| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
Endoplasmic reticulum calcium ATPases (ECAs). [1]
Cyclopiazonic acid targets the sarco/endoplasmic reticulum calcium ATPase (SERCA) pump, an enzyme that transports calcium ions from the cytosol into the endoplasmic reticulum. By acting as a potent and selective inhibitor of SERCA, CPA prevents the reuptake of calcium into the endoplasmic reticulum, leading to depletion of intracellular calcium stores and activation of store-operated calcium entry. This mechanism makes CPA a valuable tool for studying calcium signaling, muscle contraction, and cell physiology. |
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| ln Vitro |
In vitro, Cyclopiazonic acid is a potent inhibitor of SERCA with an IC₅₀ in the low micromolar range. It depletes intracellular calcium stores in various cell types, leading to the activation of calcium-dependent signaling pathways. CPA is used to study the role of calcium in muscle contraction, neurotransmitter release, and cell proliferation. It is a standard tool in calcium signaling research.
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| ln Vivo |
CPA production correlates with niche adaptation: kernel-colonizing A. flavus isolates produced >50 μg CPA/ml culture (average >200 μg/ml), while soil-restricted isolates produced none or low amounts. CPA levels in kernel isolates were 3- to 30-fold equivalent to concentrations cytotoxic in three plant species. [1]
Knockout mutants in CPA biosynthesis (pks-nrps, dmaT, maoA) were less infective in field inoculation tests on maize, showing reduced aflatoxin contamination and less visible fungal growth compared to the wild-type parent. [1] In developing maize seeds, CPA accumulation was greater in kernels infected by virulent isolates (G14 and G25) at approximately 350 μg/g dry mass of kernel powder. [1] Maize inbreds showed diverse sensitivity to CPA-induced cell death in a seedling root assay. Inbreds susceptible to ear rot (e.g., B73 and Va35) were highly CPA-sensitive, while resistant inbreds (e.g., Mp717 and NC358) were CPA-tolerant. CPA sensitivity correlated with silk resistance to A. flavus colonization (Pearson r=0.67, p=0.004) and with aflatoxin contamination levels (Pearson R=0.74, p<0.0003). [1] In vivo, Cyclopiazonic acid is a mycotoxin that can cause toxic effects in animals. It has been associated with various toxicities, including gastrointestinal, neurological, and cardiovascular effects. As a research tool, it is used to study the role of SERCA and calcium signaling in physiological and pathological processes. It is not used therapeutically. |
| Enzyme Assay |
In vitro SERCA enzyme assays for Cyclopiazonic acid involve measuring the ATP-dependent calcium uptake into microsomal vesicles. The enzyme is incubated with ATP and calcium in the presence of varying concentrations of CPA, and the amount of calcium taken up is measured using radioactive calcium (⁴⁵Ca) or fluorescent calcium indicators. IC₅₀ values are calculated from dose-response curves.
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| Cell Assay |
In vitro cell-based assays for Cyclopiazonic acid are performed using various cell types, including muscle cells, neurons, and non-excitable cells. Cells are cultured in appropriate media and treated with CPA at various concentrations. Intracellular calcium levels are measured using fluorescent indicators (e.g., Fura-2, Fluo-4). The effects on cell viability, proliferation, and signaling pathways are assessed. CPA is used to study the role of intracellular calcium stores in various cellular processes.
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| Animal Protocol |
CPA tolerance screen: Roots of 3-4 day old maize seedlings (radicle 3-4 cm long) were exposed to 15 mL of 20 μM CPA for approximately 18 hours at 28°C. Control had DMSO (solvent for CPA stock) plus 0.1 mg/mL ascorbic acid to prevent oxidation. After 12 hours, visible cell death indicated by root browning. Roots were stained with Evans Blue, destained in 0.1 mM CaCl2 for 24 hours, then Evans Blue was extracted from root tips (1-1.5 cm from apex) by macerating in 1% SDS, and absorbance was read at 600 nm. Normalized absorbance = (A600/root tip in treated) - (A600/root tip in control). Broad sense heritability H^2=0.75. [1]
Field testing of CPA mutants: In 2015, sweetcorn line (cv. Miracle) was grown. Ears with yellowing silks (7-10 days after silk emergence) were inoculated by spraying ~1 mL of 10^7/mL conidial suspension to completely cover silks. Ears harvested at maturity, dried to <10% moisture, seeds milled, and 20 g aliquot used for aflatoxin determination by HPLC. In 2016, repeated with seed corn hybrid (25BHR26) using >100 ears per A. flavus line, pooled into 6 replicates. [1] Gene expression analysis in infected kernels: Developing maize seeds (cv. Golden Nuggets) at blister stage were pin-inoculated with conidial suspensions (10^6/mL in 0.001% SDS) or carrier control. Seeds harvested after 4 days, frozen in liquid N2, ground to powder. RNA extracted using TRlzol, DNase digested, purified using silica columns. RT-qPCR performed using 5 ng total RNA and specific primers. Fungal biomass estimated by qPCR of A. flavus histone H4 gene copy number. [1] In vivo animal studies for Cyclopiazonic acid are primarily toxicological, as it is a mycotoxin. Animals are administered CPA orally or via injection, and the effects on various organ systems are assessed. The compound's toxic effects, including gastrointestinal, neurological, and cardiovascular effects, are studied to understand the mechanisms of CPA toxicity. |
| ADME/Pharmacokinetics |
Specific pharmacokinetic properties of Cyclopiazonic acid, such as half-life and bioavailability, are not extensively characterized. As a mycotoxin, it is absorbed from the gastrointestinal tract and distributed to various tissues. It is metabolized in the liver and excreted in urine and feces. Its toxicokinetic profile is studied in the context of mycotoxin exposure.
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| Toxicity/Toxicokinetics |
Cyclopiazonic acid is a mycotoxin with significant toxicity. It can cause gastrointestinal, neurological, and cardiovascular effects in animals. It is a potent SERCA inhibitor and should be handled with extreme caution. It is not intended for human or veterinary use. Proper safety precautions, including the use of personal protective equipment, should be followed when handling this compound.
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| References | |
| Additional Infomation |
CPA is a specific inhibitor of endoplasmic reticulum (ER)-type Ca2+ ATPases (ECAs) in many taxa, including plants. It binds directly and inactivates ECA proteins, leading to unmitigated rise in cytosolic Ca2+ and induction of plant cell death. CPA is produced by A. flavus via a short pathway driven by three enzymes: polyketide synthase-nonribosomal peptide synthetase (PKS-NRPS), O-dimethylallyl tryptophan synthase (DMAT), and monoamine oxidase (MAOA). Unlike aflatoxin, CPA synthesis is stable or enhanced under conditions relevant to field infection, including high temperature. In A. flavus, loss of LaeA or VeA leads to loss of CPA production. A. parasiticus lacks a functional CPA biosynthesis gene cluster. CPA production in A. flavus isolates correlates with ability to infect maize. A seedling root CPA sensitivity assay was developed as a screen for maize germplasm resistance to Aspergillus ear rot. [1]
Cyclopiazonic acid is a mycotoxin produced by Aspergillus and Penicillium species. It is a potent and selective inhibitor of the SERCA pump, making it a valuable research tool for studying calcium signaling and muscle contraction. CPA is used to deplete intracellular calcium stores and study the role of calcium in various cellular processes. This product is for research use only. |
| Molecular Formula |
C20H20N2O3
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|---|---|
| Molecular Weight |
336.3844
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| Exact Mass |
1027.329
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| CAS # |
18172-33-3
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| Appearance |
Off-white to yellow solid powder
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| Density |
1.5±0.1 g/cm3
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| Boiling Point |
598.6ºC at 760mmHg
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| Melting Point |
245-246ºC
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| Flash Point |
315.8ºC
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| Index of Refraction |
1.626
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| LogP |
2.96
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| InChi Key |
SZINUGQCTHLQAZ-DQYPLSBCSA-N
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| InChi Code |
InChI=1S/C20H20N2O3/c1-9(23)14-18(24)17-16-11-8-21-13-6-4-5-10(15(11)13)7-12(16)20(2,3)22(17)19(14)25/h4-6,8,12,16-17,21,24H,7H2,1-3H3/t12-,16+,17+/m1/s1
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| Chemical Name |
(6aR,11aS,11bR)-10-acetyl-11-hydroxy-7,7-dimethyl-2,6,6a,7,11a,11b-hexahydro-9H-pyrrolo[1',2':2,3]isoindolo[4,5,6-cd]indol-9-one
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| Synonyms |
CPA; Cyclopiazonic Acid
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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 |
| 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) |
DMSO : ~100 mg/mL (~297.28 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.43 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 25.0 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: ≥ 2.5 mg/mL (7.43 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.9728 mL | 14.8641 mL | 29.7283 mL | |
| 5 mM | 0.5946 mL | 2.9728 mL | 5.9457 mL | |
| 10 mM | 0.2973 mL | 1.4864 mL | 2.9728 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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