37 results about "Bromodomain" patented technology

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.

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.

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 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 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.

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 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 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.

The present invention relates to a polypeptide comprising a histone code reader domain and uses thereof, in particular to a polypeptide comprising the PHD domain of PHF6 (PHD finger protein 6), optionally DPF3b (double PHD fingers 3b) or BPTF (bromodomain PHD finger transcription factor) or variants thereof, and uses thereof for the prevention or treatment of cancer.

The present invention provides for compounds of formula (I)wherein R1, R2, R3, R4, R6, X1, and X2 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 application discloses an E3 ubiquitin ligase FBXO22-mediated molecular glue degrader and application thereof, and relates to the technical field of medicinal chemistry. Based on the principle of targeted protein degradation, a series of E3 ubiquitin ligase FBXO22-mediated molecular glue degraders are designed and synthesized. The structure of the molecular glue degrader is shown in formula I or formula II: wherein R 1 and R 2 at least one contains alkylamine substitution. The application screens the activity of the compound by high-content screening technology and Western blotting technology, confirms that the molecular glue degrader can induce the degradation of bromodomain-containing protein 4 and other proteins in its family by E3 ubiquitin ligase FBXO22, thereby can hinder the relevant downstream pathway signals, has the activity of inducing cancer cell death and anti-fibrosis, and is expected to provide a new drug research direction for the treatment of bromodomain protein-related cancer and fibrosis diseases.

The invention discloses an E3 ubiquitin ligase FBXO22 mediated molecular glue degradation agent and application thereof, and relates to the technical field of medicinal chemistry. The invention designs and synthesizes a series of E3 ubiquitin ligase FBXO22 mediated molecular glue degradation agents on the basis of a targeted protein degradation principle. The structure of the molecular glue degradation agent is shown as a formula I or a formula II, and at least one of R1 and R2 contains alkylamine substitution. The activity of a compound is screened through a high content screening technology and a protein immunoblotting technology, and it is confirmed that the molecular glue degradation agent can induce degradation of bromodomain protein 4 and other proteins in the family of the bromodomain protein 4 by using E3 ubiquitin ligase FBXO22, so that related downstream channel signals can be hindered; the compound has cancer cell death induction and anti-fibrosis activity, and is expected to provide a new drug research direction for treatment of bromodomain protein related cancers and fibrosis diseases.

Disclosed herein are bifunctional compounds of the formula: (I) A— L— B and pharmaceutically acceptable salts thereof, wherein: A is an inhibitor of a poly (ADP-ribose) polymerase (PARP) protein; L is a linker that resists cleavage in plasma; and B is an inhibitor of a bromodomain and extraterminal (BET) protein. Also disclosed are methods of preparing such compounds, compositions comprising them, and methods of their use to treat cancer.

The diagnostic markers that provide novel diagnostic criteria to blastic plasmacytoid dendritic cell neoplasm (BPDCN) has been searched, and the presence of immunoblastoid cytomorphology, 8q24 rearrangement, and MYC expression were established as novel markers for subtyping BPDCN. It has been further found that the inhibitors which directly or indirectly inhibit the expression, functions, or signaling pathways of MYC, such as BET bromodomain-selective inhibitors or aurora kinase inhibitors, are effective in MYC-positive BPDCN, and HDAC inhibitors or BCL2 family protein inhibitors are effective as therapeutic drugs for BPDCN.

The present invention particularly relates to (i) a combination of a CBP / p300 bromodomain inhibitor and a KRAS inhibitor for treating a patient with cancer, wherein the cancer exhibits carcinogenic alterations in KRAS; (ii) a kit comprising (a) a pharmaceutical formulation containing a CBP / p300 bromodomain inhibitor and (b) a pharmaceutical formulation containing a KRAS inhibitor; and (iii) a pharmaceutical formulation comprising a CBP / p300 bromodomain inhibitor and a KRAS inhibitor.

The present disclosure is directed to solid and salt forms of inhibitors of the CBP / p300 family of bromodomains made up of salts and crystalline forms of Formula (I). 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 that are kinase inhibitors. The compounds have improved properties that lead to specific targeting of kinases without inhibiting the activity of related enzymes, which make them useful for therapeutic intervention in a variety of disorders and disease in which inhibition of the kinase can be clinically useful, e.g., Alzheimer's disease and other neurodegenerative diseases. The compounds can also be used in methods of treating a neurodegenerative disease associated with inflammation, such as Alzheimer's disease, Huntington's disease, Parkinson's disease, epilepsy, stroke, amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA), or a disease or disorder such as deafness, glaucoma, organ failure, or cancers, including, but not limited to, those susceptible to combination therapy with epigenetic targets such as those associated with bromodomain (BRD) proteins, histone deacetylases (HDACs), and the like.

The invention discloses a preparation method and application of a quinazolinone-diketopiperazine heterozygote BRD4 inhibitor, belongs to the technical field of medicines, and particularly relates to the quinazolinone-diketopiperazine heterozygote BRD4 inhibitor shown in a general formula (I), pharmaceutically acceptable salt or stereoisomer thereof, and R1-R8, X, Y, Z or W are defined in the specification. The invention also relates to a preparation method of the compounds, and a pharmaceutical preparation or a pharmaceutical composition containing the compounds. The quinazolinone-diketopiperazine heterozygote BRD4 inhibitor provided by the invention has strong inhibitory activity (IC50 = 0.92 nM) and high selectivity (170323 times) on a second bromo-domain, which is stronger than that of a clinical test drug RVX-208 (17 times), and NO generation inhibitory activity is stronger than that of RVX-208, so that the quinazolinone-diketopiperazine heterozygote BRD4 inhibitor is expected to be applied to preparation of drugs for preventing or / and treating inflammation, and has broad application prospects. The compound can be particularly applied to preparation of drugs for preventing or / and treating acute inflammation (such as septicemia), and has a remarkable medicinal prospect.

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 present disclosure is directed to solid and salt forms of inhibitors of the CBP / p300 family of bromodomains made up of salts and crystalline forms of Formula (I). 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.