Targeted TRPML1 anti-tumor effect for regulating autophagy

• Main Authors: LIU YUCHENG, SUN CHENLIN, NIE XIAOYA, LI YUNHAN, WANG XINYAN, DING GUYANG
• Format: Patent
• Language: Chinese; English
• Published: 28.07.2023
• Subjects: BEER; BIOCHEMISTRY; CHEMISTRY; COMPOSITIONS OR TEST PAPERS THEREFOR; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL ORENZYMOLOGICAL PROCESSES; ENZYMOLOGY; HUMAN NECESSITIES; HYGIENE; INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIRCHEMICAL OR PHYSICAL PROPERTIES; MEASURING; MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEICACIDS OR MICROORGANISMS; MEDICAL OR VETERINARY SCIENCE; METALLURGY; MICROBIOLOGY; MUTATION OR GENETIC ENGINEERING; PHYSICS; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; PROCESSES OF PREPARING SUCH COMPOSITIONS; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS; SPIRITS; TESTING; VINEGAR; WINE

The invention relates to the technical field of medical biology, and particularly discloses an anti-tumor effect of regulating autophagy by targeting TRPML1, which comprises the following processes: S1, activating TRPML1; s2, tumor cell autophagy downstream blocking; s3, the mitochondrial renewal is impaired, and the damaged mitochondria S4, raising the ROS level; s5, DNA is damaged, and p53 activity is activated; s6, tumor cell apoptosis is triggered, tumor cell metastasis is inhibited, human melanoma cell line A-375 and human glioblastoma cell line U-87MG are selected as tumor cells, a specific small molecule agonist ML-SA5 and an inhibitor ML-SI3 of the TRPML1 are adopted for TRPML1 autophagy activity regulation, the TRPML1 serves as an entry point, the specific small molecule agonist ML-SA5 of the TRPML1 is used for regulating the autophagy activity, and the tumor cell metastasis is inhibited. It is found that in-vitro migration and invasion of human melanoma and glioma can be inhibited through TRPML1 med