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Purity: ≥98%
Jervine (11-Ketocyclopamine) is a naturally occurring steroidal alkaloid found in rhizomes of Veratrum nigrum and has anti-inflammatory and antioxidant activity. It cab cause cyclopia by blocking sonic hedgehog(Shh) signaling and acting as an inhibitor of Smo.
| Targets |
Hedgehog (IC50 = 500-700 nM)
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|---|---|
| ln Vitro |
Jervine suppresses the phosphorylation of Akt at 40 μM for 6, 12, and 24 hours [3]. Jervine (40 μM; 2 hours) causes apoptosis, lowers COX-2 overexpression, and inhibits NF-jB activation [3].
|
| ln Vivo |
When applied topically, jervine (oral; 50–400 mg/kg) reduces inflammation by 50.4–73.5% in paw edema caused by carrageenan [2].
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| Cell Assay |
Western Blot Analysis[1]
Cell Types: HEL and TF1a Cell Tested Concentrations: 40 μM Incubation Duration: 6, 12 and 24 hrs (hours) Experimental Results: Akt phosphorylation is inhibited. |
| Animal Protocol |
Animal/Disease Models: Male Sprague Dawley rat (180-200 g) [2]
Doses: 50, 100, 200 and 400 mg/kg Route of Administration: Oral Experimental Results: 50.4-73.5% response to carrageenan-induced paw edema anti-inflammatory effect. |
| ADME/Pharmacokinetics |
Metabolism / Metabolites
Malformations in hatched chicks were produced by direct application of 1-2 mg of cyclopamine to the embryonic shield of windowed chicken eggs. This showed that maternal metabolic alteration of cyclopamine was not necessary. /PRC: Cyclopamine is a member of the jerveratum group as is jervine/. /CYCLOPAMINE/ INCORPORATION OF ACETATE-1-(14)C, CHOLESTEROL-4-(14)C, & OF CHOLESTEROL-26-(14)C INTO JERVINE & VERATRAMINE GAVE A LABELING PATTERN CONSISTENT WITH THE HYPOTHESIS THAT A KEY INTERMEDIATE DERIVED FROM EPIRUBIJERVINE WAS CONVERTED INTO THE C-NOR-D-HOMOSTEROIDAL ALKALOIDS (JERVINE & VERATRAMINE) BY SEPARATE PATHWAYS IN VERATRUM GRANDIFLORUM. |
| Toxicity/Toxicokinetics |
Toxicity Summary
Jervine's biological activity is mediated via its interaction with the 7 pass trans membrane protein smoothened. Jervine binds with and inhibits smoothened, which is an integral part of the hedgehog signaling pathways. With smoothened inhibited, the GLI1 transcription cannot be activated and hedgehog target genes cannot be transcribed. (Wikipedia) It is now known that the teratogenic effects of jervine and cyclopamine are due to their specific inhibition of vertebrate cellular responses to the Hedgehog (Hh) family of secreted growth factors. (A15438) In cultures with cyclopamine, jervine, or blocking antibody, fungiform papilla numbers doubled on the dorsal tongue with a distribution that essentially eliminated inter-papilla regions, compared with tongues in standard medium or solanidine. (A15439) |
| References |
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| Additional Infomation |
Jervine is a member of piperidines.
Jervine has been reported in Veratrum dahuricum, Veratrum taliense, and other organisms with data available. Jervine is a steroidal alkaloid with molecular formula C27H39NO3 which is derived from the Veratrum plant genus. Similar to cyclopamine, which also occurs in the Veratrum genus, it is a teratogen implicated in birth defects when consumed by animals during a certain period of their gestation. Mechanism of Action Cyclopamine (1) and jervine (2) are potent teratogens that inhibit Sonic hedgehog (Shh) signaling during gastrulation-stage embryonic development, producing cyclopia and holoprosencephaly. A NUMBER OF VERATRUM ALKALOIDS WERE TESTED IN PREGNANT SHEEP FOR TERATOGENICITY. THE COMPOUNDS JERVINE, CYCLOPAMINE...AND CYCLOPOSINE...PRODUCED DEFORMITIES SIMILAR TO NATURAL CASES. THE 3 TERATOGENIC COMPOUNDS ARE CLOSELY RELATED STEROIDAL FURANOPIPERIDINES, BUT CYCLOPAMINE IS THE TERATOGEN OF NATURAL IMPORTANCE BECAUSE OF PLANT CONCN. CLOSELY RELATED COMPD DEVOID OF THE FURAN RING DID NOT PRODUCE CYCLOPIA IN SHEEP, SUGGESTING THAT AN INTACT FURAN RING WAS REQUIRED FOR ACTIVITY, PERHAPS CONFERRING SOME ESSENTIAL CONFIGURATION ON THE MOLECULE. |
| Molecular Formula |
C27H39NO3
|
|---|---|
| Molecular Weight |
425.6035
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| Exact Mass |
425.292
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| CAS # |
469-59-0
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| PubChem CID |
10098
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| Appearance |
NEEDLES FROM METHANOL + WATER
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
592.0±50.0 °C at 760 mmHg
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| Melting Point |
242- 244ºC
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| Flash Point |
311.8±30.1 °C
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| Vapour Pressure |
0.0±3.8 mmHg at 25°C
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| Index of Refraction |
1.591
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| LogP |
3.46
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
0
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| Heavy Atom Count |
31
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| Complexity |
876
|
| Defined Atom Stereocenter Count |
10
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| SMILES |
O1[C@]2([H])C([H])([H])[C@]([H])(C([H])([H])[H])C([H])([H])N([H])[C@@]2([H])[C@@]([H])(C([H])([H])[H])[C@@]21C(C([H])([H])[H])=C1C([C@]3([H])[C@@]4(C([H])([H])[H])C([H])([H])C([H])([H])[C@@]([H])(C([H])([H])C4=C([H])C([H])([H])[C@@]3([H])[C@]1([H])C([H])([H])C2([H])[H])O[H])=O
|
| InChi Key |
CLEXYFLHGFJONT-DNMILWOZSA-N
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| InChi Code |
InChI=1S/C27H39NO3/c1-14-11-21-24(28-13-14)16(3)27(31-21)10-8-19-20-6-5-17-12-18(29)7-9-26(17,4)23(20)25(30)22(19)15(27)2/h5,14,16,18-21,23-24,28-29H,6-13H2,1-4H3/t14-,16+,18-,19-,20-,21+,23+,24-,26-,27-/m0/s1
|
| Chemical Name |
(3S,3'R,3'aS,6'S,6aS,6bS,7'aR,9R,11aS,11bR)-3-hydroxy-3',6',10,11b-tetramethylspiro[1,2,3,4,6,6a,6b,7,8,11a-decahydrobenzo[a]fluorene-9,2'-3a,4,5,6,7,7a-hexahydro-3H-furo[3,2-b]pyridine]-11-one
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| Synonyms |
JERVINE; 469-59-0; Iervin; 11-Ketocyclopamine; Jerwiny [Polish]; CHEBI:6088; CHEMBL186779; (3S,3'R,3'aS,6'S,6aS,6bS,7'aR,9R,11aS,11bR)-3-hydroxy-3',6',10,11b-tetramethylspiro[1,2,3,4,6,6a,6b,7,8,11a-decahydrobenzo[a]fluorene-9,2'-3a,4,5,6,7,7a-hexahydro-3H-furo[3,2-b]pyridine]-11-one;
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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 : ~1 mg/mL (~2.35 mM)
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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 | 2.3496 mL | 11.7481 mL | 23.4962 mL | |
| 5 mM | 0.4699 mL | 2.3496 mL | 4.6992 mL | |
| 10 mM | 0.2350 mL | 1.1748 mL | 2.3496 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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