23 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.

Vectors and methods are disclosed for immortalizing mammalian cells by co-expression of v-raf and v-myc proteins. A replication-defective viral vector is used for improved safety. The vector comprises an optional marker gene, and is especially useful for producing an immortalized macrophage by a method that involves contacting the vector with a monocyte, proliferatively growing the monocyte, growing the monocytic cell on a solid surface, and then growing the monocytic cell on a porous surface. An immortalized macrophage is also disclosed.

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 invention relates to the technical field of biological medicine, and discloses application of an MYC inhibitor in preparation of a BET inhibitor sensitizing drug. In order to screen a synergistic drug of a BET inhibitor, a core transcription factor for regulating a super enhancer (SE) is systematically screened, and it is found that MYC is a core main transcription factor of a tumor SE regulation network. Furthermore, experiments prove that the cancer inhibition effect of the BET inhibitor can be remarkably improved and the effective concentration of the BET inhibitor can be reduced by inducing and degrading endogenous MYC protein, inducing expression of negative dominant inhibition polypeptide Omomyc of MYC or treating with an MYC small-molecule inhibitor. Therefore, the MYC inhibitor can be used as a BET inhibitor sensitizing drug, and has a relatively good application prospect.

The invention provides a c-Myc protein targeting degradation agent and a preparation method and application of a nano-selenium coupled polypeptide drug, and belongs to the technical field of biological medicines. The amino acid sequence of the degradation agent is shown as SEQ ID NO: 1, the binding constant of the degradation agent and c-Myc protein is 40.18 nM, and it is indicated that the degradation agent has high binding capacity with the c-Myc protein. The degradation agent or the polypeptide drug coupled with the nano-selenium is delivered into tumor cells, c-Myc protein can be effectively degraded, and the capability of remarkably inhibiting tumor growth and inducing tumor cell apoptosis is shown. Therefore, the preparation method of the degradation agent or the polypeptide drug coupled with nano-selenium can be applied to preparation of drugs for preventing and / or treating c-Myc protein disorder related diseases such as tumors or preparation of reagents for degrading c-Myc protein, and has very wide application value and patent medicine prospect.

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.

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.

A substituted heterocyclic compound and a proteolysis-targeting chimera molecule (PROTAC) are disclosed. The substituted heterocycles disclosed herein are shown to be useful for inhibiting c-MYC. The disclosed PROTACs have been shown to induce the degradation of c-MYC protein. The substituted heterocyclic compounds and proteolysis-targeting chimera molecules (PROTACs) disclosed herein can be utilized as therapeutic agents for treating cancer and cell proliferative disorders.

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 invention relates to application of a compound Y500-3645 as a c-Myc protein degradation agent in preparation of a drug for resisting multiple myeloma, and belongs to the technical field of multiple myeloma. The pharmaceutical composition for treating multiple myeloma provided by the invention takes a compound shown as a formula Y500-3645 or pharmaceutically acceptable salt thereof as an active ingredient or a main active ingredient, and is supplemented with a pharmaceutically acceptable carrier. In multiple myeloma, the compound Y500-3645 inhibits the expression of c-Myc by promoting the degradation of c-Myc protein, regulates the expression levels of mRNA and protein of related genes, and promotes the death of myeloma cells. As a drug for resisting multiple myeloma, a new thought is provided for research and development of the drug for resisting multiple myeloma. # imgabs0 #

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 invention belongs to the technical field of medicines, and particularly relates to syringin targeted inhibition DLAT protein and application of syringin targeted inhibition DLAT protein in inhibition of mycobacterium tuberculosis. Research finds that natural micromolecule syringin can inhibit DLAT protein activity in a targeted manner, reduce acetylation of MYC protein and promote ubiquitination and degradation of MYC protein, so that the MYC protein level is reduced, M2 type polarization of macrophages is inhibited, the polarization state of the macrophages is adjusted, growth of mycobacterium tuberculosis in the macrophages is inhibited, and the MYC-MYC-MYC-MYC-MYC-MYC-MYC-MYC-MYC-MYC is inhibited. The anti-tuberculosis effect is effectively achieved. Compared with an existing anti-tuberculosis technology, the anti-tuberculosis scheme is clear in action mechanism and accurate in targeting effect, and blindness of a traditional therapy is avoided. According to the present invention, the tuberculosis condition can be effectively controlled, the treatment period is expected to be shortened, the physical, mental and economic burden of the patient is reduced, the untoward effect risk is substantially reduced due to the high biological safety of the natural small molecules, and the new reliable path is provided for the clinical anti-tuberculosis treatment.

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 present invention discloses the application of the YOD1 gene in the preparation of a drug for treating rhabdomyosarcoma. The present invention deeply analyzes how YOD1 co-regulates the stability of PAX3-FOXO1 and N-Myc proteins. After inducing and reducing YOD1 expression using a tetracycline regulatory system, the cloning ability and xenograft tumor growth of rhabdomyosarcoma cells that are FOXO1 fusion-positive and accompanied by high N-Myc expression are significantly inhibited. Therefore, the present invention not only discloses the application of the YOD1 gene, but also provides a new therapeutic target for rhabdomyosarcoma cells that are FOXO1 fusion-positive and accompanied by high N-Myc expression.

This invention relates to the field of biopharmaceuticals and discloses the use of MYC inhibitors in the preparation of drugs that enhance BET inhibitor sensitization. To identify synergistic agents with BET inhibitors, the present invention systematically screened for core transcription factors regulating super-enhancers (SEs) and discovered that MYC is a core master transcription factor in the tumor SE regulatory network. Furthermore, the present invention experimentally demonstrated that inducing degradation of endogenous MYC protein, inducing expression of the dominant-negative MYC inhibitor peptide Omomyc, or treating with a MYC small molecule inhibitor significantly enhances the tumor suppressor effect of BET inhibitors and reduces their effective concentration. Therefore, MYC inhibitors can be used as BET inhibitor sensitizers and have promising application prospects.

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.