pyruvate kinase (Pyruvate Kinase, PK), which transfers phosphate from phosphoenolpyruvic acid (PEP) to adenosine diphosphate , ADP), thus producing pyruvate and ATP. [0003] Tumor cells take up and metabolize nutrients differently from normal cells, which provides a possible stra...

AI Technical Summary

Problems solved by technology

However, the types and quantities of PKM2 agonists that have been reported are still quite limited, and it is still necessary to design and discover activators that specifically target PKM2 with a new backbone.

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