13 results about "HDAC inhibitor" patented technology

This invention belongs to the field of pharmaceutical preparation technology, specifically relating to an HDAC inhibitor based on a tyrosine backbone, its synthesis method, and its application. The invention uses L-tyrosine as the backbone, with its aromatic ring as the Cap region, linked by a flexible alkyl chain via an ether bond, and terminated by an isohydroxamic acid group (ZBG). The tyrosine backbone provides a rigid structure, reducing entropy loss and enhancing hydrophobic interactions with the HDAC surface. By introducing substituents (such as halogens, methyl groups, etc.) onto the tyrosine benzene ring, the affinity with the HDAC active pocket is further optimized. The prepared compound b19 exhibits an HDAC inhibition capacity of 100%. 50 The concentration reached 26.8 nM, exhibiting superior antitumor activity compared to SAHA, especially against solid tumors such as HeLa cells with IC50. 50 It is 0.55 μM.

The invention relates to protected HDAC inhibitor compounds of formula I, in which Y, Ar1, Ar2, X, R1 and R2 are as defined herein. In aspects, the inventions relates to use of the compounds, and to methods of deprotecting the compounds.

Provided herein are methods of treating and / or managing cancer, comprising administering to a patient Compound A, or an enantiomer or mixture of enantiomers thereof, or a pharmaceutically acceptable salt, solvate, hydrate, co-crystal, clathrate, or polymorph thereof. Additionally, provided herein are methods of treating and / or managing cancer, comprising administering to a patient Compound A, or an enantiomer or mixture of enantiomers thereof, or a pharmaceutically acceptable salt, solvate, hydrate, co-crystal, clathrate, or polymorph thereof, in combination with a second active agent selected from the group consisting of an anti-CD20 antibody, an HDAC inhibitor, a proteasome inhibitor, an anti-CD38 antibody, an anti-SLAMF7 antibody, a nuclear export inhibitor, a BCL-2 inhibitor, and an immune checkpoint inhibitor. Also provided herein are combination therapies for treating and / or managing cancer, further comprising dexamethasone as a third active agent.

The application discloses a kind of hydroxamic acid double-target compound derivatives and application thereof.The double-target derivative designed in the application has obvious inhibitory activity to WDR5 protein and HDAC protein, can be used as WDR5, HDAC double-target inhibitor, is used for treating diseases related to WDR5, HDAC, aims at improving the therapeutic effect of existing HDAC inhibitor.The small molecule shows good activity in various experiments, and is expected to be developed into specific antitumor drugs.

The application discloses a culture medium, a method and a model for constructing polarized 3D human intestinal organoids, and relates to the field of organoid culture. The culture medium comprises 5-15 mu g / mL of Wnt3a, 30-100 mu g / mL of R-spondin-1, R-spondin-2 and / or R-spondin-3, 10-50 nmol of a gamma-secretase inhibitor, 2-10 mu mol of a Wnt agonist, 50-200 mu mol of an HDAC inhibitor, 0.5-2% of an N2 supplement, 1-4% of a B27 supplement, 5-20 mu g / mL of IGF-1, 0.1-2 mu mol of a TGF-beta receptor inhibitor, and the rest is Williams E solution. The model obtained by the application realizes long-term stable mature differentiation state and physiological polarity maintenance.

Provided herein are methods comprising an HDAC inhibitor (HDACi), and / or a PD-L1 and / or a PD-1 inhibitor, and / or a CTLA-4 inhibitor, and / or an anti-cancer agent. Also, provided herein are pharmaceutical compositions suitable for treatment of cancer.

This invention belongs to the field of pharmaceutical preparation technology, specifically relating to an HDAC inhibitor based on a tyrosine backbone, its synthesis method, and its application. The invention uses L-tyrosine as the backbone, with its aromatic ring as the Cap region, linked by a flexible alkyl chain via an ether bond, and terminated by an isohydroxamic acid group (ZBG). The tyrosine backbone provides a rigid structure, reducing entropy loss and enhancing hydrophobic interactions with the HDAC surface. By introducing substituents (such as halogens, methyl groups, etc.) onto the tyrosine benzene ring, the affinity with the HDAC active pocket is further optimized. The prepared compound b19 exhibits an HDAC inhibition capacity of 100%. 50 The concentration reached 26.8 nM, exhibiting superior antitumor activity compared to SAHA, especially against solid tumors such as HeLa cells with IC50. 50 It is 0.55 μM.

Provided are an HDAC inhibitor, and a preparation and use thereof. Specifically, the inhibitor is a compound having a structure as shown in formula I. The compound inhibits histone deacetylase (HDAC) activity, and can be used in the preparation of HDAC inhibitors and / or drugs for treating and / or preventing and / or alleviating malignancies and immune diseases associated with HDAC.

Method for treating Ewing sarcoma in a subject, comprising administering to a subject in need thereof a therapeutically effective amount of (E)-3-(2-(4-(2-fluoro-5-((4-oxo-3,4-dihydrophthalazin-1-yl)methyl)benzoyl)piperazin-1-yl)pyrimidin-5-yl)-N-hydroxyacrylamide, or a pharmaceutically acceptable salt thereof.