268 results about "Proliferative disease" patented technology

The present application discloses substituted polycyclic heterocycles compound of Formula (I), pharmaceutically acceptable salt and / or solvate and pharmaceutical compositions thereof useful in the treatment of proliferative disease or condition characterized by a dysregulation of the RAS-ERK pathway such as neoplasm disease or disorder, inflammatory disease or immune system disorder.

The present disclosure is related to dual payload immunostimulatory antibody drug conjugates comprising at least STING agonist and at least one cytotoxic agent, pharmaceutical compositions thereof, and the use of the dual payload immunostimulatory antibody drug conjugates and compositions thereof for the treatment of diseases and disorders, including proliferative diseases.

The present invention relates to MOFs for use in imaging and as radiolabeled tracers. More specifically, the present invention provides particles comprising MOFs, optionally at least one targeting moiety, and at least one short-lived radionuclide; compositions comprising the particles; the particles or compositions for use as imaging agents; the particles or compositions for use in methods for diagnosing proliferative diseases; the particles or compositions for use in methods for diagnosing chronic inflammatory diseases; and kits comprising particles comprising MOFs, optionally a targeting moiety, and a short-lived radionuclide cation.

The present disclosure provides a novel bifunctional compound that degrades EGFR, pharmaceutical compositions containing the compound, methods of preparation, and uses of the compounds of the disclosure to treat cell proliferative diseases, such as cancer.

The present invention is directed to the tartrate salt of a FAK inhibitor defined by formula (I) below, and the use of that inhibitor for treating a proliferative disease.

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.

The invention is based on the surprising finding that SIK3 is associated with resistance against anti-tumour immune responses. In particular, the invention provides methods for treating proliferative diseases using inhibitors of SIK3, especially nucleic acid or small molecule inhibitors of SIK3. Also provided are methods of sensitising cells involved with a proliferative disorder against the cytotoxic effect of certain pro-inflammatory signalling pathways, and / or to kill such cells and / or methods for treating proliferative diseases, using a SIK3 inhibitor together with ligands or agonists of such signalling pathways. Other methods provided by the invention include those involving SIK3 inhibitors to enhance or overcome certain side effects associated with treatments that utilise such signalling pathways, as well as diagnostic, prognostic and monitoring methods and kits based on the detection of SIK3 in a sample obtained from a subject, and screening methods useful for identifying or characterising inhibitors of SIK3.

This document provides bifunctional compounds, one part of which (e.g., lenalidomide, thalidomide) is a binder of an E3 ubiquitin ligase (e.g., Cereblon) and the other part of which is a binder of a target protein (e.g., a kinase (e.g., CDK (e.g., CDK9 and / or CDK12))) to induce the degradation of the target protein CDK9 and / or CDK12. Pharmaceutical compositions comprising bifunctional compounds are also provided, as well as methods for treating and / or preventing diseases (e.g., proliferative diseases such as cancers (e.g., ovarian cancer, breast cancer, or prostate cancer)). Methods for inducing the degradation of target proteins (e.g., kinases (e.g., CDK (e.g., CDK9 and / or CDK12))) and methods for inducing apoptosis in biological samples or subjects by administering the bifunctional compounds or compositions described herein are also provided.

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.

Disclosed are compounds of Formula (1): Also disclosed are methods of using such compounds to decrease the levels of Ikaros protein, Helios protein, Aiolos protein, and Eos 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 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.

Disclosed herein are compounds (e.g, compounds of Formula (I), and pharmaceutically acceptable salts, hydrates, solvates, polymorphs, co-crystals, tautomers, isotopically labeled compounds, and prodrugs thereof), and pharmaceutical compositions, kits, methods, and uses thereof. The compounds disclosed herein are inhibitors of TOX protein and are useful for treating diseases (e.g., immune diseases, proliferative diseases, and viral infections).

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.

The invention relates to the technical field of medicines, and discloses camphorsulfonate, a crystal form, a composition and a preparation method and application thereof, and the camphorsulfonate is AXL kinase inhibition camphorsulfonate. The crystal form of the camphorsulfonate is substantially pure. The basically pure AXL kinase inhibition camphorsulfonate crystal form disclosed by the invention has good performance and high bioavailability; therefore, the compound can be used for preparing medicines for treating and / or preventing proliferative diseases, autoimmune diseases, allergic diseases, inflammatory diseases, transplant rejection, cancers, virus infectious diseases, heart failure, cardiovascular diseases or other diseases of mammals.

A tricyclic heterocyclic compound, its preparation, and its applications are disclosed. Specifically, a tricyclic heterocyclic compound as shown in Formula IA or a pharmaceutically acceptable salt thereof is provided. This tricyclic heterocyclic compound exhibits good inhibitory activity against poly(ADP-ribose) polymerase and can significantly inhibit the growth of NCI-H1373 human lung adenocarcinoma cells. It can be used as a drug for the treatment and / or prevention of abnormal proliferative diseases or other diseases related to the targets that this series of compounds targets; for example, cancer.

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 invention relates to the technical field of medicines, and discloses a salt, a crystal form and a composition of an AXL kinase inhibitor as well as a preparation method and application of the salt, the crystal form and the composition of the AXL kinase inhibitor, and the salt is hydrochloride, sulfate, phosphate, mesylate, benzene sulfonate, p-toluenesulfonate, camphorsulfonate, maleate and oxalate. The crystalline form of the AXL kinase inhibitor salt is substantially pure. The basically pure AXL kinase inhibitor crystal form disclosed by the invention has good performance and high bioavailability; therefore, the compound can be used for preparing medicines for treating and / or preventing proliferative diseases, autoimmune diseases, allergic diseases, inflammatory diseases, transplant rejection, cancers, virus infectious diseases, heart failure, cardiovascular diseases or other diseases of mammals.

A compound represented by formula (I) serving as a KIF18A inhibitor, a pharmaceutical composition containing the compound represented by formula (I) or a pharmaceutically acceptable salt thereof, and a use of the compound represented by formula (I) and the pharmaceutical composition in the treatment of cell proliferative diseases, for example, cancers.

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.