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Method for identifying positive allosteric modulators for odorant receptors

An odorant and receptor technology, applied in the field of positive regulator assays, can solve problems such as incomprehension in the field of smell

Pending Publication Date: 2020-04-21
FIRMENICH SA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Such allosteric modulation of odorant receptor activity is speculative at best and poorly understood in the olfactory field

Method used

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  • Method for identifying positive allosteric modulators for odorant receptors
  • Method for identifying positive allosteric modulators for odorant receptors
  • Method for identifying positive allosteric modulators for odorant receptors

Examples

Experimental program
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Embodiment approach

[0151] The assays and methods described herein utilize the relevant human olfactory receptors and / or corresponding mouse orthologs in assays and methods for identifying one or more compounds from a panel of compounds, wherein the One or more compounds positively modulate the activity of an olfactory receptor induced by an agonist odorant compound, wherein the agonist is of particular interest to the fragrance industry and the target receptor, its A combination of an agonist and the one or more compounds.

[0152] The present disclosure provides the identification of compounds that can be used in perfumery applications to modulate, ie enhance, a desired aroma or target agonists, such as musk or floral compounds such as muskone or floral lily-of-the-valley compounds, respectively. In some modalities, the volatile compound that enhances the target agonist is a positive allosteric modulator of the target agonist olfactory receptor. Without being bound by any particular theory, sy...

Embodiment 1

[0356] Example 1: Identification of odorant receptors associated with sensory outcomes.

[0357]Choose from a wide range of target compounds important to the fragrance industry (eg musky, floral or woody ingredients). Methods as described in WO2014 / 210585 can be used to identify a relatively small fraction of the total ORs present in an organism that are specifically activated or inhibited by one or more of these compounds. Transcriptomic analysis (such as NGS methods) or proteomic analysis (such as mass spectrometry) represent additional approaches to identify ORs in vitro. Alternatively, in vivo methods (such as the DREAM method) allow for OR de-orphaning upon gas-phase delivery of volatile compounds [Von Der Weid B. et al., Natureneuroscience, 18(10):1455-63 (2015)].

[0358] Olfactory receptors can be assessed to determine whether psychologic (sensory) outcomes of target compound perception can be correlated with target compound-induced activity in vitro. Such olfactory ...

Embodiment 2

[0359] Example 2: Identification of musk olfactory receptors

[0360] In terms of average odor detection thresholds at the sensory level, the musk compounds muscone, Musk xylene and muskone form a highly related group. To test whether the sensory correlations observed between the four musk compounds were related to the activity of individual odorant receptors, the OR5AN1 olfactory receptor response to musk compounds was assessed. The observed receptor specificity and sensitivity values ​​were compared with human psycho(sensory) odor detection threshold data ( figure 1 ).

[0361] The OR5AN1 olfactory receptor is blocked by muscone, Specific activation by muskxylene and muscone. However, none of the other musk compounds tested could activate the OR5AN1 olfactory receptor. see figure 1 a.

[0362] The observed musk receptors ( figure 1 a) and psychophysical ( figure 1 b) activity ranking is the same, the musk compound has ligand potency (EC for OR5AN1 olfactory recept...

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Abstract

The various aspects presented herein relate to the perfumery industry. More particularly, the various aspects presented herein relate to assays and methods for screening and identifying compositions and / or ingredients that intensify a subject's perception of target odorant compounds based on the use of particular olfactory receptors activated by the target odorant compound.

Description

[0001] Cross References to Related Applications [0002] This application claims U.S. Provisional Patent Application Serial Nos. 62 / 609,004 and 62 / 609,017, filed December 21, 2017, U.S. Provisional Patent Application Serial No. 62 / 781,796, filed December 19, 2018, and Priority of European Patent Application Serial No. 18157690.1 filed on 20 April and European Patent Application Serial No. 18166887.2 filed on April 11, 2018, the entire contents of which are hereby incorporated by reference in their entirety. technical field [0003] The technical field relates to odorants and aroma receptors, and assays that can be used to identify odorants and / or aroma compounds, more particularly positive modulators of human odorant receptor activity. Background technique [0004] Smell is one of the most complex and least understood of the human sensory systems. There are many steps from olfactory receptor (OR) activation to perception that still require further investigation. If we can ...

Claims

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Application Information

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IPC IPC(8): A61Q13/00C07K14/72G01N33/50
CPCC07K14/723G01N33/5008G01N2500/10G01N33/566G01N2333/726G01N33/502
Inventor P·菲斯特M·罗杰斯L·吴C·马格特
Owner FIRMENICH SA
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