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| 25mg |
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| 50mg |
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| 100mg |
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Purity: ≥98%
Capsazepine is a novel, potent and synthetic antagonist of TRPM8 channels (IC50 = 562 nM) with potential anticancer activity. A major problem in clinical trials of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) as cancer therapy is the development of resistance to TRAIL. Therefore, agents that can overcome TRAIL resistance have great therapeutic potential. Capsazepine, as a TRPV1 antagonist, has ability to sensitize human colon cancer cells to TRAIL-induced apoptosis. Capsazepine potentiated the effect of TRAIL, as shown by its effect on intracellular esterase activity; activation of caspase-8,-9, and -3; and colony-formation assay. Capsazepine induced death receptors (DRs) DR5 and DR4, but not decoy receptors, at the transcriptional level and in a non-cell-type-specific manner. It blocks the painful sensation of heat caused by capsaicin (the active ingredient of chilli pepper) which activates the TRPV1 ion channel. It is therefore considered to be a capsaicin antagonist.
| Targets |
TRPV1 receptor[1]
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| ln Vitro |
The upregulation of death receptors (DRs) is optimally enhanced by capsazepine (50 μM) without compromising the viability of HCT116 cells. In HCT116 cells, capsazepine (30-50 μM) causes the generation of ROS, and ROS mediate the upregulation of DR5 caused by capsazepine[1]. In 45 minutes of preincubation, capsazepine (1–100 μM) inhibits the release of CGRP–LI when evoked. In rat soleus muscle, capsazepine (3-100 μM) inhibits the release of CGRP-LI when exposed to low pH and capsaicin at concentrations that do not impact the release elicited by KCl. A nonspecific inhibitory effect on CGRP-LI release from the peripheral endings of the capsaicin-sensitive primary afferent neurone is produced by capsazepine (3-100 μM, without 10 μM)[2].
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| ln Vivo |
During endotoxemia, capsazepine (15 mg/kg, sc) reduces the increase in tissue damping and stops the respiratory system from becoming more resistant. Capsazepine lessens lung damage as shown by a decrease in the area of the lung parenchyma that collapses when exposed to LPS[3].
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| Enzyme Assay |
1. We have determined the effect of the competitive antagonist capsazepine at the capsaicin receptor on the release of calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) from rat isolated soleus muscle induced by capsaicin (1 microM), by superfusion with low pH medium (pH 5) or by KCl (80 mM). 2. Each one of the three stimuli tested produced a marked CGRP-LI release. Total evoked release (fmol g-1) was 482 +/- 69, 169 +/- 20 and 253 +/- 43 for capsiacin, low pH medium and KCL, respectively. 3. Prior application of capsiacin (10 microM for 30 min followed by 30 min of washout) to produce capasaicin desensitization in vitro abolished CGRP-LI release induced by the three stimuli. 4. Capsazepine (1-100 microM, 45 min preincubation) inhibited the evoked CGRP-LI release. Capsaicin-induced release was significantly inhibited by 77, 92 and 96% with 10, 30 and 100 microM capsazepine, respectively. Low pH-induced release was inhibited by 78, 84, 88 and 93% with 3, 10, 30 and 100 microM capsazepine, respectively. KCl-induced release was significantly inhibited by 55 and 93% with 30 and 100 microM (but not with 10 microM) capsazepine, respectively. 5. These findings demonstrate that capsazepine prevents low pH- and capsaicin-induced CGRP-LI release from rat soleus muscle at concentrations which do not affect the release evoked by KCl. These findings imply a relationship between the action of low pH and activation of the capsaicin receptor. At high concentrations, capsazepine produces a nonspecific inhibitory effect on CGRP-LI release from peripheral endings of the capsaicin-sensitive primary afferent neurone.[2]
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| Cell Assay |
In this study, we evaluated capsazepine, a TRPV1 antagonist, for its ability to sensitize human colon cancer cells to TRAIL-induced apoptosis. Capsazepine potentiated the effect of TRAIL, as shown by its effect on intracellular esterase activity; activation of caspase-8,-9, and -3; and colony-formation assay. Capsazepine induced death receptors (DRs) DR5 and DR4, but not decoy receptors, at the transcriptional level and in a non-cell-type-specific manner. DR induction was dependent on CCAAT/enhancer-binding protein homologous protein (CHOP), as shown by (a) the induction of CHOP by capsazepine and (b) the abolition of DR- and potentiation of TRAIL-induced apoptosis by CHOP gene silencing. CHOP induction was also reactive oxygen species (ROS)-dependent, as shown by capsazepine's ability to induce ROS and by the quenching of ROS by N-acetylcysteine or glutathione, which prevented induction of CHOP and DR5 and consequent sensitization to TRAIL. Capsazepine's effects appeared to be mediated via JNK, as shown by capsazepine's ability to induce JNK and by the suppression of both CHOP and DR5 activation by inhibition of JNK. Furthermore, ROS sequestration abrogated the activation of JNK. Finally, capsazepine downregulated the expression of various antiapoptotic proteins (e.g., cFLIP and survivin) and increased the expression of proapoptotic proteins (e.g., Bax and p53). Together, our results indicate that capsazepine potentiates the apoptotic effects of TRAIL through downregulation of cell survival proteins and upregulation of death receptors via the ROS-JNK-CHOP-mediated pathway.[1]
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| Animal Protocol |
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| References |
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| Additional Infomation |
Capsazepine is a benzazepine that is 2,3,4,5-tetrahydro-1H-2-benzazepine which is substituted by hydroxy groups at positions 7 and 8 and on the nitrogen atom by a 2-(p-chlorophenyl)ethylaminothiocarbonyl group. A synthetic analogue of capsaicin, it was the first reported capsaicin receptor antagonist. It has a role as a capsaicin receptor antagonist. It is a member of catechols, a member of thioureas, a benzazepine and a member of monochlorobenzenes.
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| Molecular Formula |
C19H21CLN2O2S
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| Molecular Weight |
376.90
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| Exact Mass |
376.101
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| Elemental Analysis |
C, 60.55; H, 5.62; Cl, 9.41; N, 7.43; O, 8.49; S, 8.51
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| CAS # |
138977-28-3
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| Related CAS # |
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| PubChem CID |
2733484
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| Appearance |
Typically exists as Off-white to yellow solids at room temperature
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
581.1±60.0 °C at 760 mmHg
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| Melting Point |
155-157°C
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| Flash Point |
305.3±32.9 °C
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| Vapour Pressure |
0.0±1.7 mmHg at 25°C
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| Index of Refraction |
1.672
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| LogP |
3.5
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
25
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| Complexity |
445
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| Defined Atom Stereocenter Count |
0
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| SMILES |
ClC1C([H])=C([H])C(=C([H])C=1[H])C([H])([H])C([H])([H])N([H])C(N1C([H])([H])C2=C([H])C(=C(C([H])=C2C([H])([H])C([H])([H])C1([H])[H])O[H])O[H])=S
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| InChi Key |
DRCMAZOSEIMCHM-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C19H21ClN2O2S/c20-16-5-3-13(4-6-16)7-8-21-19(25)22-9-1-2-14-10-17(23)18(24)11-15(14)12-22/h3-6,10-11,23-24H,1-2,7-9,12H2,(H,21,25)
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| Chemical Name |
N-[2-(4-chlorophenyl)ethyl]-7,8-dihydroxy-1,3,4,5-tetrahydro-2-benzazepine-2-carbothioamide
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5 mg/mL (13.27 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 5 mg/mL (13.27 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. View More
Solubility in Formulation 3: ≥ 2.87 mg/mL (7.61 mM) (saturation unknown) in 5% DMSO + 40% PEG300 + 5% Tween80 + 50% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: ≥ 2.87 mg/mL (7.61 mM) (saturation unknown) in 5% DMSO + 95% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. 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. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6532 mL | 13.2661 mL | 26.5322 mL | |
| 5 mM | 0.5306 mL | 2.6532 mL | 5.3064 mL | |
| 10 mM | 0.2653 mL | 1.3266 mL | 2.6532 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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