11 results about "DU145" patented technology

The invention discloses application of a small molecular compound secalonic acid B in inhibiting Skp2 protein and resisting prostate cancer cell metastasis, and belongs to the technical field of medicines. The research finds that secalonic acid B can obviously reduce the half-life period of Skp2, accelerate the degradation speed of Skp2 and reduce the protein level of Skp2 in DU145 cells by enhancing the polyubiquitination process on Skp2 protein. The secalonic acid B induces proteasome degradation of Skp2 through a multi-ubiquitination pathway of a K48 chain, so that tumor cell metastasis is inhibited, and the effect of resisting prostatic cancer is achieved. The invention discloses an action mechanism of secalonic acid B in inhibiting Skp2 protein and resisting prostate cancer cell metastasis, lays a theoretical foundation for research and development of drugs for inhibiting Skp2 protein and treating prostate cancer, and provides a new strategy for treatment of prostate cancer.

The invention discloses a double-target chimeric antigen receptor capable of simultaneously targeting TLL1 and B7H3, a CAR-T cell and application of the double-target chimeric antigen receptor. The chimeric antigen receptor is a fusion protein which is sequentially composed of Omburt-scFv (SEQ ID NO: 1) targeting B7H3, a CD8 alpha hinge region and transmembrane region, a 4-1BB costimulatory domain, a CD3 zeta signal domain and TLL1-scFv (SEQ ID NO: 6) targeting TLL1 from an N terminal to a C terminal. The TLL1-scFv can be efficiently combined with TLL1 protein, can inhibit a TGF-beta signal channel and block prostate cancer cell migration, and is integrated into CAR of targeted B7H3, so that the double-target CAR-T cell with direct killing and immune microenvironment regulation functions is successfully constructed. The CAR-T cell has a remarkable killing effect on a prostate cancer cell line DU145, can be strongly activated after being co-cultured with a target cell and secretes a large amount of IFN-gamma and TNF-alpha, and shows high immunocompetence. The invention provides a new synergistic immunotherapy strategy for the B7H3-positive prostate cancer with the TGF-beta signal channel activated.

The present invention belongs to the field of biochemistry and discloses a polypeptide comprising: (I) an amino acid sequence as shown in SEQ ID No. 1; or (II) an amino acid sequence formed by adding one or more amino acids before or after the amino acid sequence as shown in (I); or (III) a cell-penetrating polypeptide obtained by combining the polypeptide shown in (I) or (II) with a cell-penetrating peptide. The polypeptide significantly inhibits the growth and proliferation of two prostate cancer cell lines (DU145 and PC3), as well as RNA alternative splicing. The present invention also discloses a drug containing the polypeptide and its uses.

The application discloses application of a traditional Chinese medicine monomer, syringa pubescens A, in preparation of a medicine for resisting prostate cancer. The application proves through experiments that syringa pubescens A can inhibit the proliferation, migration and invasion of DU145 cells and promote cell apoptosis by down-regulating the expression of Atox1 protein and activating the activity of a copper death signal pathway. Based on the above discovery, syringa pubescens A has an anti-tumor effect on DU145 cells and can be used as a potential candidate medicine for resisting prostate cancer, thereby providing a new medicine selection for the treatment of prostate cancer.

The invention belongs to the technical field of biological medicines, and provides an imide aryl piperazine derivative as well as a preparation method and application thereof. The imide aryl piperazine derivative with the structure as shown in the formula (I) provided by the invention shows that the imide aryl piperazine derivative has relatively strong cytotoxicity to PC-3, LNCaP and DU145 cancer cells and human normal prostate epithelial cells in experiments of toxicity to the PC-3, LNCaP and DU145 cancer cells, but shows weak activity and high selectivity to the human normal prostate epithelial cells; the compound can be further used as an anti-prostatic cancer treatment candidate drug with an excellent effect.

This invention relates to the field of biopharmaceutical technology, and in particular to the application of myrotoxin A in the preparation of drugs for treating prostate cancer. This invention is the first to discover the function of myrotoxin A in inducing ferroptosis in DU145 prostate cancer cells by targeting and inhibiting ACSL3 protein, and its inhibitory effect on prostate cancer proliferation. Specific embodiments of this invention reveal for the first time that myrotoxin A can precisely utilize the unique metabolic vulnerability of prostate cancer cells, significantly downregulating the expression of ACSL3 protein in DU145 cells at the protein level. This, in turn, by relieving the inhibition of ferroptosis by ACSL3 protein, specifically induces ferroptosis in prostate cancer cells, ultimately effectively inhibiting tumor cell growth and achieving the therapeutic goal of targeting prostate cancer development.

The application discloses an application of an indole dione piperazine compound in preparation of a drug for resisting prostate cancer. Experiments such as MTT, flow cytometry, protein chip, molecular docking, CETSA, transmission electron microscopy and zebra fish model prove that the compound significantly inhibits proliferation of prostate tumor cells such as PC-3, 22Rv1 and DU145, blocks division of PC-3 cells in the G1 phase, and induces apoptosis and necrotic apoptosis of PC-3 cells; the mechanism is that the compound directly combines NQO1 and NRF2, activates the HO-1 / NRF2 / NQO1 pathway, promotes excessive generation of ROS, and causes NQO1-dependent oxidative stress. The zebra fish model in vivo shows that the compound inhibits growth of prostate tumors. The application provides a lead compound with a new mechanism for preventing and treating prostate cancer and potential for overcoming drug resistance.

The invention belongs to the technical field of prostate cancer diagnosis, and particularly relates to serum 7-dehydrocholesterol as a prostate cancer metastasis and endocrine treatment drug resistance diagnosis marker and application thereof. 7-dehydrocholesterol provided by the invention has different levels in human prostate cancer cell lines such as LNCaP, Du145, PC3 and the like, and is abnormally increased in PC3, so that the 7-dehydrocholesterol can be used as a drug resistance diagnosis marker for prostate cancer metastasis and endocrine therapy; the reagent composition capable of specifically recognizing 7-dehydrocholesterol and generating detectable signals can be used for preparing a prostate cancer detection kit; the 7-dehydrocholesterol provided by the invention has non-invasive, non-invasive and efficient effects as a diagnostic marker, and solves the technical problem of lack of a prostate cancer diagnostic marker in the prior art.

The invention relates to BRD4 and p300 / CBP double-target PROTAC molecules as well as a preparation method and application thereof, and belongs to the technical field of medicinal chemistry. The compound has a general formula shown in the specification, wherein L is preferably selected from one of the group; and E is preferably selected from one of the group. The compound disclosed by the invention has remarkable anti-tumor activity on human prostatic cancer cell strains PC-3, DU145 and 22Rv1 in vitro, the IC50 values are all lower than 20nM, and particularly, the IC50 values are all lower than 10nM in the cells PC-3 and DU145. The compound I-c shows the optimal activity, the IC50 values of the compound I-c in PC-3 and DU145 cells are 2.80 nM and 6.62 nM respectively, and the IC50 values of the compound I-c are obviously superior to those of positive control drugs NEO2734, paclitaxel and ARV-771. As a novel BRD4 and p300 / CBP double-target PROTAC molecule, the compound disclosed by the invention has a definite action mechanism and excellent anti-tumor activity, and can be used as a candidate or lead compound for research and development of anti-tumor drugs; the synthesis method is simple and convenient, and has good popularization and application prospects.

The application discloses a combined drug for treating prostate cancer and application, the combined drug is a combined drug of FEN1-IN-4 and TRi-1 administered respectively or simultaneously, the FEN1-IN-4 is an inhibitor targeting Flap endonuclease 1, and the TRi-1 is an inhibitor targeting thioredoxin (TXN) antioxidant system.The combined treatment scheme of FEN1-IN-4 and TRi-1 provided by the application firstly shows a strong antitumor effect superior to single drug in vitro experiment.FEN1-IN-4 as FEN1 specific inhibitor can block the endonuclease function of FEN1 by combining with the active site of FEN1, and can achieve significant growth inhibition to various prostate cancer cell lines such as LNCaP, 22RV-1, PC3, DU145, and the like, and TRi-1 as TXN antioxidant system inhibitor can target to destroy the oxidative stress balance of tumor cells, and the two act on different key pathways (DNA replication / damage repair pathway and antioxidant defense pathway) of tumor cells, forming a "double targeting" synergistic effect.

The invention discloses a combined medicine for treating prostatic cancer and application, the combined medicine is a combined medicine of FEN1-IN-4 and TRI-1 which are respectively or simultaneously administered, the FEN1-IN-4 is an inhibitor of a targeted Flap endonuclease 1, and the TRI-1 is an inhibitor of a targeted thioredoxin (TXN) antioxidant system. According to the combined treatment scheme of FEN1-IN-4 and TRI-1 provided by the invention, firstly, a strong anti-tumor effect superior to that of a single drug is shown in an in-vitro experiment; the FEN1-IN-4 serving as a FEN1 specific inhibitor can block the endonuclease function of the FEN1 active site by combining the FEN1 active site and can achieve remarkable growth inhibition on various prostate cancer cell lines such as LNCaP, 22RV-1, PC3 and DU145, and the TRI-1 serving as a TXN antioxidant system inhibitor can achieve remarkable growth inhibition on various prostate cancer cell lines such as LNCaP, 22RV-1, PC3 and DU145. Oxidative stress balance of tumor cells can be damaged in a targeted mode, and the two functions on different key pathways (a DNA replication / damage repair pathway and an anti-oxidation defense pathway) of the tumor cells to form a dual-targeting synergistic effect.