7 results about "PIN1" patented technology

The invention relates to a Pin1 protein targeted antagonistic polypeptide, a targeted antagonistic polypeptide nano-micelle as well as a preparation method and application of the targeted antagonistic polypeptide nano-micelle. The Pin1 protein targeted antagonistic polypeptide comprises a targeted antagonistic polypeptide and a cell-penetrating peptide which are connected in sequence, the amino acid sequence of the targeted antagonistic polypeptide comprises any one of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4 or SEQ ID NO: 5; the amino acid sequence of the cell-penetrating peptide comprises SEQ ID NO: 6. The Pin1 protein targeted antagonistic polypeptide can efficiently cross cell membranes and nuclear membranes, is specifically combined with the Pin1 protein in human metastatic pancreatic adenocarcinoma cells, antagonizes the biological function of the Pin1 protein and kills tumor cells. Meanwhile, the Pin1 protein targeting antagonistic polypeptide is combined with gemcitabine, so that the sensitivity of a mixed in-situ tumor model of human metastatic pancreatic adenocarcinoma cells and cancer-related fibroblasts to gemcitabine can be enhanced, the anti-cancer effect of a single drug is amplified, and the anti-tumor effect of 1 + 1 > 2 is generated.

The invention discloses a nano material for specifically promoting PIN1 endocytosis. The nano material can specifically promote PIN1 protein to enter a cytoplasm region from a cytoplasmic membrane region. The invention specifically discloses a structure (formula (I)) of SPc and application of SPc or pharmaceutically acceptable salt thereof in promoting membrane protein internalization of PIN1 protein of a tested plant. The PIN1 protein at the root of arabidopsis thaliana can be promoted to enter a cytoplasm region from a cytoplasm membrane region by applying SPc to arabidopsis thaliana. The PIN1 protein can be used as a positive inducer for researching a PIN1 protein endocytosis related metabolic pathway, and can be used for industrial production.

The present invention provides: a compound represented by the following Formula (I) or a salt thereof, as well as a Pin1 inhibitor, a pharmaceutical composition, a therapeutic or prophylactic agent for inflammatory diseases, a therapeutic or prophylactic agent for fatty liver diseases, a therapeutic or prophylactic agent for obesity, and a therapeutic or prophylactic agent for COVID-19 that utilize the aforementioned compounds or the salts thereof to develop a group of novel compounds with an inhibitory activity against the function of Pin1 so as to use them as candidate compounds for medicaments.

The invention belongs to the field of medicinal chemistry, and discloses a pyrimidine Pin1 covalent inhibitor with a novel structure, and a preparation method, a pharmaceutical composition and application thereof. Specifically, the invention relates to a pyrimidine compound with a new structure as shown in a formula I, a pharmaceutically acceptable salt thereof, a preparation method of the pyrimidine compound, a composition containing one or more of the compounds, and application of the compounds in inhibition of Pin1-related diseases and in preparation of drugs for prevention and / or treatment of neuropsychiatric system diseases and cancers.

The application relates to a construction method of a biomimetic nano-drug delivery system based on a PD1 engineered cancer cell membrane, which comprises the following steps: preparing a nanoparticle inner core of a Pin1 inhibitor by using PLGA, and assisting with fluorescent labeling; engineering PD1 expression on a cancer cell, extracting a PD1-rich cell membrane, and wrapping and modifying API-1-NPs with the PD1 engineered cancer cell membrane to obtain composite nanoparticles API-1@PD1-CCNPs, which can not only guarantee stability and long-term circulation in the delivery process, but also can track the process of the carrier being quickly and effectively targeted to tumor cells and organs in the body in real time, and once internalized by the cancer cell, the wrapped drug API-1 can be effectively released and play a role to inhibit the Pin1 function; the composite nanoparticles API-1@PD1-CCNPs can effectively down-regulate the protein levels of MYC and PD-L1 in hepatocarcinoma cells, thereby effectively synergistically reprogramming the tumor immune microenvironment and affecting tumor immune escape.

This disclosure provides a pharmaceutical combination for treating non-small cell lung cancer, comprising a therapeutically effective amount of a PIN1 inhibitor and a therapeutically effective amount of neratinib.