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Methods of treating behavior alterations

A behavioral, purposeful technology, applied in the field of therapeutic behavioral change, that addresses unmet problems

Pending Publication Date: 2020-04-10
ORYZON GENOMICS SA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] Therefore, there is a strong and unsatisfied need for new and / or improved drugs for the treatment of behavioral changes, in particular drugs that act through novel mechanisms of action, which allow specific treatment of behavioral changes and / or exhibit greater More favorable side effects of current treatment

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 5

[0047] Example 5 and Figure 5 and Image 6 The utility of KDM1A inhibitors for the treatment of social behavior changes is further illustrated using another widely used social behavior test, the three-compartment test (TCT). TCT is a common method for measuring social behavior in mice and can be used to assess the effects of compound treatments for altered social interaction using animals that exhibit congenital or acquired deficits in social behavior. In the TCT test, as described in more detail in Example 5, after acclimation to the three-chamber arena, mice were released into the middle chamber and allowed to explore the other chambers. In the adjacent "mouse" compartment, a docile stimulus mouse was located in a mesh container, while a similar container was in the other adjacent compartment without stimulation mice (target compartment). The tendency of mice to approach or avoid compartments with stimulation provided a measure of sociability. as in Example 5 and Figur...

Embodiment 1

[0323] Example 1: Materials

[0324] Compound 1 (or Comp.1) is compound 5-((((1R,2S)-2-(4-(benzyloxy)phenyl)cyclopropyl)amino)methyl)-1,3,4- Oxadiazol-2-amine, also known as (-)5-(((((trans)-2-(4-(benzyloxy)phenyl)cyclopropyl)amino)methyl)-1, 3,4-oxadiazol-2-amine, the chemical structure of which is shown below.

[0325]

[0326] This compound can be obtained as disclosed in WO2012 / 013728.

Embodiment 2

[0327] Example 2: In vitro KDM1A inhibition assay

[0328] The inhibitory activity of compounds against KDM1A can be determined using the following methods.

[0329] Human recombinant KDM1A protein (GenBank accession number NM_015013, amino acid 158 terminus with N-terminal GST tag, MW: 103 kDa) was used.

[0330] Serial 3-fold dilutions of test compounds (ranging between 30 μM and 1 nM) were pre-incubated with human recombinant KDM1A enzyme (BPS Bioscience, reference 50100) in assay buffer (50 mM sodium phosphate pH 7.4) for 15 min on ice . Each concentration of inhibitor was tested in duplicate. Via appK in KDM1A M Dimethyl H3K4 peptide substrate (Anaspec, ref. 63677) was added to initiate the enzymatic reaction. After 30 min incubation at 37°C, Amplex red reagent and horseradish peroxidase (HRP) solution were added as recommended by the supplier (Invitrogen) to detect H formed in the enzymatic reaction 2 O 2 . The mixture was incubated for 5 minutes at room tempera...

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PUM

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Abstract

Provided herein are methods for treating behavior alterations using KDM1A inhibitors, particularly 5-((((1R,2S)-2-(4-(benzyloxy)phenyl)cyclopropyl)amino)methyl)-1,3,4-oxadiazol-2-amine.

Description

technical field [0001] The present invention relates to methods for treating behavioral changes. Background technique [0002] Behavioral changes, such as, for example, social withdrawal or aggressive behavior, are so prevalent in today's society that clinicians in their own right consider it a medical condition. Nonetheless, the treatment of behavioral changes remains a medical challenge. There are currently no approved drugs specifically for the treatment of social withdrawal, aggressive behavior, or other behavioral changes. In addition, many of the existing drugs used to treat behavioral change can cause serious side effects. For example, many antipsychotic drugs (also called neuroleptics or strong tranquilizers) used to treat aggressive behavior and other behavioral changes cause sedation. [0003] Therefore, there is a strong and unmet need for new and / or improved drugs for the treatment of behavioral changes, in particular drugs acting through new mechanisms of act...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/44A61P25/00A61P25/24A61P25/16A61P25/14A61P25/28A61P25/18A61P25/30A61P25/08
CPCA61K31/44A61P25/00A61P25/24A61P25/16A61P25/14A61P25/28A61P25/18A61P25/30A61P25/08A61K31/4245A61K9/0053
Inventor 塔玛拉·马埃斯戴维·罗特兰特·波索克里斯蒂安·格里南·费雷梅尔塞·帕利亚斯·利贝里亚罗泽·纳达尔·阿莱马尼安东尼奥·阿尔马里奥·加西亚
Owner ORYZON GENOMICS SA
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