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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)
- Jervine targets the Hedgehog (Hh) signaling pathway, specifically inhibiting the Smoothened (Smo) receptor (IC50 for inhibiting Hh-dependent Gli-luciferase activity in NIH3T3 cells: ~10 μM) [1] - Jervine targets inflammatory mediators (including cyclooxygenase-2 (COX-2), nitric oxide synthase (iNOS)) and oxidative stress-related molecules (e.g., reactive oxygen species (ROS)-scavenging enzymes) [2] - Jervine targets cyclooxygenase-2 (COX-2) in human erythroleukemia cells [3] |
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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].
- For Hh signaling inhibition: In NIH3T3 cells stably expressing a Gli-luciferase reporter (Hh-responsive cells), Jervine (concentrations: 1–20 μM) dose-dependently inhibited Hh pathway activation induced by Sonic Hedgehog (Shh) conditioned medium. At 10 μM, it reduced Gli-luciferase activity by ~70% and downregulated Hh target genes (Gli1, Ptch1) mRNA expression (detected via RT-PCR). It also inhibited the proliferation of Hh-dependent basal cell carcinoma (BCC) cell lines (ASZ001) with an IC50 of ~12 μM (MTT assay) [1] - For anti-inflammatory and antioxidant activity: In LPS-stimulated RAW 264.7 macrophages, Jervine (concentrations: 5–25 μM) dose-dependently reduced nitric oxide (NO) production (inhibited by ~65% at 25 μM, Griess assay), downregulated iNOS and COX-2 protein expression (western blot), and decreased pro-inflammatory cytokines (TNF-α, IL-6) secretion (ELISA). It also increased intracellular glutathione peroxidase (GSH-Px) activity and superoxide dismutase (SOD) activity (by ~40% and ~35% at 25 μM, respectively) and reduced ROS levels (DCFH-DA fluorescence assay) [2] - For COX-2 regulation and cell viability: In human erythroleukemia K562 cells, Jervine (concentrations: 1–10 μM) dose-dependently upregulated COX-2 protein and mRNA expression (western blot, RT-PCR); at 10 μM, COX-2 mRNA was increased by ~3.5-fold. Unlike cyclopamine, Jervine (up to 10 μM) did not induce apoptosis (Annexin V-FITC/PI staining, flow cytometry) and had no significant effect on K562 cell viability (MTT assay, cell survival rate >90% at 10 μM) [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].
- For basal cell carcinoma (BCC)-like lesions: In a transgenic mouse model (K14-Cre;Ptch1flox/flox) that develops spontaneous BCC-like lesions, Jervine was administered via intraperitoneal injection at 20 mg/kg once every 2 days for 4 weeks. Compared to the vehicle control group, Jervine reduced the number of BCC-like lesions by ~50% and decreased lesion size (histological analysis). It also downregulated Hh target gene (Gli1, Ptch1) expression in lesion tissues (immunohistochemistry and RT-PCR) [1] - For anti-inflammatory activity: In a TPA-induced mouse ear edema model, Jervine was topically applied to the ear at doses of 0.1, 0.5, 1 mg/ear 30 minutes before TPA treatment. At 1 mg/ear, it reduced ear edema thickness by ~45% (caliper measurement) and decreased myeloperoxidase (MPO) activity (a marker of neutrophil infiltration) by ~55% (colorimetric assay). In a carrageenan-induced rat paw edema model, intraperitoneal injection of Jervine (5, 10, 20 mg/kg) 1 hour before carrageenan injection reduced paw edema volume by ~30%, ~45%, ~60% at 4 hours post-carrageenan, respectively [2] |
| Enzyme Assay |
- COX-2 activity assay: Purified recombinant human COX-2 enzyme was mixed with reaction buffer containing arachidonic acid (substrate) and Jervine (concentrations: 1–25 μM). The mixture was incubated at 37°C for 15 minutes, and the production of prostaglandin E2 (PGE2, a COX-2 product) was detected via ELISA. Jervine did not directly inhibit COX-2 enzyme activity but regulated its expression in cells. [2]
- Hh pathway Gli-luciferase assay: NIH3T3 cells transfected with Gli-luciferase reporter plasmid and Renilla luciferase plasmid (internal control) were pre-treated with Jervine (1–20 μM) for 1 hour, then stimulated with Shh-conditioned medium for 24 hours. Luciferase activity was measured using a dual-luciferase assay kit; the ratio of Gli-luciferase to Renilla luciferase activity was calculated to assess Hh pathway inhibition [1] |
| 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. - Hh-responsive cell assay (NIH3T3/Gli-luc): Cells were seeded in 96-well plates and cultured overnight. Jervine (1–20 μM) was added, followed by Shh-conditioned medium (1:1 dilution) after 1 hour. After 24 hours of incubation, cells were lysed, and luciferase activity was detected. For BCC cell proliferation assay (ASZ001), cells were seeded in 96-well plates, treated with Jervine (1–25 μM) for 72 hours, then MTT reagent was added and incubated for 4 hours; absorbance at 570 nm was measured to calculate cell viability [1] - Macrophage anti-inflammatory assay (RAW 264.7): Cells were seeded in 6-well plates, pre-treated with Jervine (5–25 μM) for 1 hour, then stimulated with LPS (1 μg/mL) for 24 hours. Culture supernatant was collected to detect NO (Griess assay) and cytokines (ELISA). Cells were lysed to extract protein for western blot (iNOS, COX-2) or measure GSH-Px/SOD activity (colorimetric kits) [2] - K562 cell COX-2 and apoptosis assay: Cells were seeded in 6-well plates, treated with Jervine (1–10 μM) for 24 hours. Cells were collected to extract RNA (RT-PCR for COX-2 mRNA) or protein (western blot for COX-2). For apoptosis detection, cells were treated with Jervine for 48 hours, stained with Annexin V-FITC/PI, and analyzed via flow cytometry [3] |
| 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. - BCC-like lesion mouse model: Transgenic K14-Cre;Ptch1flox/flox mice (8–10 weeks old) were randomly divided into vehicle and Jervine groups. Jervine was dissolved in DMSO (5%) + saline (95%) and administered via intraperitoneal injection at 20 mg/kg, once every 2 days for 4 weeks. Vehicle group received the same volume of DMSO/saline. Mice were euthanized after treatment; skin tissues with lesions were collected for histological and molecular analysis [1] - Mouse ear edema model: Male ICR mice (6–8 weeks old) were divided into groups (n=6). Jervine was dissolved in acetone (50%) + ethanol (50%) and topically applied to the right ear at 0.1, 0.5, 1 mg/ear. Vehicle group received acetone/ethanol. Thirty minutes later, TPA (10 μg/ear in acetone/ethanol) was applied to the right ear; left ear served as control. Ear thickness was measured 4 hours later; ears were collected to measure MPO activity [2] |
| ADME/Pharmacokinetics |
Metabolism / Metabolites
Applying 1-2 mg of cyclopamine directly to the embryonic shield of open-window chicken eggs can cause chick malformations. This indicates that maternal metabolic alterations to cyclopamine are not necessary. /PRC: Cyclopamine and jevinine both belong to the jevinatum group. / /Cyclopamine/ Acetic acid-1-(14)C, cholesterol-4-(14)C, and cholesterol-26-(14)C were incorporated into jevin and veratridine, resulting in a labeling pattern consistent with the following hypothesis: key intermediates derived from erythropoietin are converted into C-nor-D-high steroidal alkaloids (jevin and veratridine) via different pathways in veratrum. |
| Toxicity/Toxicokinetics |
Toxicity Summary
The biological activity of jevinine is mediated by its interaction with the seven-transmembrane protein Smoothened. Jevinine binds to and inhibits the activity of Smoothened, an important component of the Hedgehog signaling pathway. Inhibition of Smoothened prevents activation of GLI1 transcription and the transcription of Hedgehog target genes. (Wikipedia) The teratogenic effects of jevinine and cyclopamine are currently known to be due to their specific inhibition of vertebrate cell responses to growth factors secreted by the Hedgehog (Hh) family. (A15438) Compared to tongues in standard or solanine medium, cultures containing cyclopamine, jevinine, or blocking antibodies showed a doubling of the number of fungiform papillae on the dorsum of the tongue, with the distribution almost completely eliminating the interpapillary region. (A15439) - In vitro cytotoxicity: Jervinee (at concentrations up to 25 μM) showed no significant cytotoxicity to RAW 264.7 macrophages (MTT assay, cell viability >85%) [2] - In vivo acute toxicity: In ICR mice, a single intraperitoneal injection of Jervinee (50–200 mg/kg) did not result in death within 7 days; histological examination revealed no abnormal behavior (e.g., lethargy, ataxia) or organ damage (liver, kidney). The LD50 was >200 mg/kg (intraperitoneal injection) [2] - In vitro cell viability: Jervinee (1–10 μM) did not affect the viability of K562 cells (MTT assay, cell viability >90% at 10 μM) [3] |
| References |
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| Additional Infomation |
Jervine belongs to the piperidine class of compounds. It has been reported to exist in Veratrum dahuricum, Veratrum taliense, and other organisms with relevant data. Jervine is a steroidal alkaloid with the molecular formula C27H39NO3, derived from plants in the Veratrum genus. Similar to cyclopamine, also found in Veratrum plants, Jervine is a teratogen that causes birth defects when ingested by animals during specific periods of pregnancy. Mechanism of Action Cyclopamine (1) and Jervine (2) are potent teratogens that inhibit the Sonic hedgehog (Shh) signaling pathway during gastrulation in embryonic development, leading to cyclopsy and holohemorrhagic forebrain. Teratogenicity tests have been conducted on various Veratrum alkaloids in pregnant sheep. The malformations produced by compounds Jervine, cyclopamine, and cyclopamine are similar to those in natural cases. These three teratogenic compounds are closely related steroidal furanylpiperidine compounds, but cyclopamine has significant natural teratogenicity due to its concentration in plants. A compound closely related to this compound, lacking a furan ring, does not cause unilateral ecchymosis in sheep, suggesting that the intact furan ring is essential for its activity and may confer a necessary configuration to the molecule.
- Jevin is a steroidal alkaloid isolated from the rhizome of Veratrum album [2] - As an Hh pathway inhibitor, Jevin has shown potential for treating Hh-driven cancers (e.g., basal cell carcinoma) by blocking Smo-mediated signal transduction [1] - Unlike cyclopamine (a structure-related steroidal alkaloid), Jevin upregulates COX-2 expression in K562 cells but lacks pro-apoptotic activity, suggesting that its structural differences lead to…functional divergence [3] |
| Molecular Formula |
C27H39NO3
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|---|---|
| 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
|
| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
0
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| Heavy Atom Count |
31
|
| Complexity |
876
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| Defined Atom Stereocenter Count |
10
|
| 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
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| 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
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| 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
|
| 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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