194 results about "Proliferative disease" patented technology

The present disclosure provides compounds of Formula (I), (II), and (III). The provided compounds are able to bind protein kinases (e.g., SIK) and may be useful in modulating (e.g., inhibiting) the activity of a protein kinase (e.g., SIK, (e.g., SIK1, SIK2, or SIK3)) in a subject or cell. The provided compounds may be useful in treating or preventing a disease (e.g., proliferative disease, musculoskeletal disease, genetic disease, hematological disease, neurological disease, painful condition, psychiatric disorder, or metabolic disorder) in a subject in need thereof. Also provided are pharmaceutical compositions, kits, methods, and uses that include or involve a compound described herein.

Disclosed are compounds of Formula (I) or a salt thereof, wherein Ring A is a carbon-linked ring; and Ring A, R1, and n are defined herein. Also disclosed are methods of using such compounds to inhibit Helios protein, and pharmaceutical compositions comprising such compounds. These compounds are useful in the treatment of viral infections and proliferative disorders, such as cancer.

The present disclosure is related to dual mechanism of action payload antibody drug conjugates comprising at least two payload residues, pharmaceutical compositions thereof, and the use of the antibody drug conjugates and compositions thereof for the treatment of diseases and disorders, including proliferative diseases.

The present disclosure is related to antibody conjugates, including antibody drug conjugates, comprising multiple payloads at high payload to antibody ratios, pharmaceutical compositions thereof, and the use of the antibody conjugates and compositions thereof for the treatment of diseases and disorders, including proliferative diseases.

This invention provides compounds for the treatment, prevention, or suppression of various pathological conditions (such as proliferative disorders like cancer, β-globin disorders, fibrosis, pain, neurodegenerative diseases, Prader-Willi syndrome, malaria, viral infections, myopathy, and autism) by inhibiting G9a. [Solution] The following general formula (I) TIFF2026062914000401.tif2449 A compound represented by or a pharmacoposly acceptable salt thereof is provided.

Disclosed are new anti-HER2 ADCs conjugated to camptothecin derivatives as toxins for therapeutic use. The antitumor effects of the ADCs of Formula (PL-A) (e.g., compounds MB-2a and MB-3a (trastuzumab meditecan)) render these compounds useful for treating cell proliferative diseases such as cancers.

The present invention provides novel compounds of Formula (I) and pharmaceutically acceptable salts, solvates, hydrates, tautomers, stereoisomers, isotopically labeled derivatives, and compositions thereof. Also provided are methods and kits involving the compounds or compositions for treating or preventing proliferative diseases in a subject, wherein the proliferative diseases include cancer, benign neoplasm, angiogenesis, inflammatory disease, autoinflammatory disease, and autoimmune disease, and the cancer includes leukemia, melanoma, multiple myeloma. Treatment of a subject having a proliferative disease with the compounds or compositions of the present invention can inhibit abnormal activity of cyclin-dependent kinase 7, thus inducing apoptosis and / or inhibiting transcription in the subject.

The invention relates to bispecific antigen binding proteins (ABP), such as bispecific antibodies, that bind with a first antigen binding site to both leukocyte immunoglobulin-like receptor subfamily B1 (LILRB1) and LILRB2 while not binding to, or binding with significantly less affinity to, leukocyte immunoglobulin-like receptor subfamily A (LILRA). The bispecific ABP of the invention bind with a second antigen binding site to immune checkpoint (molecules) such as PD-1 or PD-L1. The bispecific ABP of the invention can also inhibit the interaction between LILRB1 and / or LILRB2 and a natural ligand of ULRB receptors (e.g. interacting proteins, such as HLA-G) on immune cells and the inhibition of such interaction can reduce immune cell suppression and thereby support anti-infection and anti-tumour immune responses in a subject suffering from such diseases. Bispecific molecules combining LILRB1 / 2 antagonism with inhibition of immune checkpoints, such as the inhibition of the PD-1 / PD-L1 axis, is specifically useful in the treatment of proliferative disorders. Also provided are methods of reducing the immune suppression of cells involved with a cell-mediated immune response, and / or methods for treating infective- and / or proliferative diseases, using an LILRB1 and / or LILRB2 antigen binding protein such as an antibody binding to both LILRB1 and / or LILRB2, as well as certain related aspects including detection, diagnostic and screening methods.

Novel, antimitotic heteroaryl amides and pharmaceutically acceptable salts of Formula I where Ar, R5, R6, R8, R9, R11, X1, and X2 are as defined herein, as compounds for treatment and prevention of cancer and proliferative diseases and disorders.

The present disclosure provides a group of aromatic (e.g., pyridinyl, pyrimidinyl, pyrazinyl, or phenyl) diamidine analogs and pharmaceutically acceptable salts that are useful for treating a proliferative disease. The proliferative disease may include solid cancer or blood cancer. Compositions, methods of synthesizing the same and methods for treating various cancer using the analogs are disclosed herein. The present disclosure also provides pharmaceutical formulations comprising at least one of the compounds with a pharmaceutically acceptable carrier, diluent or excipient therefor.

Provided herein are methods, assays and kits for detecting methylated genomic DNA and one or more protein biomarkers in one or more biological samples. In some aspects, the disclosure provides methods, assays and kits for detecting or prognosing a proliferative disease, such as colorectal cancer, in a subject based on the presence of methylated genomic DNA and one or more protein biomarkers in one or more biological samples.

The present invention relates to dual payload antibody drug conjugates comprising at least one topoisomerase inhibitor and at least one DNA damage response (DDR) inhibitor, pharmaceutical compositions thereof, and uses of the antibody drug conjugates and compositions thereof in the treatment of diseases and conditions, including proliferative diseases.

Provided herein are heteroaryl compounds, pharmaceutical compositions, and their use in the treatment of a disease or condition, such as a proliferative disorder, inflammatory disorder, autoimmune disorder, or metabolic disorder. In some embodiments, the heteroaryl compounds are represented by Formula I:or a pharmaceutically acceptable salt thereof, wherein values for the variables (e.g., A1, A2, A3, A4, R1A) are as described herein.

The present disclosure provides compounds of Formula (I), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, and prodrugs thereof. The provided compounds may be kinase (e.g., Janus kinase (JAK), e.g., Janus kinase 2 (JAK2)) inhibitors. Also provided are pharmaceutical compositions and kits including the provided compounds. Further provided are methods of using the provided compounds, pharmaceutical compositions, and kits (e.g., for treating a disease (e.g., proliferative disease) in a subject in need thereof).

This invention relates to benzo[a]-5-membered heterocyclic derivatives and their applications. Specifically, this invention discloses compounds with the structures shown in formula (I) or formula (II), wherein the definitions of each group and substituent are as described in the specification. This invention also discloses the use of said compounds in the treatment or prevention of PARG activity-related diseases, particularly proliferative diseases (such as cancer).

The present disclosure relates to antibody-drug conjugates, wherein the drug is a pyrazolo[1,5-a][1,3,5]triazine derivative or a pyrazolo[1,5-a]pyrimidine derivative. In particular, the drug may be a 2-substituted 8-halogeno-N4-(4-(pyridine-2-yl)benzyl)pyrazolo[1,5-a][1,3,5]triazine-2,4-diamine. Such antibody-drug conjugates are particularly useful in treating proliferative diseases, including cancer.

This disclosure relates to cyclic D-peptides, their derivatives, compositions, and combinations. Specifically, cyclic peptides, their compositions, and derivatives can be made without increasing bilirubin levels. This disclosure also provides the use of cyclic peptides, their derivatives, compositions, and combinations for the treatment and / or prevention of proliferative disorders.

The application discloses a pyridopyrimidine compound containing a morpholine structure and a preparation method and application thereof, and belongs to the technical field of medicines. The pyridopyrimidine compound containing the morpholine structure has a strong ability of inhibiting PI3K alpha kinase, and thus can be used as an active ingredient for preparing a therapeutic drug for diseases caused by abnormal activation of PI3K alpha kinase, and shows potential application value in preparation of a drug for treating and / or preventing proliferative diseases and cancers. The application provides important technical support for development of an anticancer drug with high efficiency and better selectivity.

Providing novel compounds for use in the treatment or prevention of cancer and other proliferative conditions SOLUTION: The present invention relates to novel compounds for use, for example, in the treatment or prevention of cancers and other proliferation conditions characterized by cells expressing cytochrome P4501B1 (CYP1B1) and allelic variants thereof. The invention also provides pharmaceutical compositions comprising one or more such compounds for use in medical therapy, for example in the treatment or prophylaxis of cancer or other proliferative conditions, as well as methods of treating cancer or other conditions in a human or non-human animal patient. The present invention also provides methods of identifying novel compounds for use in the treatment or prevention of cancers and other prohferative conditions characterized by cells that express, for example, CYP1B1 and allelic variants thereof. The invention also provides a method for determining the effectiveness of a compound of the invention in treating cancer.SELECTED DRAWING: Figure 1

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.

The present disclosure relates to methods of treating diseases such as neurological, muscular and proliferative diseases using a combination of metformin and rapamycin.

Novel bispecific heterodimeric immunoglobulins that target both a component of the human CD47 antigen and human CD38 antigen are provided and in particular those comprising an anti-CD38 heavy chain variable region and a light chain variable region and an anti-CD47 heavy chain variable region and a light chain variable region. The present invention also relates to the use of this 5 novel class of bispecific heterodimeric immunoglobulins to treat autoimmune and proliferative diseases and in particular cancers such as hematologic malignancies and solid tumors.

The present disclosure provides variants of interleukin-2 and uses thereof. The present disclosure specifically provides a variant protein of interleukin-2 (IL-2) or a fragment thereof, the variant protein and the fragment thereof having amino acid substitutions at the 42nd and 81st positions relative to the amino acid sequence of the wild-type IL-2 as shown in SEQ ID NO: 1. The invention further provides a derivative and a conjugate containing the variant protein or the fragment thereof, a coding nucleic acid molecule, an expression vector and a host cell of the variant protein or the fragment thereof or the derivative thereof, and application of the variant protein or the fragment thereof or the derivative thereof in drugs for treating or preventing proliferative diseases or immune system diseases.

Provided herein are bifunctional compounds with a moiety or domain that is a binder of the ubiquitin receptor RPN13 and another moiety or domain that is a binder of a target protein DOT1L to induce degradation of DOT1L. Also provided are pharmaceutical compositions comprising the bifunctional compounds, and methods of treating and / or preventing diseases (e.g., proliferative diseases, such as cancers). Provided also are methods of inducing the degradation of DOT1L by administering a bifunctional compound or composition described herein, wherein one domain of the bifunctional compound is a binder of the ubiquitin receptor RPN13 and another domain of the compound is a binder of the target protein DOT1L in a subject.

The disclosure is in the field of immunology and oncology, especially for treating, preventing, or inhibiting proliferative diseases, particularly cancer, infectious diseases and disorders associated with dysfunction of TNF cytokines. The disclosure relates to a novel SPD-TNFSF fusion protein including a TNF-superfamily (TNFSF) ligand, or receptor binding domain thereof, fused to a coiled-coil domain of surfactant protein-D (SPD). Also provided a trimeric or multimeric fusion protein including a plurality of SPD-TNFSF fusion proteins. The disclosure also provides an expression vector as mRNA, plasmid or virus including an isolated nucleotide sequence encoding the SPD-TNFSF fusion protein and a cell or a pharmaceutical composition including thereof.

The present invention provides synthetic polypeptides comprising an annexin V protein, or a functional portion or fragment or variant thereof, conjugated to a tumor antigen, or a functional portion or fragment or variant thereof. The invention further provides methods for making said synthetic polypeptides and their use in the treatment of proliferative diseases such as cancer and tumors originating therefrom.

The present invention relates to MOFs for use in imaging and as radiolabeled tracers. More particularly, the invention provides a particle comprising a MOF, optionally at least one targeting moiety and at least one short-lived radionuclide; a composition comprising said particle; said particle or composition for use as an imaging agent; said particle or composition for use in a method for the diagnosis of a proliferative disease; said particle or composition for use in a method for the diagnosis of a chronic inflammatory disease; and a kit comprising a particle comprising a MOF, an optional targeting moiety, and a short-lived radionuclide cation.

Disclosed herein are topoisomerase I compounds represented by Formula I, or a pharmaceutically acceptable salt thereof, and methods of treating proliferative disorders in a subject, comprising administering a compound disclosed herein: