AG1529
AG1529 is a TRPV1 inhibitor and capsaicinoid-based soft agent with a human TRPV1 IC50 of 0.9-0.93 μM. AG1529 reversibly blocks capsaicin-evoked TRPV1 activation, binds to the TRPV1 capsaicin binding site, moderately affects pH-induced TRPV1 gating, and does not alter voltage- or heat-mediated TRPV1 responses. AG1529 suppresses TRPV1-mediated neuronal excitability, reduces capsaicin- and pH-evoked neuronal firing, abolishes histaminergic and inflammation-mediated TRPV1 sensitization. AG1529 exhibits anti-nociceptive and antipruritic effects, attenuates in vivo hyperalgesia and pruritus, dose-dependently reduces acute histaminergic itch in rodents, and mildly blocks hTRPA1 and hTRPM8 channel activity. AG1529 undergoes hydrolysis and dermal deactivation, minimizes TRPV1-associated side reactions, does not evoke capsaicin-like burning sensation, and does not disrupt physiological thermal regulation. AG1529 can be used for the research of inflammatory cutaneous nociception and acute histaminergic pruritus.
For research use only. We do not sell to patients.
- CAS No.: 2225980-49-2
- Formula: C22H34INO5
- Molecular Weight:519.41
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
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TRPV1 0.93 μM (IC50) |
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Cell Line
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Type | Value | Description | References |
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| SH-SY5Y | IC50 |
0.86 μM
Compound: 37
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Antagonist activity at rat TRPV1 expressed in human SH-SY5Y cells assessed as reduction in capsaicin-induced intracellular calcium accumulation preincubated with cells followed by capsaicin addition by Fluo-4 NW dye based fluorescence assay
Antagonist activity at rat TRPV1 expressed in human SH-SY5Y cells assessed as reduction in capsaicin-induced intracellular calcium accumulation preincubated with cells followed by capsaicin addition by Fluo-4 NW dye based fluorescence assay
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[PMID: 30783490] |
AG1529 (1-100 μM) potently antagonizes TRPV1 in SH-SY5Y cells stably expressing TRPV1 with an IC50 of 0.93 μM[1].
AG1529 is highly stable in HaCaT homogenate (25 μM; 240 min), moderately stable in human plasma (100 μM; 20 min), and completely hydrolyzed in human liver S9 fraction (50 μM; 60 min) under the tested conditions[1].
AG1529 (50 μM; 120 min) is significantly hydrolyzed in primary adult human epidermal keratinocyte and dermal fibroblast homogenates, with only 22.6% and 13.3% residual substrate remaining after 120 min, respectively[1].
AG1529 (0.2 mg/mL) is hydrolyzed by both hCE1 and hCE2, with preferential metabolism by hCE2 as indicated by its higher intrinsic clearance and shorter half-life with this isoform[1].
AG1529 (1 μM) reversibly and competitively blocks capsaicin-activated hTRPV1 in HEK293 cells with an IC50 of 0.9 μM[2].
AG1529 (1-10 μM; 30 s) moderately blocks pH-induced activation of hTRPV1 in HEK293 cells at 10 μM, but does not significantly affect voltage- or heat-mediated hTRPV1 gating at tested concentrations[2].
AG1529 (10 μM; 30 s) moderately inhibits menthol-activated hTRPM8 and AITC-activated hTRPA1 in HEK293 cells at 10 μM, with significantly lower efficacy than its inhibition of hTRPV1[2].
AG1529 binds to the capsaicin binding site of TRPV1 in a conformation similar to capsaicin, supporting its mechanism as a competitive TRPV1 antagonist, while steric hindrance in TRPA1 reduces its binding affinity for that channel[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
| Species | Dose | Route | T1/2 | Tmax | Cmax | AUClast | AUCinf |
|---|---|---|---|---|---|---|---|
| Mice[2] | 5 mg/kg | i.v. | 3.6 min | 5.0 min | 738.1 ng/mL | 14709.3 min·ng/mL | 14728.5 min·ng/mL |
AG1529 (1-10 mg/kg; i.v.; single dose) produces a transient, dose-dependent reversal of CFA-induced thermal hyperalgesia without affecting contralateral thermal nociception[1].
AG1529 (100 μg; i.pl.; single dose; 30 minutes prior to histamine) significantly reduces histaminergic pruritus in mice, with peak effects observed 10-20 minutes after histamine injection[1].
AG1529 (100 μg; i.pl.; single dose; 30 minutes prior to chloroquine) significantly reduces non-histaminergic pruritus in mice, with peak effects observed 5-15 minutes after chloroquine injection[1].
AG1529 (10 mg/kg; i.v.; single dose) does not affect body temperature in mice, avoiding the hyperthermia side effect associated with other TRPV1 antagonists[1].
AG1529 (0.1-1% w/v; topical wipe; single application) dose-dependently reduces histamine-induced pruritus in rats, with 1% AG1529 producing the greatest attenuation of scratching behavior[2].
AG1529 (0.1-1% w/w; topical application; twice daily; 3 days) significantly reduces histamine-induced pruritus in rats, with 1% AG1529 completely eliminating scratching behavior[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:unspecified[1]
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Dosage:10 μg; 30 μg; 100 μg
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Administration:i.pl.; single dose
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Result:Ablated CFA-induced thermal hyperalgesia in the ipsilateral paw in a dose-dependent and transient manner.
Showed anti-hyperalgesic activity at 30 minutes, peaked at 60 minutes, and lasted for 90 minutes at the 100 μg dose.
Did not affect thermal nociception in the contralateral paw.
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Animal Model:unspecified[1]
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Dosage:1 mg/kg; 3 mg/kg; 10 mg/kg
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Administration:i.v.; single dose
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Result:Attenuated CFA-induced thermal hyperalgesia in the ipsilateral paw in a dose-dependent and transient manner.
Showed anti-hyperalgesic effects at 30 minutes, lasting 60 minutes at the 1 mg/kg dose.
Showed effects at 60 minutes, lasting 90 minutes at the 3 mg/kg dose.
Showed significant effects only at 60 minutes at the 10 mg/kg dose.
Did not affect thermal nociception in the contralateral paw.
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Animal Model:unspecified[1]
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Dosage:100 μg
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Administration:i.pl.; single dose; 30 minutes prior to histamine
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Result:Attenuated histamine-induced paw licking time, with statistically significant reductions in the 10-15 minute and 15-20 minute intervals after histamine instillation.
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Animal Model:unspecified[1]
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Dosage:100 μg
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Administration:i.pl.; single dose; 30 minutes prior to chloroquine
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Result:Reduced chloroquine-induced paw licking time, with statistically significant reductions in the 5-10 minute and 10-15 minute intervals after chloroquine instillation.
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Animal Model:unspecified[1]
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Dosage:10 mg/kg
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Administration:i.v.; single dose
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Result:Did not alter mouse body temperature over the 120-minute observation period, unlike the positive control TRPV1 antagonist BCTC which induced significant hyperthermia.
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Animal Model:Wistar (adult, 100-125 g, pruritus model via subcutaneous histamine injection)[2]
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Dosage:0.1% w/v; 1% w/v
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Administration:topical wipe; single application
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Result:Significantly reduced histamine-induced licking time across all 10-minute intervals from 0-60 minutes post-histamine injection.
Produced a dose-dependent reduction in total scratching counts over 60 minutes: 0.1% AG1529 reduced scratching compared to vehicle (p = 0.0003), and 1% AG1529 produced an even greater reduction (p < 0.0001 vs vehicle; p = 0.0395 vs 0.1% AG1529).
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Animal Model:Wistar (adult, 100-125 g, pruritus model via subcutaneous histamine injection)[2]
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Dosage:0.1% w/w; 1% w/w
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Administration:topical application; twice daily; 3 days
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Result:Significantly reduced histamine-induced licking time across all 10-minute intervals from 0-60 minutes post-histamine injection, with the 1% dose nearly eliminating licking activity in most intervals.
Reduced total scratching counts over 60 minutes: 0.1% AG1529 reduced scratching compared to vehicle (p = 0.0122), and 1% AG1529 fully abrogated scratching behavior (p = 0.0003 vs vehicle).
Chemical Information
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CAS No. 2225980-49-2
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Molecular Weight 519.41
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Formula C22H34INO5
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SMILES
O=C(CCCCCCCCCCC)OCC(NCC1=C(I)C=C(O)C(OC)=C1)=O
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
[1]. Serafini M, et al. Targeting Transient Receptor Potential Vanilloid 1 (TRPV1) Channel Softly: The Discovery of Passerini Adducts as a Topical Treatment for Inflammatory Skin Disorders. J Med Chem. 2018;61(10):4436-4455. [Content Brief]
[2]. Nikolaeva-Koleva M, et al. A capsaicinoid-based soft drug, AG1529, for attenuating TRPV1-mediated histaminergic and inflammatory sensory neuron excitability. Sci Rep. 2021;11(1):246. Published 2021 Jan 8. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
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