63 results about "Bromodomain" patented technology

The present invention relates to: a recombinant polypeptide comprising a bromodomain variant; a chimeric antigen receptor comprising the bromodomain variant in an intracellular signaling domain; a gene construct comprising a nucleotide sequence encoding the recombinant polypeptide or the chimeric antigen receptor; a cell or an immune cell, each expressing the recombinant polypeptide or the chimeric antigen receptor; a pharmaceutical composition for the prevention or treatment of cancer, comprising the immune cell; a composition for degrading the recombinant polypeptide or chimeric antigen receptor of the immune cell, the composition comprising a PROTAC compound as an active ingredient; and a kit for the prevention or treatment of cancer, comprising the pharmaceutical composition and the PROTAC compound.

Described herein are methods of for treating and / or preventing Major adverse cardiovascular events (MACE). by administering to a subject in need thereof, a combination of a sodium-glucose transport protein 2 (SGLT2) inhibitor and a compound of Formula I or a stereoisomer, tautomer, pharmaceutically acceptable salt, or hydrate thereof, wherein the variables of Formula I are as defined herein.

The present invention provides: a novel compound inhibiting the activity of bromodomain, a solvate thereof, a hydrate thereof, a prodrug thereof, an isomer thereof, or a pharmaceutically acceptable salt thereof; and a pharmaceutical composition comprising same, and is very useful for preventing and treating diseases and disorders responding to the inhibition of bromodomain-containing proteins.

The present disclosure is directed to inhibitors of the CBP / p300 family of bromodomains. The compounds can be useful in the treatment of disease or disorders associated with the inhibition of the CBP / p300 family of bromodomains. For instance, the disclosure is concerned with compounds and compositions for inhibition of the CBP / p300 family of bromodomains, methods of treating, preventing, or ameliorating diseases or disorders associated with the inhibition of CBP / p300 family of bromodomains, and methods of synthesis of these compounds.

The present disclosure is directed to inhibitors of the CBP / p300 family of bromodomains. The compounds can be useful in the treatment of disease or disorders associated with the inhibition of the CBP / p300 family of bromodomains. For instance, the disclosure is concerned with compounds and compositions for inhibition of the CBP / p300 family of bromodomains, methods of treating diseases or disorders associated with the inhibition of CBP / p300 family of bromodomains (e.g., certain forms of cancer), and methods of synthesis of these compounds.

Provided are compounds having bromodomain inhibitory activity and the use thereof. The compounds have structures shown as formula I. The compounds can selectively inhibit the BD2 bromodomain of the BET family, and can be used as new-generation bromodomain inhibitors for treating BET-related diseases such as cancers and inflammations.

The present invention relates to a polypeptide comprising a histone cipher reader domain and a use thereof, and more particularly, to a polypeptide and a use thereof in the prevention or treatment of cancer, the polypeptide comprising a PHD domain of PHF6 (PHD finger Protein 6), optionally comprising DPF3b (Double PHD finger 3b) or BPTF (Bromodomain PHD finger transcription factor), or a mutant thereof, and to a use thereof in the prevention or treatment of cancer, and more particularly, to a polypeptide comprising a PHD domain of PHF6 (PHD finger Protein 6), optionally comprising DPF3b (Double PHD finger 3b) or BPTF (Bromodomain PHD finger transcription factor), or a mutant thereof.

Crystalline and salt forms of a bromodomain protein inhibitor represented by formula (I), methods for producing the same, and use of the crystal and salt forms in the manufacture of a medicament for treating a BET protein-mediated disease. [Formula 1] TIFF2023510610000055.tif33133

The invention relates to a compound capable of being used as a BET / p300 bromodomain double-target inhibitor or a derivative thereof as well as a preparation method and application of the compound. The compound has a structure as shown in a formula I, wherein substituent groups R1 to R4 in the formula # imgabs0 are defined in the specification. The invention also relates to a pharmaceutical composition containing the compound or the derivative thereof, application of the compound or the derivative thereof as a BET / p300 bromodomain double-target inhibitor, and a preparation method of the compound or the derivative thereof. The compound or the derivative thereof can significantly inhibit the activity of BET / p300 bromodomain, has a significant anti-proliferation effect on cancer cells and multiple myeloma cells, and also has good metabolic stability, safety and drug-likeness, so that the compound or the derivative thereof has a wide application prospect.

The present disclosure concerns a compound of formula (I) and / or a tagged compound of formula (IA), each of which are capable of binding to a complementary hole-modified mutant bromodomain, also presented herein. The disclosure also concerns the use of the compounds in various applications, a method of covalently binding a target biomolecule with a compound or tagged compound, and a kit comprising: a compound or tagged compound, and a construct comprising a nucleic acid encoding a complementary hole-modified mutant bromodomain.

The present invention discloses an application of a bromodomain protein 4 active compound based on a water network strategy. The bromodomain protein 4 active compound can be used to prepare a drug that inhibits the activity of bromodomain protein 4, and can be used to prepare a pharmaceutically acceptable salt. In addition, the bromodomain protein 4 active compound and the pharmaceutically acceptable salt prepared therefrom can also be used to prepare a bromodomain protein 4 inhibitor and the pharmaceutically acceptable salt prepared therefrom, as well as a pharmaceutical composition for preparing a prostate cancer cell proliferation inhibitor, an anti-prostate tumor drug, and a pharmaceutical composition for treating bromodomain protein 4-related diseases. The bromodomain protein 4 inhibitor prepared based on the bromodomain protein 4 active compound having obvious inhibitory activity of the present invention is applied to the treatment of diseases related to bromodomain protein 4, has high reliability, is easy to promote and popularize, and utilizes the potential advantages of the bromodomain protein 4 active compound as a drug or pharmaceutical composition, opening up a new approach for the treatment of related diseases.

Provided herein are methods and compositions for treating cancer by administering an in-situ cancer vaccine, such as comprising tumor directed radiation therapy and a Bromodomain and Extra-Terminal motif (BET) inhibitor.

The present invention provides for compounds of formula (I)wherein R1, Y, X1, X2, R2, R3, R4, R5, R6, and m have any of the values defined in the specification, and pharmaceutically acceptable salts thereof, that are useful as agents in the treatment of diseases and conditions, including inflammatory diseases, cancer, and AIDS. Also provided are pharmaceutical compositions comprising compounds of formula (I).

The present invention concerns a method of degrading target proteins, by forming fusion proteins which comprise hole-modified mutant BET bromodomains conjugated to the target protein and using a degrader compound to initiate protein degradation.

The invention provides application of a super enhancer inhibitor JQ-1 in preparation of a medicine for treating wound healing disorder related diseases. Relates to the technical field of biomedicine, the promotion effect of the super enhancer inhibitor JQ-1 in wound healing and repairing is disclosed for the first time, the super enhancer inhibitor JQ-1 is competitively combined with BET protein bromodomain, combination of the super enhancer inhibitor JQ-1 and acetylated histone is blocked, and super enhancer driven gene transcription is inhibited. Skin regeneration can be obviously accelerated, the wound healing time is shortened, and the healing degree is improved. Aiming at the pain point that the existing wound healing therapy is limited in effect, the invention provides a brand-new molecular targeted therapy scheme for people, such as diabetic patients and old people, which are easy to cause abnormal wound healing, can effectively reduce serious sequelae, such as amputation, and provides a scientific basis and a key direction for developing a novel medicine for promoting wound healing; the technical blank in the related treatment field is filled up, and important clinical application value and research and development prospects are achieved.

The present invention relates to bifunctional compounds, which find utility as modulators of targeted ubiquitination, especially inhibitors of a variety of polypeptides and other proteins which are degraded and / or otherwise inhibited by bifunctional compounds according to the present invention. In particular, the present invention is directed to compounds, which contain on one end a VHL ligand which binds to the ubiquitin ligase and on the other end a moiety which binds a target protein such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of that protein. The present invention exhibits a broad range of pharmacological activities associated with compounds according to the present invention, consistent with the degradation / inhibition of targeted polypeptides.

Provided in the present invention is an indolizine compound having a structure as represented by formula I, formula II, or formula III. The indolizine compound provided in the present invention can effectively bind to a BRD7 / BRD9 bromodomain, and has a good effect. Moreover, the indolizine compound provided in the present invention has a stable structure and a simpler synthesis method.

Described herein are methods for treating and / or preventing a kidney disease or an associated disorder as measured by an increase in estimated glomerular filtration rate (eGFR) by administering to a subject in need thereof, a combination of a sodium-glucose transport protein 2 (SGLT2) inhibitor and a compound of Formula I or a stereoisomer, tautomer, pharmaceutically acceptable salt, or hydrate thereof, wherein the variables of Formula I are as defined herein.

In aspects, the present disclosure provides a method of treating or preventing a uterine fibroid in a female mammal, the method comprising, consisting essentially of, or consisting of administering to the female mammal an effective amount of an inhibitor of bromodomain (BRD) protein.

Provided herein are processes which are useful for the preparation of small molecule bromodomain inhibitors.

The invention relates to compounds according to the general formula (1), and to the use thereof for production of a medicament, especially for treatment of a disorder associated with bromodomains, such as cancer.

The invention provides a compound of formula I: or a salt thereof, wherein R1, R2, A, B, D, E, F, G, and X have any of the values described in the specification, as well as compositions comprising a compound of formula I. The compounds are useful as bromodomain inhibitors.

To provide solid crystalline forms of a compound that modulates or inhibits the activity of BET bromodomain-containing proteins.SOLUTION: Provided is a form of Compound I which: (a) when measured on a diffractometer using a Cu-Kα radiation source, has three or more characteristic XRPD peaks at 2θ of 7.2, 10.3, 11.2, 12.0, 13.8, 13.9, 15.2, 15.6, 16.5, 17.3, 20.7, 20.9, 21.6, and 22.5°, wherein each peak is at ±0.2°θ; or (b) when measured on a diffractometer using a Cu-Kα radiation source, has six or more characteristic XRPD peaks at 2θ of 7.2, 10.3, 11.2, 12.0, 13.8, 13.9, 15.2, 15.6, 16.5, 17.3, 20.7, 20.9, 21.6, and 22.5°, wherein each peak is at ±0.2°θ.SELECTED DRAWING: None

The invention relates to solid crystalline forms of Compound (I), such as e.g., Form VII, including pharmaceutical compositions thereof and processes for preparing crystalline Compound (I), Form VII. Compound (I) modulates or inhibits the activity of BET bromodomain-containing proteins, and is useful in the treatment of diseases such as cancer, inflammatory and cardiovascular diseases.

The present invention is inter alia concerned with (i) a combination of a CBP / p300 bromodomain inhibitor and a KRAS inhibitor for use in the treatment of a patient suffering from cancer, wherein the cancer exhibits an oncogenic alteration in the KRAS; (ii) a kit comprising (a) a pharmaceutical dosage form comprising a CBP / p300 bromodomain inhibitor and (b) a pharmaceutical dosage form comprising a KRAS inhibitor, and (iii) a pharmaceutical dosage form comprising a CBP / p300 bromodomain inhibitor and a KRAS inhibitor.

The present disclosure relates to compounds, compositions, and methods for treating diseases or conditions mediated by aberrant Bromodomain PHD Finger Transcription Factor (BPTF) activity.

The invention relates to compounds and methods of treating diseases including but not limited to, cancer, non-cancer proliferative disease, sepsis, autoimmune disease, viral infection, atherosclerosis, Type 1 or 2 diabetes, obesity, inflammatory disease, or Myc-dependent disorder including by modulating biological processes by the inhibition of cell cycle checkpoint targets CDKs, and / or PI3 kinase, and / or bromodomain protein binding to substrates, comprising the administration of a compound(s) of Formula 1-V1 (or pharmaceutically acceptable salts thereof) as defined herein.

The disclosure relates to inhibitors of bromodomain and extra-terminal domain (BET) proteins and use thereof for the treatment of disease.

The method of generating multipotent stem cells is a method for producing and / or expanding multipotent stem cells by delivering at least one reprogramming protein into somatic cells. The at least one reprogramming protein includes a Master Regulator (MR) protein, which may be BAZ2B, ZBTB20, ZMAT1, CNOT8, KLF12, DMTF1, HBP1, or FLI1. The bromodomain protein BAZ2B, in particular, was identified by first generating bi-species heterokaryons by fusing Tcf7l1− / − murine embryonic stem cells (ESCs) with human B-cell lymphocytes. Reprogramming of the B-cell nuclei to a multipotent state was tracked by human mRNA transcript profiling at multiple timepoints. Interrogation of a human B-cell regulatory network with gene expression signatures collected from such reprogramming time series identified eight candidate Master Regulator proteins, which were validated in human cord blood-derived hematopoietic progenitor and lineage-committed cells.