Application of imidazo quinazoline compound in preparation of medicine for treating KRAS mutation gastrointestinal tumor

Imidazoloids and quinazoline compounds inhibit the binding of p-ERK2 to p53, restore p53 transcriptional activity, and selectively inhibit KRAS-mutant gastrointestinal tumor cells, thus solving the problems of poor targeting and drug resistance in existing technologies and achieving highly efficient tumor suppression.

CN122140720APending Publication Date: 2026-06-05KUNMING MEDICAL UNIVERSITY
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Patent Information

Application Number
CN202610624193.0
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Filing Date
2026-05-08
Publication Date
2026-06-05

AI Technical Summary

Technical Problem

Current technologies lack small molecule inhibitors that can specifically target the p-ERK2-p53 complex, resulting in poor treatment outcomes for KRAS-mutant gastrointestinal tumors. In particular, the proportion of KRAS G12C mutations is low and they are not sensitive to existing inhibitors, while drug resistance is common in mutation subtypes such as G12D, G12V, and G13D.

Method used

To develop imidazoquinaline small molecule compounds or their pharmaceutically acceptable salts, which can selectively inhibit the proliferation, migration and invasion of KRAS-mutant gastrointestinal tumor cells by restoring the transcriptional activity of p53 through inhibiting the binding of p-ERK2 to p53.

Benefits of technology

Imidazolidine compounds exhibit significant selective inhibitory activity against KRAS-mutant gastrointestinal tumors, with an in vitro IC50 of approximately 0.42 μM and IC50s of 45.92 μM and 41.27 μM for KRAS wild-type cells, respectively, representing a selectivity index of approximately 100-fold. The in vivo tumor inhibition rate reached 87.56%, and the safety profile was good.

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Abstract

The invention belongs to the technical field of biological medicine, and particularly relates to application of imidazo quinazoline small molecule compounds shown in the formula (I) or pharmaceutically acceptable salts thereof in preparation of drugs for treating KRAS mutation gastrointestinal tumors, and R is described in the claims and the specification. The imidazo quinazoline compound can selectively inhibit proliferation, migration and invasion of KRAS mutation gastrointestinal tumor cells and induce cell cycle arrest and apoptosis. Specifically, by inhibiting the combination of p-ERK2 and p53, the compound recovers the transcriptional activity of p53 and up-regulates the expression of p53 downstream papoptosis-promoting gene PUMA, thereby playing an anti-tumor role. The action mechanism is different from that of a traditional KRAS or MEK inhibitor, and a new treatment choice is provided for patients with KRAS mutation gastrointestinal tumors.
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