AG1529 (1-100 μM) effectively antagonized TRPV1 in SH-SY5Y cells that stably expressed TRPV1, with an IC50 value of 0.93 μM[1]. Under the test conditions, AG1529 was highly stable in HaCaT cell 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)[1]. AG1529 (50 μM; 120 min) was significantly hydrolyzed in primary adult human epidermal keratinocyte and dermal fibroblast homogenates, with only 22.6% and 13.3% of the substrate remaining after 120 min, respectively[1]. AG1529 (0.2 mg/mL) can be hydrolyzed by both hCE1 and hCE2, but hCE2 has a higher priority in its metabolism, as evidenced by its higher intrinsic clearance and shorter half-life [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 hTRPV1 activation in HEK293 cells at a concentration of 10 μM, but has no significant effect on voltage- or heat-mediated hTRPV1 gating within the tested concentration range [2]. AG1529 (10 μM; 30 s) at a concentration of 10 μM showed moderate inhibitory effects on menthol-activated hTRPM8 and AITC-activated hTRPA1 in HEK293 cells, but its inhibitory efficacy against hTRPV1 was significantly lower than that against hTRPV1[2]. AG1529 binds to the capsaicin binding site of TRPV1 in a conformation similar to capsaicin, which supports its mechanism of action as a competitive antagonist of TRPV1, while steric hindrance in TRPA1 reduces its binding affinity to this channel[2].

AG1529 (10-100 μg; subcutaneous injection; single dose) transiently and dose-dependently reverses CFA-induced thermal hyperalgesia without affecting contralateral thermal pain [1]. AG1529 (1-10 mg/kg; intravenous injection; single dose) transiently and dose-dependently reverses CFA-induced thermal hyperalgesia without affecting contralateral thermal pain [1]. AG1529 (100 μg; subcutaneous injection; single dose; 30 minutes before histamine injection) significantly reduces histaminergic pruritus in mice, with peak effect occurring 10-20 minutes after histamine injection [1]. AG1529 (100 μg; subcutaneous injection; single dose; 30 minutes before chloroquine injection) significantly reduces non-histaminergic pruritus in mice, with peak effect occurring 5-15 minutes after chloroquine injection [1]. AG1529 (10 mg/kg; intravenous injection; single dose) did not affect body temperature in mice, avoiding the hyperthermia side effect associated with other TRPV1 antagonists [1]. AG1529 (0.1–1% w/v; topical application; single dose) reduced histamine-induced pruritus in rats in a dose-dependent manner, with 1% AG1529 showing the strongest inhibitory effect on scratching behavior [2]. AG1529 (0.1–1% w/w; topical application; twice daily for 3 consecutive days) significantly reduced histamine-induced pruritus in rats, with 1% AG1529 completely eliminating scratching behavior [2].

Animal/Disease Models:Unspecified [1]
Doses: 10 μg; 30 μg; 100 μg
Route of Administration: Plantar injection; Single dose
Experimental Results: Thermal hyperalgesia induced by Freund's complete adjuvant (CFA) in the ipsilateral paw was eliminated in a dose-dependent and transient manner. At a dose of 100 μg, anti-hyperalgesic activity was observed at 30 minutes, peaked at 60 minutes, and lasted for 90 minutes. No effect was observed on thermal hyperalgesia in the lateral paw.

---

Animal/Disease Models:Unspecified [1]
Doses: 1 mg/kg; 3 mg/kg; 10 mg/kg
Route of Administration: Intravenous injection; single dose
Experimental Results: Reduced CFA-induced thermal hyperalgesia in the ipsilateral paw in a dose-dependent and transient manner. The 1 mg/kg dose group showed an anti-hyperalgesic effect at 30 minutes, lasting 60 minutes. The 3 mg/kg dose group showed an effect at 60 minutes, lasting 90 minutes. The 10 mg/kg dose group showed a significant effect only at 60 minutes. No effect on thermal hyperalgesia in the lateral paw.

---

Animal/Disease Models:Unspecified [1]
Doses: 100 μg
Route of Administration: Subcutaneous injection; single dose; 30 minutes before histamine administration
Experimental Results: Reduced histamine-induced paw-licking time, with statistically significant reductions in paw-licking time at intervals of 10-15 minutes and 15-20 minutes after histamine infusion.

---

Animal/Disease Models:Unspecified [1]
Doses: 100 μg
Route of Administration: Subcutaneous injection; single dose; 30 minutes before chloroquine administration
Experimental Results: Chloroquine induced a reduction in paw licking time, with statistically significant reductions in paw licking time at intervals of 5-10 minutes and 10-15 minutes after chloroquine infusion.

---

Animal/Disease Models:Unspecified [1]
Doses: 10 mg/kg
Route of Administration: Intravenous injection; single dose
Experimental Results: No change in body temperature of mice during the 120-minute observation period, unlike the positive control TRPV1 antagonist BCTC which caused significant hyperthermia.

---

Animal/Disease Models:Wistar (adult, 100-125 g, pruritus model established by subcutaneous injection of histamine) [2]
Doses: 0.1% w/v; 1% w/v
Route of Administration: local wiping; single administration
Experimental Results: Histamine significantly reduced the time of licking induced by histamine within 0-60 minutes after injection, at all 10-minute intervals. The total number of scratches decreased in a dose-dependent manner within 60 minutes: the number of scratches was significantly reduced with 0.1% AG1529 compared to the solvent group (p = 0.0003), while the reduction effect of 1% AG1529 was more significant (p < 0.0001 compared to the solvent group; p = 0.0395 compared to the 0.1% AG1529 group).

---

Animal/Disease Models:Wistar (adult, 100-125 g, pruritus model established by subcutaneous injection of histamine) [2]
Doses: 0.1% w/w; 1% w/w
Route of Administration: Topical application; twice daily for 3 days
Experimental Results: Histamine-induced licking time was significantly reduced in all 10-minute intervals within 0-60 minutes after injection, with the 1% dose group almost completely eliminating licking behavior in most intervals. Total number of scratches reduced within 60 minutes: The number of scratches was reduced in the 0.1% AG1529 group compared with the solvent control group (p = 0.0122), while the scratching behavior was completely eliminated in the 1% AG1529 group compared with the solvent control group (p = 0.0003).

[1]. 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.

[2]. 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.

C22H34INO5

519.41

2225980-49-2

Typically exists as solids at room temperature

O=C(CCCCCCCCCCC)OCC(NCC1=C(I)C=C(O)C(OC)=C1)=O

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

---

Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

View More

Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

---

Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

View More

Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

---

Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

---

 (Please use freshly prepared in vivo formulations for optimal results.)