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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
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 6 / 6
E/Z Centers 3
Optical Activity UNSPECIFIED

Description
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

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Dovonex

Approved Use

Dovonex (calcipotriene, MC-1046 is an active metabolite of calcipotriene) cream is indicated for the treatment of plaque psoriasis

Launch Date

1.11464638E12
PubMed

PubMed

TitleDatePubMed
Patents

Patents

Sample Use Guides

In Vivo Use Guide
Curator's Comment: MC-1046 is an active metabolite of calcipotriene
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
Created
by admin
on Sat Dec 16 01:39:50 UTC 2023
Edited
by admin
on Sat Dec 16 01:39:50 UTC 2023
Record UNII
G70BS4HF9Z
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
MC-1046
Common Name English
CALCIPOTRIOL IMPURITY A [EP IMPURITY]
Common Name English
CALCIPOTRIENE IMPURITY A [USP IMPURITY]
Common Name English
9,10-SECOCHOLA-5,7,10(19),22-TETRAEN-24-ONE, 24-CYCLOPROPYL-1,3-DIHYDROXY-, (1.ALPHA.,3.BETA.,5Z,7E,22E)-
Common Name English
CALCIPOTRIOL MONOHYDRATE IMPURITY A [EP IMPURITY]
Common Name English
MC 1046
Common Name English
(5Z,7E,22E)-24-CYCLOPROPYL-1.ALPHA.,3.BETA.-DIHYDROXY-9,10-SECOCHOLA-5,7,10(19),22-TETRAEN-24-ONE
Common Name English
Code System Code Type Description
FDA UNII
G70BS4HF9Z
Created by admin on Sat Dec 16 01:39:50 UTC 2023 , Edited by admin on Sat Dec 16 01:39:50 UTC 2023
PRIMARY
PUBCHEM
9547342
Created by admin on Sat Dec 16 01:39:50 UTC 2023 , Edited by admin on Sat Dec 16 01:39:50 UTC 2023
PRIMARY
CAS
126860-83-1
Created by admin on Sat Dec 16 01:39:50 UTC 2023 , Edited by admin on Sat Dec 16 01:39:50 UTC 2023
PRIMARY
Related Record Type Details
PARENT -> METABOLITE
Related Record Type Details
PARENT -> IMPURITY
PARENT -> IMPURITY
CHROMATOGRAPHIC PURITY (TLC)
USP