187 results about "Myeloid leukemia" patented technology

This invention relates to pharmaceutical compositions, pharmaceutical combinations and methods for the treatment of acute myeloid leukemia by combined use of a therapeutically effective combination of a compound of Chemical Formula 1, or a pharmaceutically acceptable salt thereof, solvate thereof, stereoisomer thereof, tautomer thereof, or combination thereof, wherein Ea, Eb, Ec, Ed, Z′, X′, Q, and k are defined herein; and a Bcl-2 inhibitor, or a Bcl-2 inhibitor and a hypomethylating agent.

The invention provides a VEGFR2-HDAC6 dual inhibitor containing chalcone fragments as well as a preparation method and application of the VEGFR2-HDAC6 dual inhibitor, and relates to the technical field of medicinal chemistry. The invention discloses a VEGFR2-HDAC6 dual inhibitor containing chalcone fragments. The structural formula of the VEGFR2-HDAC6 dual inhibitor is shown as a formula A, according to the invention, the VEGFR2-HDAC6 dual inhibitor containing the chalcone fragment and having a novel structure is designed and synthesized by utilizing a splicing principle, the anti-proliferative activity test is carried out on cervical cancer cells Siha and chronic granulocytic leukemia cells K562, and the result shows that the VEGFR2-HDAC6 dual inhibitor containing the chalcone fragment provided by the invention has relatively good inhibitory activity on the Siha cells and the K562 cells.

The invention relates to the field of molecular targeted therapy, and discloses an application of an SLC16A5 (MCT6) small-molecule inhibitor MCT6-Ai7-2 in preparation of a medicine for treating acute myeloid leukemia (AML). The inhibitor takes an SLC16A5 protein structure predicted by Alphafold as a target spot, and is obtained through compound database screening, molecular docking and druggability optimization. An in-vitro experiment proves that MCT6-Ai7-2 can remarkably inhibit proliferation of AML cell lines such as U937 and MOLM-13, induce cell apoptosis and retard a cell cycle, has an inhibiting effect on a primary AML patient specimen and is relatively low in toxicity to normal cells; in-vivo experiments show that the compound is effective and has good safety in AML model mice. In addition, the MCT6-Ai7-2 and the vinca can be combined to synergistically enhance the inhibition effect on vinca drug-resistant cells, and by reducing the expression of anti-apoptotic protein MCL-1, the activation of pro-apoptotic factors BIM and tBID is promoted to play a role. The invention provides a novel targeting drug and strategy for treatment of AML (especially drug-resistant or recurrent patients).

The present invention includes compositions and methods for retrieving tumor-related antibodies and antigens. In one aspect, the invention includes a method for Sequential Tumor-related Antibody and antigen Retrieving (STAR) which directly and efficiently identifies potent antibodies that can specifically bind to tumor-related antigens on the tumor cell surface. In another aspect, the invention includes a CAR comprising a nanobody, a transmembrane domain, and an intracellular domain, wherein the nanobody is retrieved by a STAR method. In another aspect, the invention includes a CAR T system that targets CD13 and treats acute myeloid leukemia. In another aspect, the invention includes a CAR T system and ADC that targets CDH17 and treats NETs and other types of tumors expressing this antigen, with tolerable toxicities.

The present invention relates to methods of treating hematological malignancies, such as acute myeloid leukemia (AML) or spinal dysplasia syndrome (MDS), including hematological malignancies that are refractory to chemotherapeutic agents and / or demethylating agents. Methods involve administering to a patient a CD123x CD3 bispecific binding molecule in an amount effective to stimulate cells that kill the hematological malignancy in the patient. The invention is further directed to embodiments of such methods in which a cell sample from a patient demonstrates the expression of one or more target genes relative to the baseline expression level of such genes, e.g., in a reference population of individuals suffering from hematological malignancies, such as, for example, the expression level of such genes, e.g., in the reference population of individuals suffering from hematological malignancies, or in the reference population of individuals suffering from hematological malignancies. Or the expression level relative to the reference gene is increased.

The invention belongs to the technical field of chemical medicines, and particularly relates to a diaryl methyl piperazine compound as well as a preparation method, a pharmaceutical composition and application thereof. The structural formula of the diaryl group methyl piperazine compound is shown as a formula I, and R is any one of alkane, cycloalkane and substituted acyl. The preparation method is simple, the diaryl methyl piperazine compound can be prepared in one step, the prepared diaryl methyl piperazine compound or the pharmaceutically acceptable salt thereof has the activity of efficiently inhibiting WDR5-MLL1, and potential drug molecules which are novel in structure, high in drug effect, safe and effective are provided for treating WDR5-MLL1 acute myeloid leukemia.

Some embodiments of the invention include inventive compounds (e.g., compounds of Formula (I), (II), or (III)) and compositions (e.g., pharmaceutical compositions) which inhibit IRAK and / or FLT3 and which can be used for treating, for example, certain diseases. Some embodiments include methods of using the inventive compound (e.g., in compositions or in pharmaceutical compositions) for administering and treating (e.g., diseases such as hematopoietic cancers, myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), etc.). Additional embodiments provide disease treatment using combinations of the inventive IRAK and / or FLT3 inhibiting compounds with other therapies, such as cancer therapies.

The present disclosure features methods for identifying pateints having a hyperproliferative disease, disorder, or condition responsive to phosphodiesterase 3 (PDE3) and schlafen family member 12 (SLFN12) complex formation. The hyperproliferative disease, disorder, or condition may be cancer in a patient including glioblastoma, melanoma, ovarian cancer, cervical cancer, sarcoma, or hematopoietic cancers, such as acute myeloid leukemia. Those responsive diseases, disorders, or conditions may be identified using the biomarker AIP and / or TRRAP in combination with those biomarkers pertinent to phosphodieseterase 3 and schlafen family member 12 complexes which may be formed by PDE3 modulation with certain active compounds. Expression of combinations of these biomarkers have been shown to correlate with active compound (e.g., PDE3 modulator, PDE3A modulator, PDE3B modulator) sensitivity.

The present invention relates to methods and compositions for the treatment of BAF-related disorders such as acute myeloid leukemia.

The invention discloses a method for constructing a human marrow paraffin tissue space transcriptome sequencing map, which comprises the following steps of: obtaining high-quality space transcriptome data from a marrow paraffin section of an AML (acute myeloid leukemia) patient, and then integrating the space transcriptome with scRNA-seq and histopathology. Relatively complete transcriptome information is still preserved after the bone marrow specimen is subjected to better decalcification treatment, and meanwhile, higher-quality slicing treatment can be performed on the embedded paraffin tissue, so that very complete bone marrow space transcriptome sequencing data is obtained. Then, the cell type of each detection site in the bone marrow space transcriptome map can be accurately defined by integrating bone marrow single cell sequencing data and pathological morphology annotations, and subsequent analysis is carried out.

The invention is related to a method of treating a subject with acute myeloid leukemia, acute lymphoblastic leukemia, non-Hodgkin's lymphoma, Burkitt lymphoma, or diffuse large B-cell lymphoma by administration of Compound (I), or a pharmaceutically acceptable salt thereof.

The present invention belongs to the field of biomedicine, and specifically relates to a prognostic model for predicting the overall survival rate of AML patients based on 9 fatty acid metabolism-related genes. The present invention analyzed the gene expression profiles of 354 AML patients from TCGA and VIZOME, determined the prognosis-related genes based on the fatty acid metabolism-related genes of the TCGA dataset using univariate Cox regression analysis and survival analysis, and established a prognostic model with 9 fatty acid-related genes. This model can evaluate the prognosis of AML patients more specifically and sensitively. Then, using a nomogram, the fatty acid metabolism gene prognostic model, age, and cytogenetic risk degree were integrated into a scoring system to more accurately predict the survival of AML patients, with broad clinical application prospects.

This invention discloses the use of plasma exosome-derived miRNA in the preparation of products for the diagnosis and / or prognosis assessment of acute myeloid leukemia. This invention can be used as a prognostic indicator or early diagnosis indicator for AML patients and has promising application prospects in predicting the prognosis or early diagnosis of AML patients.

Provided herein are myeloid leukemia protein 1 (Mcl-1) inhibitors, methods for their preparation, related pharmaceutical compositions, and methods of use thereof. For example, provided herein are compounds of Formula (I), or a stereoisomer thereof, and pharmaceutically acceptable salts thereof, and pharmaceutical compositions containing the compounds. The compounds and compositions provided herein may be used, for example, in the treatment of diseases or conditions, such as cancer.

Genetically modified zebrafish, in which mutation combinations frequently identified in human AML are stably expressed in the stem cell population of the fish, are provided. The combination of mutations result in morphologic, cytochemical and molecular changes of its blood cells that are remarkably similar to those in human AML. The zebrafish model provides a foundation for the study of AML initiation and progression and a high throughput in vivo drug screening platform to identify personalized therapies for AML based on specific mutation combinations. The method of drug screening includes contacting embryos or adult fish containing mutations as disclosed herein, with a test agent, at test concentrations and test intervals to determine the therapeutic effect if any, of the test agent.

The invention belongs to the technical field of gene engineering, and particularly relates to a medicine for treating AML (acute myelogenous leukemia) and / or prognosis of AML patients and application of ubiquitin specific protease 20 serving as a target spot in treating acute myelogenous leukemia. The invention provides a medicine for treating AML (acute myelogenous leukemia) and / or prognosis of an AML patient and application of ubiquitin specific protease 20 as a target spot in treating acute myelogenous leukemia, USP20 is used as a super enhancer regulation gene, and the progress of the AML is promoted by combining with CTNNB1, ERG, ELF1 and RUNX1. The knock-down of the USP20 can significantly inhibit AML proliferation in vivo and in vitro. The wnt-beta-catenin pathway can be influenced by interfering the expression of the USP20 so as to influence the progress of AML (acute myeloid leukemia). And the inhibition effect of the inhibitor AS1517499 subjected to virtual screening on the growth of the AML cells is superior to that of a commercial inhibitor GSK2643943A of USP20.

Methods, compositions, and systems for treating various cancers are disclosed. The disclosed compositions may include a poly peptide with affinity for a CD99 cell surface protein. Disclosed polypeptides may comprise a sequence selected from GYYMH, RINPYTGATTYNQIFKD, YYYGNNYNVYLDY, SASQGISNYLS, YTSTLHIS, and QQYSNLPWT, and may include mouse, human, or humanized peptide sequences. In many embodiments, the polypeptides may be immunoglobulins, for example IgG3 or IgG4. The disclosed polypeptides may be administered to a subject having a cancer cell with elevated expression of CD99. In some embodiments, the subject may be suffering from cancer, including diffuse intrinsic pontine glioma (DIPG). Ewing Sarcoma, acute myeloid leukemia (AML), ependymoma, or neuroblastoma. Treatment methods include administering the disclosed polypeptides to a subject that may also be treated with radiation. Disclosed herein are systems for treating one or more cancers. The systems may comprise a radiation source, for example a medical fractionated radiation source.

The disclosure provides methods of treating a refractory or relapsed acute myeloid leukemia (AML) in a subject comprising administration of a cell comprising a nucleic acid molecule encoding a chimeric antigen receptor (CAR), wherein the CAR comprises an antibody or antigen-binding fragment thereof that binds IL-1RAP, a transmembrane domain, and an intracellular signaling domain comprising at least a stimulatory domain, wherein prior to administering the cell, the subject is preconditioned with a lymphodepleting chemotherapy (LDC).

There is provided a genetically modified cell wherein at least one gene has been deleted from the cell and the gene is selected from the group consisting of p50, p52, p65, c-Rel, and RelB. Also disclosed are methods of identifying a target for treating acute myeloid leukemia (AML) in a subject, methods of treating acute myeloid leukemia (AML) in a subject in need thereof, comprising inhibiting the activity of an NF-KB pathway. Also provided is an ATP13A2 inhibiting agent for use in therapy or medicine, for use in treating AML, and in the manufacture of a medicament for treating AML.

The invention discloses a novel application of a known eIF5B inhibitor in treating acute myelogenous leukemia (AML). It is found for the first time that the eIF5B inhibitor has high toxicity to various AML cells, can inhibit proliferation of the various AML cells and induce differentiation of the AML cells, has no significant influence on normal hematopoietic stem / progenitor cells, and can be used for developing drugs for treating AML. The invention provides a theoretical basis for research and development of anti-AML drugs, opens up a new application of the eIF5B inhibitor, provides a brand new method for treating AML, and has a wide application prospect in the technical field of AML treatment.

The present disclosure relates to compounds and compositions for inhibiting Bcr-Abl tyrosine kinase, methods for preparing the compounds and compositions, and the use of the compounds and compositions in treating various cancers such as chronic myeloid leukemia (CML).

The invention relates to application of a GSTP1 inhibitor in preparation of a medicine for treating chronic myelogenous leukemia, and belongs to the technical field of biomedicine. According to the application, it is found for the first time that interaction exists between CML core driving proteins BCR-ABL1 and GSTP1, GSTP1-mediated BCR-ABL1 protein glutathione modification can be effectively inhibited through targeted inhibition of the expression level of the GSTP1, the stability of the BCR-ABL1 protein is reduced, CML cell proliferation is inhibited, and CML cell apoptosis is promoted, so that the effect of treating the chronic myeloid leukemia is achieved. Therefore, the GSTP1 can be used as a treatment target, the GSTP1 inhibitor Ezatiostat is used for preparing the medicine for treating the chronic myelogenous leukemia, a theoretical basis and possibility are provided for developing a GSTP1 inhibitor and TKI combined medication scheme in the future, synergistic interaction is expected, and prognosis of a patient is further improved.

Disclosed herein are embodiments of a method for treating a disease or condition in a subject, comprising administering to the subject, a pyrazole compound according to formula I.The compound may be administered as a composition, such as a spray-dried formulation. The disease or condition may be hidradenitis suppurativa, or a lymphoid neoplasm, and may be chronic myeloid leukemia or chronic myelomonocytic leukemia.

The invention discloses a staurosporine glucoside derivative as well as a preparation method and application thereof, and belongs to the field of medicine synthesis. C3-NHCH3 of staurosporine is subjected to glycosylation modification, and the staurosporine glycoside derivative shown in the formula (I) is prepared. The glycoside derivative prepared by the invention has a better inhibition effect on human acute myeloid leukemia cells THP-1, human bladder cancer cells 5637, human colon cancer cells HCT-116, human pancreatic cancer cells PATU8988T and human liver cancer cells HuH-7, and the compound 5 also has an excellent inhibition effect on human gastric cancer cells MKN-45. A candidate compound is provided for development of drugs for bladder cancer, colon cancer, pancreatic cancer, liver cancer, stomach cancer or acute myeloid leukemia.

The present application relates to anti-CD38 antibodies for the treatment of acute myeloid leukemia. The present invention relates to methods of using anti-CD38 antibodies for the treatment of acute myeloid leukemia.

The present invention relates to methods of treating leukemia using Tyrosine Kinase inhibitors. The invention particularly relates to methods of treating CML and ALL using a compound of Formula I or a pharmaceutically acceptable salt thereof. The compound of Formula 1 has been shown to be efficacious safe and tolerable at a dose from 10 mg to 210 mg.

This invention belongs to the field of biomedical technology, specifically relating to a culture reagent composition and method for organoids from hematologic malignancies. The invention first provides a reagent composition for culturing organoids from hematologic malignancies, including acute lymphoblastic leukemia or acute myeloid leukemia; the reagent composition includes a bone marrow microenvironment mimicking matrix reagent and a specific culture medium. Using the reagent composition of this invention, hematologic malignancies can be cultured efficiently with high survival rates. Furthermore, the bone marrow microenvironment mimicking matrix component used in this invention, compared to the commonly used Matrigel matrix in the field, allows for more accurate phenotypic differentiation of hematologic malignancies.

Disclosed in the present invention are a PIM kinase inhibitor as shown in general formula II, a pharmaceutical composition thereof, a preparation method therefor and the use thereof in the preparation of a drug for preventing and / or treating indications related to a PIM signaling pathway. The compound of the present invention is an ideal PIM kinase inhibitor with a high activity, which can be used for treating and / or preventing diseases including autoimmune diseases and tumors, e.g., inflammatory bowel disease, hematologic malignancies such as acute myeloid leukemia, myelofibrosis and chronic lymphocytic leukemia, and solid tumors such as gastric cancer and prostate cancer.