Details
| Stereochemistry | ABSOLUTE |
| Molecular Formula | C27H38O3 |
| Molecular Weight | 410.5888 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 6 / 6 |
| E/Z Centers | 3 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
C[C@H](\C=C\C(=O)C1CC1)[C@H]2CC[C@@H]3[C@]2(C)CCC\C3=C/C=C4/C[C@@H](O)C[C@H](O)C4=C
InChI
InChIKey=KKDBQSPKXAUHPH-NRCQPIEOSA-N
InChI=1S/C27H38O3/c1-17(6-13-25(29)20-8-9-20)23-11-12-24-19(5-4-14-27(23,24)3)7-10-21-15-22(28)16-26(30)18(21)2/h6-7,10,13,17,20,22-24,26,28,30H,2,4-5,8-9,11-12,14-16H2,1,3H3/b13-6+,19-7+,21-10-/t17-,22-,23-,24+,26+,27-/m1/s1
| Molecular Formula | C27H38O3 |
| Molecular Weight | 410.5888 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ABSOLUTE |
| Additional Stereochemistry | No |
| Defined Stereocenters | 6 / 6 |
| E/Z Centers | 3 |
| Optical Activity | UNSPECIFIED |
DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/8106449Curator's Comment: Description was created using several sources including:
http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/020273s013,020554s012lbl.pdf|https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3982071/
Sources: https://www.ncbi.nlm.nih.gov/pubmed/8106449
Curator's Comment: Description was created using several sources including:
http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/020273s013,020554s012lbl.pdf|https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3982071/
MC-1046 (Impurity A of Calcipotriol) is the C22-23-unsaturated 24-ketone, an active metabolite of the synthetic vitamin D analog calcipotriol (calcipotriene, MC 903). Calcipotriene is a ligand of VDR-like receptors approved for topical dermatological use indicated for the treatment of plaque psoriasis. It is approved by FDA in United States under the trade name Dovonex. Calcipotriol displays minimal effects on calcium homeostasis, and regulates cell differentiation, and proliferation exhibiting antiproliferative activity against human HL-60, HL60/MX2, MCF-7, T47D, SCC-25 and mouse WEHI-3 cancer cell lines. Calcipotriol is an effective anti-proliferative agent when applied topically at high concentrations but it is relatively “noncalcemic” in vivo (administered perorally, intravenously or intraperitoneally) because it can be metabolized by a variety of cells to metabolites with reduced biological activity as was demonstrated in vitro using rat and human cell lines from liver, bone, kidney, and keratinocytes. MC1046 is the initial calcipotriol metabolite which concentration reaches a steady state after 4 h of incubation with cells in vitro whereas the concentration of another major MC 903 metabolite MC1080, C22-23-saturated 24-ketone, continues to increase linearly over the time period tested (20 h). These two metabolites have also been detected in vivo in serum from rats and pigs dosed with MC903. MC1046 has the ability to stimulate e VDRE-mediated human growth hormone production in COS-1 cells co-transfected with pSG5hVDR1/3 and (CT4)4TKGH vectors and also binds to VDR although with lower (1/133) binding affinity compared to calcipotriol.
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Target ID: CHEMBL1977 |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Primary | Dovonex Approved UseDovonex (calcipotriene, MC-1046 is an active metabolite of calcipotriene) cream is indicated for the treatment of plaque psoriasis Launch Date2005 |
PubMed
| Title | Date | PubMed |
|---|---|---|
| In vitro metabolism of the anti-psoriatic vitamin D analog, calcipotriol, in two cultured human keratinocyte models. | 1994-02-18 |
|
| Comparison of calcipotriol with selected metabolites and analogues of vitamin D3: effects on cell growth regulation in vitro and calcium metabolism in vivo. | 1993-04-01 |
|
| Comparative effects of a novel vitamin D analogue MC-903 and 1,25-dihydroxyvitamin D3 on alkaline phosphatase activity, osteocalcin and DNA synthesis by human osteoblastic cells in culture. | 1990 |
Patents
Sample Use Guides
Apply a thin layer of Dovonex(R) cream (calcipotriene 0.005%) to the affected skin twice daily and rub in gently and completely. The safety and efficacy of Dovonex(R) Cream have been demonstrated in patients treated for eight weeks.
Route of Administration:
Topical
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/8106449
To study in vitro calcipotriol metabolism human keratinocytes (HPKlA and HPKlA-ras cells) were incubated with 10 uM (123.6 pg total) MC903 for 48 h. Among metabolites of MC903 generated by human keratinocytes, in HPKlA cells, relatively larger proportions of MC1046 (209 ng/10^7 cells/day), and MC1080 (508 ng/10^7 cells/day) were accumulated. In contrast, HPKlA-ras cells had smaller proportions of MC1080 (134 ng/10^7 cells/day) and MC1046 (6.5 ng/10^7 cells/day). Rat osteosarcoma (ROS1712) cells produced 447.9 ng/10^7 cells/day).
| Substance Class |
Chemical
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CHROMATOGRAPHIC PURITY (TLC)
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