91 results about "Myeloid leukemia" patented technology

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.

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 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.

The invention discloses application of an LPIN1 inhibitor in preparation of drugs for treating FLT3-ITD mutant acute myelogenous leukemia, reducing tumor load of a patient with the FLT3-ITD mutant acute myelogenous leukemia, improving the survival rate of the patient with the FLT3-ITD mutant acute myelogenous leukemia and / or reducing the proliferation activity of primary cells of the patient with the FLT3-ITD mutant acute myelogenous leukemia. The LPIN1 inhibitor for inhibiting lipid metabolism related enzyme LPIN1 can significantly induce apoptosis of FLT3-ITD mutant AML cells, has limited influence on non-mutant AML cells, and has mutation specificity. More importantly, the LPIN1 inhibitor (such as propranolol) and the FLT3 inhibitor (such as quinatinib) are combined for use, so that a synergistic anti-leukemia effect can be generated, and a remarkable anti-tumor effect is shown in vitro and in a mouse transplantation tumor model, so that the LPIN1 inhibitor and the FLT3 inhibitor have a good application prospect.

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

This invention relates to a method for constructing a prognostic assessment model for acute myeloid leukemia (AML) with NPM1 mutations. The method includes the following steps: (1) collecting and detecting gene mutation data required for the prognostic assessment system of AML patients with NPM1 mutations, including the mutation status of FLT3-ITD, IDH1, and SRSF2 genes; (2) assigning values ​​according to the mutation status of FLT3-ITD, IDH1, and SRSF2; (3) substituting the values ​​assigned in step (2) into the formula: mNPM1 AML risk score = 1.077 × FLT3-ITD - 0.800 × IDH1 + 1.512 × SRSF2, and performing grouped and parallel prognostic assessments on the calculated values. This invention provides a prognostic assessment model for AML with NPM1 mutations, providing important guidance for the treatment of such patients and having good clinical application value.

The present invention provides a stilbene derivative of guaiazulene, which belongs to the technical field of medicinal chemistry. The present invention combines guaiazulene with a stilbene skeleton for pharmacophore combination to synthesize stilbene derivatives of guaiazulene. This structure contains guaiazulene functional units and stilbene skeleton functional units, which can give such compounds a wide range of anti-tumor and anti-influenza virus activities, laying the foundation for the development of stilbene derivatives of guaiazulene as anti-tumor and anti-influenza virus candidate drugs. The results of the examples show that the stilbene derivatives of guaiazulene provided by the present invention have certain inhibitory activity on human chronic myeloid leukemia cells K562, human breast cancer cells MDA-MB-231, and human pancreatic cancer cells ASPC-1; the stilbene derivatives of guaiazulene provided by the present invention have certain inhibitory activity on H1N1 virus, which is the first time that a compound with antiviral activity has been found from guaiazulene derivatives, broadening the direction of antiviral drug development.

The present disclosure relates to RNAi agents useful in methods of treating KRAS-related diseases such as a proliferative disease, including without limitation a solid or liquid cancer, adenocarcinoma, colorectal cancer, advanced and / or metastatic colorectal cancer, colon cancer, lung, non-small cell lung cancer and lung adenocarcinoma, acute myelogenous lung, bladder, brain, breast, cervical, endometrial, gastric, head and neck, kidney, leukemia, myelodysplastic syndrome, myeloid leukemia, liver, melanoma, ovarian, pancreatic, prostate, testicular, thyroid cancers, and cardio-facio-cutaneous (CFC) syndrome and Noonan syndrome, and similar and related diseases, using a therapeutically effective amount of a RNAi agent to KRAS.

This invention is in the field of medicinal chemistry. In particular, the invention relates to a new class of carbothioamide (and structurally related) small-molecule compounds which function as inhibitors of SIRT5, and their use as therapeutics for the treatment of diseases associated with posttranslational modification functions (e.g., diseases associated with SIRT5 activity) (e.g., cancer (e.g., melanoma, non-small cell lung cancer (NSCLC), hepatocellular carcinoma (HCC), ovarian cancer, colorectal cancer (CRC), acute myeloid leukemia (AML), Ewing's sarcoma, brain cancer, pancreatic cancer, renal cancer, breast cancer, prostate cancer, lung cancer, leukemia and lymphoma), diabetes, autoimmune diseases, inflammatory diseases, fibrotic diseases, cardiovascular diseases, and neurodegenerative diseases).

This invention provides a method for preparing a non-natural humanized chimeric anti-human CD45RA antigen receptor, which specifically binds to the human CD45RA antigen by expressing CAR protein on T cells. Based on a humanized 3A4 antibody, this invention constructs a lentiviral expression vector pLenti / Hu3A4-4-1BB-3ζ. Compared with murine CAR, the humanized CAR significantly reduces immunogenicity, noticeably decreases the production of anti-scFv antibodies, and avoids the HAMA reaction. Research results show that Hu3A4CAR-T cells can specifically bind to the CD45RA-highly expressing myeloid leukemia cell line KG1a. Hu3A4CAR-T cells can target and kill 3A4-positive cell lines and leukemia cells, alleviate the human anti-mouse antibody response, and significantly reduce the production of anti-scFv antibodies, thereby ensuring the CAR's killing activity.

The invention belongs to the technical field of biological medicines, and particularly relates to a culture reagent composition and a culture method for a malignant tumor organ of a blood system. The invention firstly provides a reagent composition for culturing a hematological malignant tumor organoid, wherein the hematological malignant tumor comprises acute lymphoblastic leukemia or acute myeloid leukemia; the reagent composition comprises a bone marrow microenvironment simulation matrix reagent and a specific culture medium. By adopting the reagent composition provided by the invention, the hematoma organs can be efficiently cultured, and the survival rate is high. And compared with Matrigel matrigel commonly used in the field, the bone marrow microenvironment simulation matrix component adopted by the invention enables phenotypic differentiation of hematoma organs to be more accurate.

The invention relates to the technical field of compounds, in particular to VHL derivatives and application thereof in preparation of SMARCA2 degradation agents. Specifically, the invention discloses a compound as shown in a chemical structural formula I, a tautomer, an enantiomer, a diastereoisomer and pharmaceutically acceptable salts, solvates or hydrates thereof. The compound or a pharmaceutical composition containing the compound can be used for preparing a PROTACS degradation agent aiming at an SMARCA2 target spot, and particularly preparing medicines for treating acute myeloid leukemia, myelodysplastic syndrome, uveal melanoma and the like. # imgabs0 #

The present disclosure encompasses, among other things, methods and compositions for use in the treatment of acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), or myelodysplastic disorder (MDS) in subjects that received HCT. The present disclosure relates, at least in part, to T cells engineered to express particular T Cell Receptors (TCRs) and their use in the treatment of acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), or myelodysplastic disorder (MDS) in subjects that received HCT,

The invention relates to the technical field of biomedicine, in particular to a diagnostic kit based on acute leukemia prognosis and drug sensitivity prediction, which comprises a prediction module I and a prediction module II. The prediction module I is used for predicting the clinical survival rate of a patient and takes one or more of 32 molecules such as CCND3, FERMT3 and PLD4 as prognostic markers; the prediction module II is used for predicting the sensitivity of the body to drugs, and one or more molecules of BMP8B, IGF1R, OTULINL, SLC22A15, CERS1 and PDE4A are used as drug sensitivity markers. By constructing a dual prediction model, the limitation of prediction efficiency of a single biomarker is broken through, functional coupling of survival prognosis and multi-drug sensitivity prediction is realized, and a clinically convertible integrated tool is provided for accurate treatment of AML (acute myeloid leukemia).

The invention provides a therapeutic response model for acute myelogenous leukemia (AML) accompanied with myelodysplastic syndrome related genetic abnormality (MRGA) and application thereof, a survival risk scoring model and application thereof, and the survival risk scoring model is constructed based on the lifetime, cytogenetics abnormality, gene mutation and clinical factors of a patient. Patients are divided into a low-risk group, a medium-risk group and a high-risk group through the model, the AUC value of the patients reaches 0.789-0.831 in the period of 1-3 years, and the clinical practicability of the model in the aspect of making AML treatment decisions based on myeloid associated dysplasia (MRGA) is proved through remarkable survival differences among different risk groups. In addition, a combined scoring system for the treatment response and lifetime of the MRGA AML patient is further developed, and a new technical support is provided for clinical decision-making of the MRGA AML.

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