| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
Tigilanol tiglate targets the protein kinase C (PKC)/C1 domain, activating the PKC signaling cascade. This activation leads to mitochondrial and endoplasmic reticulum dysfunction, ATP depletion, caspase activation, and gasdermin E cleavage, ultimately causing terminal necrosis and immunogenic cell death. It induces an acute inflammatory response, hypoxia, and activates innate immune cells including neutrophils.
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| ln Vitro |
Tigilanol tiglate promotes mitochondrial/endoplasmic reticulum dysfunction, leading to ATP depletion, caspase activation, and gasdermin E cleavage. It induces immunogenic cell death, enhancing the response to immune checkpoint blockade in both target tumors and non-injected tumors, resulting in tumor regression. It is a PKC/C1 domain activator with potent anti-tumor activity.
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| ln Vivo |
Upon intratumoral administration, Tigilanol tiglate disrupts mitochondrial functioning and induces mitochondrial swelling, leading to oncolysis of tumor cells in direct contact with the agent. It activates the PKC signaling cascade, leading to an acute inflammatory response, hypoxia, and activation of innate immune cells. It induces tumor regression in animal models.
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| Enzyme Assay |
In vitro enzyme assays for Tigilanol tiglate are not standard, as its mechanism involves PKC activation rather than direct enzyme inhibition. However, its ability to activate PKC can be measured using kinase activity assays, where PKC is incubated with the compound and a substrate, and phosphorylation is quantified. Its effects on mitochondrial function can be assessed by measuring ATP levels and mitochondrial membrane potential.
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| Cell Assay |
In vitro cellular assays for Tigilanol tiglate involve treating cancer cell lines with the compound and measuring cell viability, apoptosis, and immunogenic cell death markers. Its effects on mitochondrial and ER function are assessed by measuring ATP levels, caspase activation, and gasdermin E cleavage. Its ability to induce immune cell activation can be studied in co-culture systems.
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| Animal Protocol |
In vivo animal models for Tigilanol tiglate include xenograft models of head and neck squamous cell carcinoma, soft tissue sarcoma, and other solid tumors. Intratumoral administration is used, and tumor regression is measured. Its effects on the immune system are assessed by measuring immune cell infiltration and activation in the tumor microenvironment.
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| ADME/Pharmacokinetics |
Tigilanol tiglate is administered intratumorally for local treatment of skin malignancies. Its pharmacokinetic profile is characterized by local retention and systemic clearance. It is metabolized in the liver, and its metabolites are excreted in urine and feces. Its half-life and bioavailability are consistent with its local administration route.
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| Toxicity/Toxicokinetics |
Tigilanol tiglate is generally well-tolerated at therapeutic doses when administered intratumorally. Local side effects may include injection site reactions, pain, and inflammation. Systemic toxicity is limited due to its local administration. Its safety has been evaluated in preclinical studies and clinical trials.
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| References |
: Boyle GM, D'Souza MM, Pierce CJ, Adams RA, Cantor AS, Johns JP, Maslovskaya L, Gordon VA, Reddell PW, Parsons PG. Intra-lesional injection of the novel PKC activator EBC-46 rapidly ablates tumors in mouse models. PLoS One. 2014 Oct 1;9(10):e108887. doi: 10.1371/journal.pone.0108887. eCollection 2014. PubMed PMID: 25272271; PubMed Central PMCID: PMC4182759.
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| Additional Infomation |
Tigilanol tiglate is a diterpenoid natural product isolated from the seeds of the Australian redwood tree (Fontainea picrosperma). It has been approved as a veterinary drug for the treatment of non-metastatic and unresectable canine mast cell tumors. It possesses antitumor activity and is a plant metabolite and protein kinase C agonist. It is a diterpenoid compound, phorbol ester, diester, and organic heteropentane compound. Tigilanol tiglate is a short-chain diterpenoid ester isolated from the seeds of the Australian redwood tree with potential antitumor activity. Upon intratumoral injection, tigilanol tiglate disrupts mitochondrial function and induces mitochondrial swelling, leading to the lysis of tumor cells in direct contact with the drug. Furthermore, tigilanol tiglate activates the protein kinase C (PKC) signaling cascade, triggering an acute inflammatory response. This leads to hypoxia and activates innate immune cells, including neutrophils and macrophages, further killing tumor cells. Activation of the PKC β-II subtype (PKC β II) also increases tumor vascular permeability, leading to tumor vascular destruction.
Drug Indications For the treatment of unresectable, non-metastatic (WHO staging) subcutaneous mast cell tumors of the elbow or tarsal joint and distal parts of the dog, as well as unresectable, non-metastatic cutaneous mast cell tumors. Tigilanol tiglate is a natural product and PKC/C1 domain activator with potent antitumor activity. It is administered intratumorally for skin malignancies. It induces mitochondrial dysfunction, ATP depletion, caspase activation, and immunogenic cell death. It has been studied for head and neck squamous cell carcinoma and soft tissue sarcoma. |
| Molecular Formula |
C30H42O10
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|---|---|
| Molecular Weight |
562.66
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| Exact Mass |
562.277
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| CAS # |
943001-56-7
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| Related CAS # |
943001-56-7
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| PubChem CID |
92135637
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| Appearance |
White to off-white solid powder
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| Density |
1.35±0.1 g/cm3(Predicted)
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| Boiling Point |
682.1±55.0 °C(Predicted)
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| LogP |
2.1
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
40
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| Complexity |
1220
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| Defined Atom Stereocenter Count |
12
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| SMILES |
CC[C@H](C)C(=O)O[C@@]12[C@@H](C1(C)C)[C@@H]3[C@H]4[C@](O4)([C@H]([C@]5([C@H]([C@]3([C@@H]([C@H]2OC(=O)/C(=C/C)/C)C)O)C=C(C5=O)C)O)O)CO
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| InChi Key |
YLQZMOUMDYVSQR-RMNSOQACSA-N
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| InChi Code |
InChI=1S/C30H42O10/c1-9-13(3)23(33)38-21-16(6)28(36)17-11-15(5)20(32)29(17,37)25(35)27(12-31)22(39-27)18(28)19-26(7,8)30(19,21)40-24(34)14(4)10-2/h9,11,14,16-19,21-22,25,31,35-37H,10,12H2,1-8H3/b13-9+/t14?,16-,17?,18?,19?,21-,22+,25-,27+,28+,29-,30-/m1/s1
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| Chemical Name |
(1cS,2aR,3S,3aS,6bR,7R,8R,8aS)-3,3a,6b-trihydroxy-2a-(hydroxymethyl)-1,1,5,7-tetramethyl-8a-((2-methylbutanoyl)oxy)-4-oxo-1a,1b,1c,2a,3,3a,4,6a,6b,7,8,8a-dodecahydro-1H-cyclopropa[5',6']benzo[1',2'
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| Synonyms |
Tigilanol tiglate EBC-46 EBC46 EBC 46
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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) |
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
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|---|---|
| Solubility (In Vivo) |
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 Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *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)] Oral Formulations
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 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7773 mL | 8.8864 mL | 17.7727 mL | |
| 5 mM | 0.3555 mL | 1.7773 mL | 3.5545 mL | |
| 10 mM | 0.1777 mL | 0.8886 mL | 1.7773 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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