Details
| Stereochemistry | ACHIRAL |
| Molecular Formula | C31H40O2 |
| Molecular Weight | 444.6481 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 3 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
CC(C)=CCC\C(C)=C\CC\C(C)=C\CC\C(C)=C\CC1=C(C)C(=O)C2=CC=CC=C2C1=O
InChI
InChIKey=DKHGMERMDICWDU-GHDNBGIDSA-N
InChI=1S/C31H40O2/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/h7-8,12,14,16,18-20H,9-11,13,15,17,21H2,1-6H3/b23-14+,24-16+,25-20+
| Molecular Formula | C31H40O2 |
| Molecular Weight | 444.6481 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 3 |
| Optical Activity | NONE |
DescriptionCurator's Comment: description was created based on several sources, including
http://www.ncbi.nlm.nih.gov/pubmed/8511981
Curator's Comment: description was created based on several sources, including
http://www.ncbi.nlm.nih.gov/pubmed/8511981
Menatetrenone (INN), also known as MK4, is a vitamin K compound used as a hemostatic agent, and also as adjunctive therapy for the pain of osteoporosis. MK4 is marketed for the osteoporosis indication in Japan by Eisai Co., under the trade name Glakay. Has several mechanism of actions: (1) Acceleration of osteogenesis. In human osteoblast cultures, calcification was accelerated by administration of menatetrenone at a concentration of 2.25 × 10-6 mol/L alone or when it was coadministered with 1,25(OH)2D3. The osteocalcin content in the cell layers was increased by coadministration with 1,25(OH)2D3. 2. Inhibition of bone resorption. In organ cultures of mouse calvaria, at concentrations of 3 × 10-6 to 3 × 10-5 mol/L, menatetrenone inhibited bone resorption induced by IL-1α, PGE2, PTH and 1,25(OH)2D3. In mouse bone marrow cell cultures, at concentrations of 3 × 10-6 to 1 × 10-5 mol/L, menatetrenone inhibited the induction of osteoclast release by 1,25(OH)2D3. 3. Effect on serum level of osteocalcin. Menatetrenone was administered to patients with osteoporosis at a dose of 45 mg/day for 2 years. Menatetrenone increased the serum level of osteocalcin and decreased the serum level of Glu-osteocalcin.
Originator
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Target ID: Acceleration of osteogenesis |
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Target ID: GO:0045453 |
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Target ID: serum level of osteocalcin |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Primary | Glakay Approved UseImprovement of decrease in bone mass and relief of pain in patients with osteoporosis Launch Date2004 |
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
139.7 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8877895/ |
15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered: |
MENATETRENONE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED |
|
409.4 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8877895/ |
15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered: |
MENATETRENONE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: HIGH-FAT |
|
133.4 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8877895/ |
15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered: |
MENATETRENONE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: LOW-FAT |
AUC
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
485.2 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8877895/ |
15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered: |
MENATETRENONE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED |
|
1024.4 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8877895/ |
15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered: |
MENATETRENONE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: HIGH-FAT |
|
370.6 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8877895/ |
15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered: |
MENATETRENONE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: LOW-FAT |
Doses
| Dose | Population | Adverse events |
|---|---|---|
90 mg 1 times / day multiple, oral Highest studied dose Dose: 90 mg, 1 times / day Route: oral Route: multiple Dose: 90 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sex: M+F Food Status: UNKNOWN Sources: |
Other AEs: Glutamic-oxaloacetic transaminase increased, Alkaline phosphatase... Other AEs: Glutamic-oxaloacetic transaminase increased (1 pt) Sources: Alkaline phosphatase (1 pt) Glutamic-pyruvic transaminase increased (1 pt) Gamma glutamyl transpeptidase increased (1 pt) |
AEs
| AE | Significance | Dose | Population |
|---|---|---|---|
| Alkaline phosphatase | 1 pt | 90 mg 1 times / day multiple, oral Highest studied dose Dose: 90 mg, 1 times / day Route: oral Route: multiple Dose: 90 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sex: M+F Food Status: UNKNOWN Sources: |
| Gamma glutamyl transpeptidase increased | 1 pt | 90 mg 1 times / day multiple, oral Highest studied dose Dose: 90 mg, 1 times / day Route: oral Route: multiple Dose: 90 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sex: M+F Food Status: UNKNOWN Sources: |
| Glutamic-oxaloacetic transaminase increased | 1 pt | 90 mg 1 times / day multiple, oral Highest studied dose Dose: 90 mg, 1 times / day Route: oral Route: multiple Dose: 90 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sex: M+F Food Status: UNKNOWN Sources: |
| Glutamic-pyruvic transaminase increased | 1 pt | 90 mg 1 times / day multiple, oral Highest studied dose Dose: 90 mg, 1 times / day Route: oral Route: multiple Dose: 90 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sex: M+F Food Status: UNKNOWN Sources: |
PubMed
| Title | Date | PubMed |
|---|---|---|
| Synthesis of novel vitamin K2 analogues with modification at the ω-terminal position and their biological evaluation as potent steroid and xenobiotic receptor (SXR) agonists. | 2011-06-23 |
|
| Identification of UBIAD1 as a novel human menaquinone-4 biosynthetic enzyme. | 2010-11-04 |
|
| Prevention of hepatocarcinogenesis with phosphatidylcholine and menaquinone-4: in vitro and in vivo experiments. | 2007-07 |
|
| Quinones as antimycobacterial agents. | 2004-09-15 |
|
| Vitamin K(2) inhibits adipogenesis, osteoclastogenesis, and ODF/RANK ligand expression in murine bone marrow cell cultures. | 2000-12 |
Sample Use Guides
The usual adult dosage for oral use is 45 mg of menatetrenone daily in three divided doses after meals.
Route of Administration:
Oral
In Vitro Use Guide
Sources: http://www.ncbi.nlm.nih.gov/pubmed/8511981
Menatetrenone (3 x 10(-6)-3 x 10(-5) M) inhibited the bone resorption induced by IL-1 alpha (2 U/ml), PGE2 (10(-7) M), PTH (3 x 10(-7) M), and 1,25-(OH)2D3 (3 x 10(-10) M) in a dose-dependent manner. Menatetrenone also inhibited the PGE2 production stimulated by IL-1 alpha. These results indicate that menatetrenone may inhibit bone resorption through at least two different mechanisms; one possibly is an inhibitory effect on prostaglandin production.
| Substance Class |
Chemical
Created
by
admin
on
Edited
Mon Mar 31 18:26:34 GMT 2025
by
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| Record UNII |
27Y876D139
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Validated (UNII)
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| Classification Tree | Code System | Code | ||
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NCI_THESAURUS |
C26017
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FDA ORPHAN DRUG |
319110
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FDA ORPHAN DRUG |
348111
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FDA ORPHAN DRUG |
319210
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FDA ORPHAN DRUG |
319910
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FDA ORPHAN DRUG |
320810
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27Y876D139
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78277
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MENATETRENONE
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C52194
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m7171
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16374
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100000081471
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29495
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SUB08736MIG
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DTXSID6048969
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27Y876D139
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C030814
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