| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
Impurity F of Calcipotriol is an impurity of Calcipotriol (MC 903; Calcipotriene) which is a synthetic calcitriol/Vitamin D3 (VD3) analog and an agonist of the VD3 receptor. It is used in the treatment of psoriasis and marketed under the trade name Dovonex. It has comparable affinity with calcitriol (Vit. D) for the Vitamin D receptor (VDR), while being less than 1% as active as the calcitriol in regulating calcium metabolism. Chronic plaque psoriasis is the chief medical use of calcipotriol. It has also been used successfully in the treatment of alopecia areata.
| Targets |
VDR/vitamin D receptor.
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|---|---|
| ln Vitro |
Calcipotriol is a novel vitamin D3 analogue developed for topical treatment of psoriasis. Calcipotriol is believed to act via regulation of cell proliferation and differentiation. In this respect calcipotriol is as potent as 1 alpha, 25(OH)2D3, the physiologically active form of vitamin D3, but its calcaemic activity in vivo is 100 to 200 times lower. In the present investigation, the effects of calcipotriol on cell growth regulation in vitro and on calcium metabolism in vivo were compared to those exerted by a number of metabolites and analogues of vitamin D3. Besides 1 alpha, 25(OH)2D3, these included the two physiologically occurring metabolites 25(OH)D3 and 24,25(OH)2D3, and the two synthetic analogues 1 alpha (OH)D3 and 1 alpha, 24(OH)2D3. 25(OH)D3 and 24,25(OH)2D3 were shown to be inactive both in vitro and in vivo. 1 alpha (OH)D3 was found to have a low biological activity in vitro, but was highly calcaemic in vivo after biotransformation to 1 alpha, 25(OH)2D3. Calcipotriol, 1 alpha, 24(OH)2D3 and 1 alpha, 25(OH)2D3 were all three potent regulators of cell proliferation and differentiation in vitro. In vivo, only calcipotriol showed a greatly reduced calcaemic activity after both oral and intravenous administration. It is concluded that calcipotriol, with a reduced risk of inducing calcaemic side-effects upon absorption from the skin, possesses a favourable therapeutic profile for topical treatment of hyperproliferative diseases[1].
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| References |
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| Additional Infomation |
1α,24-Dihydroxyvitamin D2 (1α,24(OH)2D2) is a metabolite of 1α-hydroxyvitamin D2 (1α-OH-D2), a prodrug under development for the treatment of secondary hyperparathyroidism in end-stage renal disease. This prodrug has a wider therapeutic index than its corresponding vitamin D3 analogue, likely because at high doses, the hepatic metabolic pathway of 1α-OH-D2 is converted from 1α,25-dihydroxyvitamin D2 (1α,25(OH)2D2) to 1α,24(OH)2D2. This report describes the pharmacokinetics of 1α,24(OH)2D2 in rats and its systemic effects on serum and urinary calcium. These properties are compared with 1α,25(OH)₂D₂, calcitriol (the active metabolite of endogenous vitamin D₃), and calcipotriol, a vitamin D analogue known for its rapid clearance and minimal impact on calcium homeostasis. A comparison of blood concentration curves from zero to infinity shows that the systemic exposure of 1α,24(OH)₂D₂ is approximately one-fifth that of 1α,25(OH)₂D₂ or calcitriol, but almost 30 times that of calcipotriol. The oral bioavailability and circulating half-life of 1α,24(OH)₂D₂ and calcitriol are similar, while those of calcipotriol are much lower. In vitamin D-deficient rats, oral administration of both 1α,25(OH)₂D₂ and calcitriol induced a dose-dependent increase in serum calcium levels, while a similar response was achieved with oral administration of 1α,24(OH)₂D₂ at a dose 30 times higher. Dose-response curves plotted after oral and subcutaneous injection of 1α,24(OH)₂D₂, calcitriol and calcipotriol in normal rats showed that 1α,24(OH)₂D₂ increased serum and urinary calcium levels to a much lesser extent than calcitriol, but slightly more than calcipotriol. These properties of 1α,24(OH)₂D₂ suggest that the formation of this metabolite from 1α-OH-D₂ helps reduce the toxicity of 1α-OH-D₂ and suggests that 1α,24(OH)₂D₂ itself has therapeutic potential. [2]
1,25-dihydroxyvitamin D3 analogues with an inverted configuration at C-1 or C-24 in the side chain and an E or Z double bond at C-22 or C-5 in the triene system were studied in vitro for their antiproliferative activity against a variety of human cancer cell lines. Analogs coded PRI-2201 (calcipotriol), PRI-2202, and PRI-2205, as well as calcipotriol and tacalcitol (used as control drugs), showed antiproliferative activity against human HL-60, HL-60/MX2, MCF-7, T47D, SCC-25, and mouse WEHI-3 cancer cell lines. In vivo toxicity studies showed that PRI-2202 and PRI-2205 were less toxic than the control drugs. No changes in body weight were observed even after administration at a total dose of 2.5–5.0 mg/kg over 5 consecutive days. Calcipotriol and tacalcitol showed toxicity at doses 100 times lower than the control drugs under the same dosing regimen. Calcipotriol was lethal to all mice after administration of a total dose of 5.0 mg/kg. Compared to calcipotriol, calcipotriol, or PRI-2202, the analog PRI-2205 appeared to be more effective in inhibiting the growth of Levis lung cancer tumors in mice. This analogue did not show calcification activity at doses that inhibited tumor growth in vivo, nor at higher doses. [3] |
| Molecular Formula |
C39H68O3SI2
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|---|---|
| Molecular Weight |
641.12642
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| Exact Mass |
640.471
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| CAS # |
112875-61-3
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| Related CAS # |
Calcipotriol;112965-21-6
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| PubChem CID |
13917667
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| Appearance |
White to off-white solid powder
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| LogP |
11.149
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
11
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| Heavy Atom Count |
44
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| Complexity |
1130
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| Defined Atom Stereocenter Count |
7
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| SMILES |
C[C@H](/C=C/[C@H](C1CC1)O)[C@H]2CC[C@@H]\3[C@@]2(CCC/C3=C\C=C\4/C[C@H](C[C@@H](C4=C)O[Si](C)(C)C(C)(C)C)O[Si](C)(C)C(C)(C)C)C
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| InChi Key |
DIMYHZDULFSWLS-YFSXTQNDSA-N
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| InChi Code |
InChI=1S/C39H68O3Si2/c1-27(16-23-35(40)30-18-19-30)33-21-22-34-29(15-14-24-39(33,34)9)17-20-31-25-32(41-43(10,11)37(3,4)5)26-36(28(31)2)42-44(12,13)38(6,7)8/h16-17,20,23,27,30,32-36,40H,2,14-15,18-19,21-22,24-26H2,1,3-13H3/b23-16+,29-17+,31-20+/t27-,32-,33-,34+,35-,36+,39-/m1/s1
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| Chemical Name |
(E,1S,4R)-4-[(1R,3aS,4E,7aR)-4-[(2E)-2-[(3S,5R)-3,5-bis[[tert-butyl(dimethyl)silyl]oxy]-2-methylidenecyclohexylidene]ethylidene]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-1-yl]-1-cyclopropylpent-2-en-1-ol
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| Synonyms |
Impurity F of Calcipotriol; Calcipotriol Impurity F; Impurity of Calcipotriol; 4SP93VP62P; (5Z,7E,22E,24S)-24-Cyclopropyl-1alpha,3beta-bis(((1,1-dimethylethyl)dimethylsilyl)oxy)-9,10-secochola-5,7,10(19),22-tetraen-24-ol; (E,1S,4R)-4-[(1R,3aS,4E,7aR)-4-[(2Z)-2-[(3S,5R)-3,5-bis[[tert-butyl(dimethyl)silyl]oxy]-2-methylidenecyclohexylidene]ethylidene]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-1-yl]-1-cyclopropylpent-2-en-1-ol; UNII-4SP93VP62P;
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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 Note: (1). This product requires protection from light (avoid light exposure) during transportation and storage. (2). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. (3). This product is not stable in solution, please use freshly prepared working solution for optimal results. |
| 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) |
DMSO : ~25 mg/mL (~38.99 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.25 mg/mL (1.95 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 12.5 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 1.25 mg/mL (1.95 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 12.5 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.5597 mL | 7.7987 mL | 15.5975 mL | |
| 5 mM | 0.3119 mL | 1.5597 mL | 3.1195 mL | |
| 10 mM | 0.1560 mL | 0.7799 mL | 1.5597 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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