14 results about "Myc proteins" patented technology

Provided are a c-Myc protein inhibitor, and a preparation method therefor and use thereof. The c-Myc protein inhibitor selectively inhibits c-Myc protein. Therefore, the inhibitor can be used for prevention and treatment of diseases related to c-Myc protein disorders, such as cancers, cardiovascular and cerebrovascular diseases, diseases related to virus infection.

The application discloses a stapled peptide compound for selectively degrading MYC protein, a preparation method and application thereof; the compound is sequentially connected in the N-terminal to C-terminal direction by a peptide recognition segment, a flexible linker and a chaperone-mediated autophagy recognition motif KFERQ or a similar motif; the peptide recognition segment is introduced by an (i, i+7) site alkenyl amino acid and a Grubbs catalytic RCM reaction to form a full carbon hydrogen stapling bridge to stabilize the alpha-helix conformation; stapled modification of a typical compound MAX-7 significantly improves the alpha-helix content, the protease stability and the cell penetration, so that the compound can efficiently enter cells and be located in lysosomes, and MYC protein is selectively degraded through the CMA pathway; in-vitro experiments show that MAX-7 can inhibit the proliferation, migration and invasion of various MYC-driven tumor cells, and induce apoptosis; the application provides a brand-new lysosome-directed degradation strategy for the "undruggable" target MYC, and establishes a universal technical platform which can be popularized to other difficult drug proteins.

Disclosed are substituted heterocyclic compounds and proteolysis-targeting chimeric molecules (PROTACs). The substituted heterocycles disclosed herein are shown to be useful in inhibiting c-MYC. The disclosed PROTACs are shown to induce degradation of c-MYC protein. The substituted heterocyclic compounds and proteolysis-targeting chimeric molecules (PROTACs) disclosed, herein may be utilized as therapeutics for treating cancer and cell proliferative disorders.

The present invention relates to a protein degradation agent, a preparation method therefor, and a use thereof. The protein degradation can degrade various proteins including c-Myc protein, and therefore can be used for prevention and treatment of diseases related to disorders of various proteins including c-Myc protein, such as cancer; cardiovascular and cerebrovascular diseases, and viral infection-related diseases.

The application discloses application of YW2301 in preparation of a medicine for resisting Burkitt lymphoma, utilizes CCK8 cell activity experiment to detect the inhibition ability of YW2301 on Raji and CA46 cell proliferation, constructs a NON / SCID subcutaneous transplantation tumor model by using a Raji cell line, evaluates the therapeutic significance of YW2301 on Burkitt lymphoma, YW2301 can effectively inhibit the tumorigenicity of Burkitt lymphoma cells and the growth speed of the transplantation tumor, and adopts immunohistochemical staining to detect the ALDH18A1 and c-Myc protein expression in a Burkitt lymphoma transplantation tumor tissue section, YW2301 can effectively down-regulate the ALDH18A1 and c-Myc protein expression in a Burkitt lymphoma tissue, and further proves that YW2301 can be used as a candidate small molecule for targeted treatment of Burkitt lymphoma.

The invention discloses application of circZFAND6 as a target spot in preparation of a product for treating ovarian cancer, and belongs to the technical field of biological medicine. The invention discloses a key action mechanism of circZFAND6 derived from TAMs exosome in the occurrence and development of the ovarian cancer. After the exosome circZFAND6 secreted by the TAMs is over-expressed and is taken by the ovarian cancer cells, the proliferation, migration and invasion capabilities of the cancer cells can be remarkably promoted; knock-down can effectively inhibit the malignant biological behaviors. According to the circZFAND6, the stability of c-Myc protein is maintained, glycolysis key enzyme expression regulated and controlled by c-Myc is up-regulated, the Warburg effect is enhanced, and the malignant progression of ovarian cancer is accelerated. The invention not only provides a solid theoretical basis and experimental evidence for the therapy strategy of the targeted circZFAND6 ovarian cancer, but also opens up a new direction for the intervention research of tumor metabolism reprogramming.

The invention belongs to the technical field of biological medicines, and particularly relates to application of an MYC mRNA translation inhibitor in preparation of a medicine for preventing and / or treating osteoarthritis. The MYC mRNA translation inhibitor is selected from biological materials capable of inhibiting or blocking the MYC mRNA translation process, reducing the MYC protein synthesis efficiency or interfering the MYC mRNA steady state level. The invention provides a novel molecular target capable of being used for treating osteoarthritis and a medicine application scheme of the molecular target.

The application discloses a kind of preeclampsia (Preeclampsia, PE) diagnosis and treatment biology marker and its application;The application is from clinical sample, cell and in-depth demonstration of overexpressed FBP2 at the level of body, which causes the mechanism of PE occurrence by inhibiting the invasion of trophoblasts, and the application verifies that the classic gene HEY1 downstream of NOTCH3 can be combined with the promoter region of FBP2 and transcribe to inhibit the expression of FBP2, FBP2 is combined with c-MYC protein and inhibits the transcriptional activity of c-MYC, down-regulates the transcriptional expression of TFAM, causes mitochondrial dysfunction, weakens the migration and invasion ability of trophoblasts, participates in the mechanism of PE occurrence, is a new mechanism clue obtained according to the results of pre-experiment and information analysis, is a new target for in-depth exploration of PE clinical diagnosis and treatment, and the research results can provide theoretical basis for guiding early prediction and intervention of PE in the future.

Disclosed is a compound as shown in general formula I or a pharmaceutically acceptable salt, tautomer, mesomer, racemate, enantiomer, and diastereomer thereof. The compound of the present invention significantly improves the degradation effect of GSPT1 protein and the anti-proliferative inhibition activity of AML and solid tumor cells. Therefore, the compound of the present invention can be used in the preparation of a medicament for treating or preventing diseases related to GSPT1, IKZF1, IKZF2, IKZF3, CK1α, N-MYC or C-MYC protein mutation, expression imbalance, and allostery and functional abnormalities; in addition, said compound can be used to prepare a GSPT1 degrading agent.

The application discloses a kind of gastric adenocarcinoma transgenic mouse model construction method and its application, the construction method includes the following steps: using transgenic and hybridization technology, MYC gene expression quantity or MYC protein activity in mouse gastric mucosa layer epithelial cell is overexpressed or increased, KRAS gene mutant type in gastric mucosa layer epithelial cell is activated simultaneously, make Kras protein function abnormal, continuously in activated state, finally obtained mouse is gastric adenocarcinoma transgenic mouse model.The application constructs Myc gene overexpression and KRAS activation mutation double gene mutation mouse spontaneous gastric cancer animal model, method is simpler.This mouse model of gastric cancer tumorigenesis time is shortened, tumorigenic rate is as high as 100%, and tumorigenic effect is stable.And after induction, only in stomach tumorigenesis, tumorigenesis has high specificity.Pathological section and immunohistochemical staining determine that this animal model is adenocarcinoma in gastric cancer, has good clinical representativeness, can be applied to the application in later development or screening gastric cancer drug.

The application discloses a small molecule degrading agent of aryl formamides and application thereof, and has a structure shown in general formula I or a pharmaceutically acceptable salt, an isotopically labeled compound thereof. The compound of the application has a targeted degradation activity on MYC protein, and has a significant proliferation inhibiting activity on various solid tumor cells such as neuroblastoma and rhabdomyosarcoma. The compound of the application can be used for preparing a degrading agent targeting MYC protein, and can also be used for preparing a drug for treating diseases related to MYC gene amplification, fusion, mutation, expression imbalance, conformational change and function abnormality.

The application provides an isolated polypeptide and application thereof, and the polypeptide comprises an amino acid sequence shown in SEQ ID NO: 2 or an amino acid sequence with at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identity with the amino acid sequence shown in SEQ ID NO: 2. The isolated polypeptide can specifically bind to a c-Myc protein, destroy the stabilizing effect of RALY on the c-Myc protein, promote the degradation of the c-Myc protein through a ubiquitin-proteasome pathway, inhibit the proliferation of cancer cells, reduce the survival ability of the cancer cells, and can effectively prevent and / or treat tumors.

This present disclosure relates to methods and compositions comprising biologically active nanoparticle formulations of MYC protein. Provided are methods of making the nanoparticle formulations and methods of using the nanoparticle formulations for treatment.

The invention relates to the technical field of biological medicines, and relates to application of circPTK2 as a marker in preparation of a product for bladder cancer diagnosis or prognosis. Researches show that the CAFs-derived exosome can deliver circPTK2 to bladder cancer cells, the circPTK2 can be combined with C-Myc protein and promote nuclear translocation of the C-Myc protein, then expression of C-Myc downstream Warburg effect related proteins GLUT1 and LDHA is regulated and controlled, and migration, invasion and lymph node metastasis of the bladder cancer cells are affected. Meanwhile, the circPTK2 level in serum and urine exosomes is closely related to prognosis and lymphatic metastasis of bladder cancer patients and can be used as an effective marker for diagnosis and prognosis of bladder cancer and prediction of lymphatic metastasis, and a new thought and tool are provided for clinical diagnosis and treatment of bladder cancer.