Differentials
To identify the aroma perceptual quality (PQ) of each olfactory receptor,
we formulated isoaromatic mixtures of receptor agonists,
i.e. proportioned in such a way that no ingredient dominates the mixture or is drowned out by the other ingredients,
and smelled them in order that the note encoded by the target receptor would stand out above the other notes.
Doing so has revealed candidate primary odors for
OR52D1 (ethereal/painty),
OR2J2 (soft, mellow, oxidized lemon),
and OR2J3 (sharp, jagged, like cinnamon or black pepper).
However, this is inexact as there is no way to isolate the target receptor from the whole aroma,
and any combinatorial codes involving the target receptor can distract from the observation.
For each receptor that has known antagonists or inverse agonists,
we made the agonist mixture twice and then added antagonists or inverse agonists to one of them,
to create an antagonized mixture.
This makes it possible to isolate the target receptor,
provided the antagonist does not deactivate any unintended receptors activated by the agonist mixture.
The two formulae are smelled one after the other, or in an alternating fashion,
and any aroma notes present in the "plus" (agonist) mixture
and absent in the "minus" (antagonized) mixture are believed to be the result of receptor deactivation,
since the agonist mixture contains no odorants which the antagonized mixture lacks.
These are the odorants we used and the results of our experiment.
In most cases, we've recorded the amount of each odorant used.
In all cases, the +agonist mixture's proportions should be equally intense to the nose of the individual smeller,
and the -antagonized mixture should have only enough antagonist or inverse agonist to perceptibly diminish one aroma note enough to describe it.
In some cases, an other receptor antagonist (ORA) or inverse agonist has been added to reduce contamination of the result by deactivation
of a receptor other than the target.
For purposes of this web page, "inverse agonist" and "antagonist" are considered as equivalent.
| +OR1A1 | Agonists: | dihydrojasmone | |
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hydroxycitronellal | | helional | | estragole 5% in EtOH | | d-limonene | | citronellal natural | |
|
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| -OR1A1 | Antagonists: | 2-ethyl fenchol | |
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methyl pyrazine 0.1% in DPG | | ethyl vanillin 20% in EtOH | | β-damascone | | methyl salicylate | | geranyl acetate | | terpinyl acetate | |
|
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| -OR1A1 mixture odor: | unpleasant cough drop, humus, stale |
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| +OR1A1 mixture odor: | dark green leafy, oregano, cough drops, caraway |
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|
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| Identified OR1A1 PQ: | dark green leafy herbal |
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| +OR1D2 | Agonists: | tetrahydromyrcenol | 0.6 |
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bourgeonal | 0.135 | floralozone | 0.075 |
|
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| -OR1D2 | Antagonists: | undecenal | 0.045 |
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|
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| -OR1D2 mixture odor: | aldehydic, waxy, orange, milky |
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| +OR1D2 mixture odor: | cleaning products, aldehydic, bright, shining |
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|
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| Identified OR1D2 PQ: | clean-bright |
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|
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| Notes: | Undecanal was not available, but undecenal should be similar enough in aroma properties. |
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| +OR1G1 | Agonists: | γ-decalactone | |
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hedione | | octanal | | lyral | | eugenyl acetate | |
|
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| -OR1G1 | Antagonists: | cyclohexanone | |
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|
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| -OR1G1 mixture odor: | chemical, acetone, waxy, vinyl, swimming pool, olives |
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| +OR1G1 mixture odor: | waxy, delicate floral, lactonic, sweet, candy, peach, fruity |
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|
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| Identified OR1G1 PQ: | waxy |
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|
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| Notes: | We have chosen waxy as the aroma note for OR1G1 because the agonist mixture smells more strongly waxy than the antagonized mixture does, and waxy correlates most strongly with OR1G1 agonism in odor descriptions. The descriptors of lactonic, sweet, candy, and fruity do not correlate as well, and many OR1G1 agonists (e.g. lyral) do not smell at all lactonic, sweet, candy-like, or fruity. It is also worth noting that cyclohexanone, the competitive antagonist, is also a weak agonist. |
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| +OR2A25 | Agonists: | geranyl acetate | 20 |
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linalool | 20 |
|
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| -OR2A25 | Antagonists: | methyl salicylate | 3 |
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|
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| -OR2A25 mixture odor: | spearmint, tobacco, smoky |
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| +OR2A25 mixture odor: | tobacco, brown, dried leaves, floral, berry |
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|
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| Identified OR2A25 PQ: | bold-tabagique |
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| +OR2B11 | Agonists: | d-limonene | 15 |
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coumarin 10% in EtOH | 15 | coffee difuran 0.1% | 10 | | ORAs: | propanal 1% in DPG | 10 |
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|
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| -OR2B11 | Antagonists: | ethyl vanillin 20% in EtOH | 10 |
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terpinyl acetate | 5 |
|
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| -OR2B11 mixture odor: | spicy, cinnamon, coffee, bath tissue, medicinal |
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| +OR2B11 mixture odor: | bold, dark brown, coffee, orange, cinnamon |
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|
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| Identified OR2B11 PQ: | bold coffee-like |
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| +OR2L3 | Agonists: | α-terpineol | 15 |
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indole 1% in EtOH | 15 | acetophenone | 2 | | Carriers: | isopropyl myristate | 50 |
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|
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| -OR2L3 | Antagonists: | timberol | 15 |
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|
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| -OR2L3 mixture odor: | woody, pine, fruity, floral, berry, burnt |
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| +OR2L3 mixture odor: | camphorous, citrus, naphthyl |
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|
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| Identified OR2L3 PQ: | camphorous |
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| +OR2W1 | Agonists: | methyl cinnamate | |
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decanol | | cis-3-hexen-1-ol | | methyl salicylate | | benzyl acetate | | hexanal | | | ORAs: | β-damascone | |
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ethyl vanillin | |
|
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| -OR2W1 | Antagonists: | 2-ethyl fenchol | |
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|
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| -OR2W1 mixture odor: | peppermint, humus, cough drop, limnic |
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| +OR2W1 mixture odor: | vegetable, minty, onion, limnic. metallic |
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|
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| Identified OR2W1 PQ: | vegetable-metallic-alliaceous |
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| +OR2W3 | Agonists: | lilial | 20 |
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lyral | 15 | hedione | 5 | β-ionone | 3 | geraniol | 2 | nerol | 2 |
|
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| -OR2W3 | Antagonists: | isovaleric acid 10% in IPM | 3 |
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|
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| -OR2W3 mixture odor: | sweaty, fruity, faint lemon |
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| +OR2W3 mixture odor: | lemon zest, cleaning products, cumin, floral |
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|
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| Identified OR2W3 PQ: | zesty |
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| +OR2AG1 | Agonists: | bean pyrazine 0.1% in DPG | 15 |
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phenirat | 5 | phenethyl acetate | 5 | isoamyl acetate 10% in EtOH | 2 | prenyl acetate | 1 |
|
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| -OR2AG1 | Antagonists: | ethyl pyrazine 10% | 13 |
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|
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| -OR2AG1 mixture odor: | peanut butter and banana sandwich |
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| +OR2AG1 mixture odor: | green stemmy, sharp, banana, rose |
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|
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| Identified OR2AG1 PQ: | stemmy-green |
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| +OR2AG2 | Agonists: | linalool | 15 |
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nerol | 10 | phenylpropyl alcohol | 5 | phenethyl alcohol | 3 | geraniol | 2 | | Carriers: | isopropyl myristate | 50 |
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|
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| -OR2AG2 | Antagonists: | ethyl pyrazine 10% | 7 |
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|
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| -OR2AG2 mixture odor: | floral, rose, lactonic, lemon, cereal, pollen |
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| +OR2AG2 mixture odor: | mustard, floral, pollen, stemmy, rose, lemon |
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|
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| Identified OR2AG2 PQ: | sharp-pollinic |
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|
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| Notes: | There are no known antagonists or inverse agonists for OR2AG2. However, this receptor's high degree of similarity to OR2AG1 may mean it shares the same antagonist. Caution should be used in interpreting these results. |
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| +OR2AT4 | Agonists: | sandalore | |
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brahmanol | |
|
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| -OR2AT4 | Antagonists: | phenirate | |
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raspberry ketone | |
|
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| -OR2AT4 mixture odor: | woody, creamy, raspberry, sandalwood, rose |
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| +OR2AT4 mixture odor: | sharp, sandalwood, sulfurous, pine |
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|
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| Identified OR2AT4 PQ: | gritty |
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|
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| Notes: | The agonist mixture's odor has a grittiness that resembles that of benzyl salicylate. |
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| +OR3A1 | Agonists: | ethanol | 30.4 |
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helional | 10 | lilial | 10 | cyclamal | 5 | trifernal | 0.6 |
|
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| -OR3A1 | Antagonists: | bourgeonal 15% in EtOH | 50 |
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α-methyl cinnamaldehyde 10% in EtOH | 40 |
|
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| -OR3A1 mixture odor: | green, waxy, aldehydic, rotten squash, cinnamon |
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| +OR3A1 mixture odor: | green, cyclamen, alcoholic, rhubarb, wet newspaper |
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|
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| Identified OR3A1 PQ: | cyclamic |
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| +OR4M1 | Agonists: | acetophenone | 35 |
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methyl pyrazine 0.1% in DPG | 20 | | ORAs: | decanal 5% in EtOH | 20 |
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timberol | 8 | | Carriers: | isopropyl myristate | 50 |
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|
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| -OR4M1 | Antagonists: | citronellal natural | 10 |
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|
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| -OR4M1 mixture odor: | chemical, cherry, vinyl, chlorine, burnt |
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| +OR4M1 mixture odor: | chemical, grassy, peanut, vinyl, malty, chlorine, potato skin, grape |
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|
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| Identified OR4M1 PQ: | malty? |
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| +OR5P3 | Agonists: | coumarin 10% in EtOH | 15 |
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d-carvone | 10 | oranger crystals 15% in EtOH | 7 | l-carvone | 2 |
|
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| -OR5P3 | Antagonists: | methyl eugenol | 20 |
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propanal 1% in DPG | 15 |
|
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| -OR5P3 mixture odor: | bready, caraway, bubblegum, minty |
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| +OR5P3 mixture odor: | caraway, hay, acrid, patchouli, burnt plastic, minty |
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|
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| Identified OR5P3 PQ: | patchoulic |
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| +OR8D1 | Agonists: | sotolone 0.1% | 9 |
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heptanoic acid 10% in IPM | 8 | p-cymene | 1 | | Carriers: | isopropyl myristate | 25 |
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|
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| -OR8D1 | Antagonists: | β-damascone | 10 |
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|
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| -OR8D1 mixture odor: | celery, burnt, sweet, herbal, caramellic |
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| +OR8D1 mixture odor: | strong burnt, acrid, caramellic, herbal |
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|
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| Identified OR8D1 PQ: | burnt |
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| +OR8H1 | Agonists: | oranger crystals 15% in EtOH | 3 |
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skatole 1% in EtOH | 1 | | Carriers: | isopropyl myristate | 60 |
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ethanol | 3 |
|
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| -OR8H1 | Antagonists: | strawberry glycidate | 2 |
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|
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| -OR8H1 mixture odor: | strawberry, orange, halitosis, burnt sugar |
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| +OR8H1 mixture odor: | broccoli, mustard, neroli/orangeflower, naphthyl |
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|
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| Identified OR8H1 PQ: | cruciferous |
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| +OR9Q2 | Agonists: | p-cresyl acetate | 0.35 |
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| ORAs: | β-damascone | 1 |
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propanal | 0.04 | | Carriers: | isopropyl myristate | 35 |
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|
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| -OR9Q2 | Antagonists: | bourgeonal 15% in EtOH | 30 |
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nerolidol | 25 | sandranol 10% in EtOH | 3 |
|
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| -OR9Q2 mixture odor: | fresh shorn wool, orange peel, halitosis |
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| +OR9Q2 mixture odor: | horse stable, urinous, plasticky |
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|
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| Identified OR9Q2 PQ: | urinous |
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| +OR10G7 | Agonists: | eugenol | 7 |
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isoeugenol | 5 | eugenyl acetate | 3 | guaiacol | 0.1 | | ORAs: | nerolidol | 2 |
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bourgeonal 15% in EtOH | 2 | | Carriers: | isopropyl myristate | 50 |
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|
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| -OR10G7 | Antagonists: | decanal 5% in EtOH | 20 |
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propanal 1% in DPG | 20 | β-damascone | 2 |
|
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| -OR10G7 mixture odor: | balsamic, clove, orange, bubble gum, rosin, corn, buttery |
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| +OR10G7 mixture odor: | clove, pine, rosin, urinous |
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|
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| Identified OR10G7 PQ: | rosinous |
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| +OR11A1 | Agonists: | geosmin 10% in DPG | 10 |
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2-ethyl fenchol | 5 | | Carriers: | isopropyl myristate | 50 |
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|
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| -OR11A1 | Antagonists: | allyl phenoxyacetate | 15 |
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|
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| -OR11A1 mixture odor: | humus, honey, earthy, pruny |
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| +OR11A1 mixture odor: | green, humus, limnic, chalky, earthy, watery |
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|
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| Identified OR11A1 PQ: | watery |
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|
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| Notes: | Allyl phenylacetate was not available so it is hoped that allyl phenoxyacetate would also be an inverse agonist. |
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| +OR51E1 | Agonists: | methyl eugenol | |
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butyl butyryl lactate | | eugenyl acetate | | methyl salicylate | |
|
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| -OR51E1 | Antagonists: | florhydral | |
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bourgeonal | |
|
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| -OR51E1 mixture odor: | bubble gum, muguet, waxy, floral, sweet, rose, juicy |
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| +OR51E1 mixture odor: | dairy, cheesy, sweaty, minty, clove |
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|
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| Identified OR51E1 PQ: | dairy |
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| +OR51E2 | Agonists: | β-ionone | 20 |
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propionic acid 5% in IPM | 15 | | Carriers: | isopropyl myristate | 50 |
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|
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| -OR51E2 | Antagonists: | decyl acetate | 40 |
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|
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| -OR51E2 mixture odor: | floral, sour, waxy, violet, berry |
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| +OR51E2 mixture odor: | vinegar, waxy, plastic |
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|
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| Identified OR51E2 PQ: | acetic |
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|
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| Notes: | Lee et al 2023 identified C-11 acetate as competitively binding to OR51E2 (https://doi.org/10.3390%2Fbiomedicines11061688), however we were not able to obtain this compound, so we used C-10 acetate instead which should function similarly. |
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| +OR51I2 | Agonists: | delta-decalactone | 25 |
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caproic acid | 0.1 | | Carriers: | isopropyl myristate | 30 |
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|
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| -OR51I2 | Antagonists: | lilial | 15 |
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cyclamal | 10 |
|
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| -OR51I2 mixture odor: | aldehydic, clean, peach, new rubber balloon, waxy |
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| +OR51I2 mixture odor: | peach, old rubber balloon, juicy, waxy |
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|
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| Identified OR51I2 PQ: | peach-cheddar juicy |
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|
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| Notes: | OR51I2 was unintentionally included in a previous formulation of the OR51E1 differential, and revealed for the two receptors in combination a powdered cheddar note. |
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| +OR51L1 | Agonists: | allyl phenoxyacetate | |
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caproic acid | | | ORAs: | ethyl vanillin | |
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2-ethyl fenchol | |
|
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| -OR51L1 | Antagonists: | florhydral | |
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bourgeonal | |
|
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| -OR51L1 mixture odor: | watery, honey, sweet, waxy, cocoa, moldy |
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| +OR51L1 mixture odor: | cloying, molasses, honey, cocoa, sweet |
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|
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| Identified OR51L1 PQ: | syrupy |
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|
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| Notes: | Allyl phenylacetate was not available so it is hoped that allyl phenoxyacetate would also be a strong agonist. Only a very small amount of caproic acid was used to avoid the mixture smelling sweaty. When made without the OR1A1 inverse agonists (ethyl vanillin and 2-ethyl fenchol), the differential note is strongly pruny. |
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| +TAAR5 | Agonists: | triethylamine | |
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| Carriers: | isopropyl myristate | |
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|
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| -TAAR5 | Antagonists: | timberol | |
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|
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| -TAAR5 mixture odor: | burned fish, breaded seafood, ammonia, woody, rotten |
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| +TAAR5 mixture odor: | shrimp, prawns, rotting seafood, paper mill |
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|
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| Identified TAAR5 PQ: | prawny |
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|
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| Notes: | The known TAAR5 agonist trimethylamine (TMA) was unavailable, however TEA has a very similar odor and molecular structure. |
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