1445993-89-4Relevant academic research and scientific papers
METHODS AND COMPOUNDS FOR THE TREATMENT OF GENETIC DISEASE
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, (2021/08/13)
The present disclosure relates to compounds and methods for modulating the expression of dmpk, and treating diseases and conditions in which dmpk plays an active role. The compound can be a transcription modulator molecule having a first terminus, a second terminus, and oligomeric backbone, wherein: a) the first terminus comprises a DNA-binding moiety capable of noncovalently binding to a nucleotide repeat sequence CAG or CTG; b) the second terminus comprises a protein-binding moiety binding to a regulatory molecule that modulates an expression of a gene comprising the nucleotide repeat sequence CAG or CTG; and c) the oligomeric backbone comprising a linker between the first terminus and the second terminus.
BRD4 inhibitor as well as a preparative method and use thereof
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, (2021/05/21)
The compound of formula (I) has a good inhibitory effect on the proliferation of human prostate cancer cells CWR22RV1 and breast cancer cells; and combined use of the compound with an androgen receptor inhibitor HC-1119 significantly enhances the inhibitory effect on prostate cancer cells, and the inhibitory effect increases with increased concentration. The compound of formula (I) can not only be used independently to prepare an antineoplastic agent but can also be used in combination with other agents having antineoplastic effects, such as an androgen receptor inhibitor, or other targeting drugs etc., to prepare an antineoplastic agent having stronger therapeutic effects, especially an agent for treating prostate cancer and breast cancer.
Indole compound as well as preparation method and application thereof
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Paragraph 0053-0055, (2021/09/21)
The invention provides an indole compound which has a structure as shown in a formula I. The invention also provides a preparation method and application of the compound shown in the formula I. The compound as shown in the formula I has excellent inhibitory activity on BRD4 protein and has potential application value in preparation of drugs for treating tumors.
BET INHIBITORS FOR MODULATING DUX4 EXPRESSION IN FSHD
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, (2020/07/14)
The present disclosure provides BET inhibitors of the formula: wherein the variables are defined herein, as well as pharmaceutical compositions thereof. The present disclosure also provides methods of treating a patient comprising administering a bromo- and extra-terminal (BET) domain inhibitor for the treatment of FSHD which modulates DUX4 expression. In some embodiments, the present methods comprise using one or more BET inhibitors as a therapeutic agent for the treatment of FSHD patients including patients who are being treated with one or more palliative treatments such as therapy and/or agents which lead to increased muscle mass.
Antibody Conjugation of a Chimeric BET Degrader Enables in vivo Activity
Pillow, Thomas H.,Adhikari, Pragya,Blake, Robert A.,Chen, Jinhua,Del Rosario, Geoffrey,Deshmukh, Gauri,Figueroa, Isabel,Gascoigne, Karen E.,Kamath, Amrita V.,Kaufman, Susan,Kleinheinz, Tracy,Kozak, Katherine R.,Latifi, Brandon,Leipold, Douglas D.,Sing Li, Chun,Li, Ruina,Mulvihill, Melinda M.,O'Donohue, Aimee,Rowntree, Rebecca K.,Sadowsky, Jack D.,Wai, John,Wang, Xinxin,Wu, Cong,Xu, Zijin,Yao, Hui,Yu, Shang-Fan,Zhang, Donglu,Zang, Richard,Zhang, Hongyan,Zhou, Hao,Zhu, Xiaoyu,Dragovich, Peter S.
, p. 17 - 25 (2019/11/20)
The ability to selectively degrade proteins with bifunctional small molecules has the potential to fundamentally alter therapy in a variety of diseases. However, the relatively large size of these chimeric molecules often results in challenging physico-chemical properties (e. g., low aqueous solubility) and poor pharmacokinetics which may complicate their in vivo applications. We recently discovered an exquisitely potent chimeric BET degrader (GNE-987) which exhibited picomolar cell potencies but also demonstrated low in vivo exposures. In an effort to improve the pharmacokinetic properties of this molecule, we discovered the first degrader-antibody conjugate by attaching GNE-987 to an anti-CLL1 antibody via a novel linker. A single IV dose of the conjugate afforded sustained in vivo exposures that resulted in antigen-specific tumor regressions. Enhancement of a chimeric protein degrader with poor in vivo properties through antibody conjugation thereby expands the utility of directed protein degradation as both a biological tool and a therapeutic possibility.
COMPOUND FUNCTIONING AS BROMODOMAIN PROTEIN INHIBITOR, AND COMPOSITION
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, (2020/11/22)
The invention relates to a bromodomain inhibitor. The invention also provides compositions and formulations comprising such compounds, and methods of using and preparing such compounds.
TERT-BUTYL (S)-2-(4-(PHENYL)-6H-THIENO[3,2-F][1,2,4]TRIAZOLO[4,3-A] [1,4]DIAZEPIN-6-YL) ACETATE DERIVATIVES AND RELATED COMPOUNDS AS BROMODOMAIN BRD4 INHIBITORS FOR TREATING CANCER
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, (2020/05/06)
The present disclosure relates to te rt-butyl (S)-2-(4-(phenyl)-6H-thieno[3,2-f][l,2,4]triazolo[4,3-a] [l,4]diazepin-6-yl) acetate derivatives and related compounds as bromodomain BRD4 inhibitors for treating cancer. Exemplary compounds are e.g. tert-butyl (S)-2-(4-(4-(3-aminoprop-l-yn-l-yl)phenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][l,2,4]triazolo[4,3-a][l,4]diazepin-6-yl)acetate (example 1, compound la), tert-butyl(S,E)-2-(4-(4-(3-aminoprop-l-en-l-yl)phenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][l,2,4]triazolo[4,3-a][l,4]diazepin-6-yl)acetate (example 6, compound 6a) or tert-butyl(S)-2-(4-(4-(3-(hydroxyamino)prop-l-yn-l-yl)phenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][l,2,4]triazolo[4,3-a] [l,4]diazepin-6-yl)acetate (example 8, compound 8a).Results of biological assays, such as e.g. BRD4 BD1 and BD2 binding (table 2), cell proliferation assays (table 6) and inhibition of MYC expression in MV-4-11 cells (table 7) are disclosed.
COMPOUNDS COMPRISING N-METHYL-2-PYRIDONE, AND PHARMACEUTICALLY ACCEPTABLE SALTS
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, (2020/12/30)
The present invention concerns compounds comprising N-methyl-2-pyridone, and pharmaceutically-acceptable salts and compositions of such compounds. Such compounds are useful in anti-inflammatory and anti-cancer therapies. Therefore, the present invention also concerns such compounds for use as medicaments, particularly for the treatment of inflammatory diseases and oncology.
(4-HYDROXYPYRROLIDIN-2-YL)-HETEROCYCLIC COMPOUNDS AND METHODS OF USE THEREOF
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, (2019/05/15)
The present disclosure relates to bifunctional compounds of formula (I), which can be used as modulators of targeted ubiquitination. In particular, the present disclosure is directed to compounds which contain on one end a VHL ligand moiety, which binds to the VHL E3 ubiquitin ligase, and on the other end a moiety that binds a target protein such that degradation of the target protein/polypeptide is effectuated. Also disclosed are VHL ligands of formula (III).
BET protein inhibitor and preparation method and application thereof
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, (2019/07/29)
The invention belongs to the technical field of biological medicine, and particularly relates to a BET protein inhibitor and a preparation method and application thereof. Compared with the prior art,structural improvement is further conducted on the basis
