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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
Structure of MC-1046

SMILES

[H][C@@]1(CC[C@@]2([H])\C(CCC[C@]12C)=C\C=C3\C[C@@H](O)C[C@H](O)C3=C)[C@H](C)\C=C\C(=O)C4CC4

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

HIDE SMILES / InChI

Molecular Formula C27H38O3
Molecular Weight 410.5888
Charge 0
Count
MOL RATIO 1 MOL RATIO (average)
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 6 / 6
E/Z Centers 3
Optical Activity UNSPECIFIED

Description

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.

Originator

Approval Year

Targets

Primary TargetPharmacologyConditionPotency

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Dovonex

PubMed

Patents

Sample Use Guides

In Vivo Use Guide
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
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
Record UNII
G70BS4HF9Z
Record Status Validated (UNII)
Record Version