| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
| Targets |
No direct pharmacological target; cis-Vitamin K1 is an inactive isomer. The trans isomer of vitamin K1 targets vitamin K-dependent carboxylase (VKOR and gamma-glutamyl carboxylase) and is an essential cofactor for the post-translational activation of blood coagulation factors (factors II, VII, IX, X) and bone proteins (osteocalcin, matrix Gla protein). The cis-isomer, however, is not biologically active due to its altered three-dimensional structure preventing proper interaction with the vitamin K epoxide reductase (VKOR) or the carboxylase enzyme complex.
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| ln Vitro |
Cis-Vitamin K1 shows no significant biological activity in vitro. The trans isomer of vitamin K1 (phylloquinone) is essential for the gamma-carboxylation of glutamate residues in vitamin K-dependent proteins (VKDPs), including coagulation factors (II, VII, IX, X) and bone proteins (osteocalcin, matrix Gla-protein). In vitro, trans-vitamin K1 (1-100 uM) activates VKOR, regenerates vitamin K hydroquinone, and supports carboxylase activity. However, cis-vitamin K1 does not support these reactions. In cell-based assays (e.g., HepG2 hepatocytes or osteoblasts), trans-vitamin K1 treatment (1-50 uM, 24-48 h) increases carboxylated osteocalcin and active coagulation factors; cis-vitamin K1 has no effect. In some enzyme assays, cis-vitamin K1 may competitively inhibit VKOR, but its affinity is much lower than trans-vitamin K1. Consequently, cis-vitamin K1 is considered biologically inactive and is primarily used as an internal standard or negative control in research.
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| ln Vivo |
No direct in vivo activity. The trans isomer of vitamin K1 is essential for blood coagulation and bone metabolism. trans-Vitamin K1 is administered as phytonadione to treat vitamin K deficiency and warfarin overdose. In animal models, trans-vitamin K1 (1-10 mg/kg, PO, SC, or IV) reverses warfarin-induced anticoagulation within 2-6 h by increasing the levels of carboxylated (active) clotting factors. trans-Vitamin K1 also supports bone health by promoting osteocalcin carboxylation and reducing bone fracture risk. In contrast, cis-vitamin K1 is not biologically active and does not support coagulation or bone metabolism. In pharmacokinetic studies, cis-vitamin K1 can be detected as a minor endogenous metabolite of trans-vitamin K1, likely formed by isomerization in vivo. cis-Vitamin K1 is not used therapeutically and has no known physiological function.
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| Enzyme Assay |
No specific binding assay. For use as an internal standard for the quantification of vitamin K1 (trans form) by LC-MS/MS: (1) Prepare a stock solution of cis-Vitamin K1 in methanol or ethanol at 1 mg/mL. (2) Prepare calibration standards by spiking known concentrations of trans-vitamin K1 (analyte) with a fixed concentration of cis-Vitamin K1 (internal standard, 50-500 ng/mL) into blank plasma, serum, or tissue homogenates. (3) For extraction: add 200-500 uL of internal standard solution in isopropanol or methanol to 100-200 uL of sample. (4) Add 1-2 mL of hexane (or hexane:isopropanol 95:5), vortex vigorously for 5 min, centrifuge at 3000 rpm for 10 min. (5) Transfer organic layer to a clean tube, evaporate under nitrogen. (6) Reconstitute in 100-200 uL of mobile phase (e.g., methanol:water 98:2 with 2 mM ammonium acetate). (7) Separate on a C18 reverse-phase column (2.1 × 50 mm, 1.7 um) at 40degC with isocratic elution (98% methanol, 2% 2 mM ammonium acetate). (8) Detect by ESI-MS/MS in positive ion mode. MRM transitions: trans- and cis-Vitamin K1: m/z 451 → 187 (or 451 → 199). Both isomers have the same m/z transitions but slightly different retention times (trans elutes slightly earlier or later depending on column chemistry). (9) Quantify trans-vitamin K1 using the analyte/internal standard peak area ratio.
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| Cell Assay |
(1) For cellular assays: seed HepG2 cells (5 × 10⁵ cells/well) in 6-well plates in DMEM with 10% FBS overnight. (2) To study vitamin K1 metabolism, treat cells with trans-vitamin K1 (1-10 uM) for 0-24 h. (3) Extract cellular lipids using hexane/isopropanol (3:2), evaporate, and reconstitute in mobile phase. (4) Analyze cis-vitamin K1 and trans-vitamin K1 by LC-MS/MS as described in field 5. (5) Detect the conversion of trans-vitamin K1 to cis-vitamin K1 in cells, which may occur as a minor metabolism pathway. (6) For negative control, treat cells with cis-vitamin K1 (1-10 uM) and demonstrate no effect on vitamin K-dependent carboxylation (e.g., measure Factor X activity or osteocalcin carboxylation by ELISA). (7) For cell viability: treat cells with cis- or trans-vitamin K1 (1-100 uM) for 24-72 h, perform MTT assay to ensure no cytotoxicity.
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| Animal Protocol |
(1) For in vivo metabolism studies: use 6-8 week old male Sprague-Dawley rats (200-250 g) or C57BL/6 mice (20-25 g). (2) Administer trans-vitamin K1 orally (1-10 mg/kg) or intravenously (0.1-1 mg/kg). (3) Collect blood at predetermined time points (0, 0.5, 1, 2, 4, 8, 12, 24 h) from tail vein or by cardiac puncture. (4) Collect liver tissue at endpoint (4-24 h). (5) Extract plasma and liver tissue with hexane/isopropanol (3:2) as described, add cis-Vitamin K1 as an internal standard for quantification. (6) Analyze trans-vitamin K1 concentrations by LC-MS/MS using the cis isomer as the internal standard. (7) Determine PK parameters of trans-vitamin K1: Cmax, Tmax, t1/2, AUC, clearance, volume of distribution. (8) Detect the formation of cis-vitamin K1 as a minor metabolite of trans-vitamin K1 in plasma and liver. (9) For negative control group, administer cis-vitamin K1 (1-10 mg/kg, PO or IV) and assess its effect on coagulation parameters (prothrombin time, PT) and vitamin K-dependent carboxylation. cis-Vitamin K1 should show no effect on PT or carboxylation. (10) For warfarin reversal studies: pre-treat rats with warfarin (2 mg/kg, PO) for 24-48 h to prolong PT (INR > 3). Then administer trans-vitamin K1 (1-10 mg/kg, PO or SC) or cis-vitamin K1 (same dose). Measure PT at 2, 6, 12, 24 h post-vitamin K1. cis-Vitamin K1 should not reverse warfarin-induced anticoagulation.
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| ADME/Pharmacokinetics |
Standard formulation for cis-Vitamin K1 as an internal standard: prepare a stock solution in methanol, ethanol, or hexane at 1 mg/mL. Store at -20degC protected from light. For LC-MS analysis, dilute stock solution in methanol to working concentration (0.5-10 ug/mL). Storage: store powder at -20degC for 3 years; in solution at -80degC for 6 months, -20degC for 1 month. Protect from light at all times as vitamin K1 isomers are light-sensitive. For in vivo studies: for oral gavage, dissolve in corn oil or sesame oil at 1-10 mg/mL (sonicate if needed). For IV/SC injection, formulate in 10% ethanol, 40% PEG300, 5% Tween-80, 45% saline or in liposomal carriers. cis-Vitamin K1 is chemically stable under neutral and anhydrous conditions but may isomerize to trans-vitamin K1 under prolonged exposure to light or at high temperatures. Solubility: very low in water (<0.01 mg/mL), soluble in organic solvents (ethanol, methanol, acetone, hexane, corn oil). PK of trans-Vitamin K1 in humans: after oral administration, absorption is dependent on fat intake; t1/2 ~ 10-40 h; oral bioavailability ~ 10-80% depending on formulation. In rats, oral bioavailability ~ 20-50%, t1/2 ~ 3-6 h. cis-Vitamin K1 is not expected to have significant absorption differences.
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| Toxicity/Toxicokinetics |
cis-Vitamin K1 is considered non-toxic as it is a naturally occurring isomer of vitamin K1 with minimal biological activity. The trans isomer of vitamin K1 is well-tolerated with a high safety margin; LD50 > 5000 mg/kg (PO) in rodents. Adverse effects from vitamin K1 are rare and include hypersensitivity reactions (mainly after IV administration), flushing, and nausea. cis-Vitamin K1 is not administered therapeutically. In vitro: CCK-8 assay on HepG2 cells with cis-vitamin K1 (1-100 uM, 48 h) shows no cytotoxicity (IC50 > 100 uM). In vivo toxicity: acute oral LD50 in rats > 5000 mg/kg. No teratogenic, mutagenic, or carcinogenic effects have been reported. The compound is for research use only, not for human therapeutic use. As with all research chemicals, wear gloves, lab coat, and eye protection when handling. Avoid skin contact as vitamin K1 is a fat-soluble vitamin that may cause local irritation.
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| References | |
| Additional Infomation |
cis-Vitamin K1 is the cis-isomer of phylloquinone (vitamin K1), a naturally occurring form of vitamin K found in green leafy vegetables. The trans-isomer is the biologically active form that serves as an essential cofactor for the gamma-carboxylation of vitamin K-dependent proteins (VKDPs), including blood coagulation factors (II, VII, IX, X) and bone proteins (osteocalcin, matrix Gla protein). The cis-isomer is considered inactive due to its altered three-dimensional conformation, which prevents proper binding to vitamin K epoxide reductase (VKOR) and the gamma-glutamyl carboxylase enzyme complex. cis-Vitamin K1 can be formed from trans-vitamin K1 by photoisomerization (exposure to light). It is used in research primarily as an internal standard for LC-MS/MS quantification of vitamin K1 (trans form) in biological samples and as a negative control in studies of vitamin K biology. cis-Vitamin K1 is not FDA-approved and is strictly for research use only. It is not intended for therapeutic or clinical applications. Storage should be at -20degC in dark amber vials to prevent light-induced isomerization.
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| Molecular Formula |
C31H46O2
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|---|---|
| Molecular Weight |
450.70
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| Exact Mass |
450.35
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| CAS # |
16033-41-3
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| Related CAS # |
Vitamin K1;84-80-0;Vitamin K1-d7;1233937-39-7;cis-Vitamin K1-d7;Vitamin K1-d4;5172-18-9
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| PubChem CID |
9846607
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
9.157
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
14
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| Heavy Atom Count |
33
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| Complexity |
696
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| Defined Atom Stereocenter Count |
2
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| SMILES |
CC1=C(C(=O)C2=CC=CC=C2C1=O)C/C=C(/C)\CCC[C@H](C)CCC[C@H](C)CCCC(C)C
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| InChi Key |
MBWXNTAXLNYFJB-ODDKJFTJSA-N
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| InChi Code |
InChI=1S/C31H46O2/c1-22(2)12-9-13-23(3)14-10-15-24(4)16-11-17-25(5)20-21-27-26(6)30(32)28-18-7-8-19-29(28)31(27)33/h7-8,18-20,22-24H,9-17,21H2,1-6H3/b25-20-/t23-,24-/m1/s1
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| Chemical Name |
2-methyl-3-[(Z,7R,11R)-3,7,11,15-tetramethylhexadec-2-enyl]naphthalene-1,4-dione
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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 | 2.2188 mL | 11.0939 mL | 22.1877 mL | |
| 5 mM | 0.4438 mL | 2.2188 mL | 4.4375 mL | |
| 10 mM | 0.2219 mL | 1.1094 mL | 2.2188 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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