![Tacalcitol [1,24(R)-Dihydroxyvitamin D3]](/upload/0201/CgAH6F3JVJaAXFzMAAAVdQ7SbmE551.png)
| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg | |||
| 25mg | |||
| 50mg | |||
| Other Sizes |
Purity: ≥98%
| Targets |
Vitamin D receptor (VDR). In competitive binding assays using cytosolic extracts of cultured human keratinocytes, the concentration of Tacalcitol required to displace 50% of specific [3H]1,25(OH)2D3 binding was 3×10⁻¹¹ M, compared to 6×10⁻¹¹ M for 1,25(OH)2D3, indicating a slightly higher affinity for the receptor. [6]
As a vitamin D analog, Tacalcitol primarily targets the vitamin D receptor (VDR), a nuclear receptor that regulates gene expression. Upon binding to VDR, it forms a heterodimer with the retinoid X receptor (RXR) and binds to vitamin D response elements (VDREs) in the promoter regions of target genes. This leads to the modulation of genes involved in cell proliferation, differentiation, and immune function, which are key to its therapeutic effect in psoriasis. |
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| ln Vitro |
In human nasal polyp fibroblast cultures stimulated with LPS, Tacalcitol at 10⁻⁴ M significantly inhibited IL-6 synthesis (mean 3616.61 pg/ml, p=0.0005) compared to LPS-stimulated control (6120.17 pg/ml), and inhibited IL-8 synthesis (mean 5859.50 pg/ml, p=0.0005) compared to LPS-stimulated control (37786.67 pg/ml). At concentrations of 10⁻⁷, 10⁻⁶, and 10⁻⁵ M, no statistically significant inhibition was observed. In healthy nasal mucosa fibroblasts, Tacalcitol at 10⁻⁴ M also significantly reduced IL-6 (p=0.008) and IL-8 (p=0.001) [3].
In vitro, Tacalcitol has been shown to inhibit cancer cell proliferation and migration. It decreases the secretion of eotaxin and RANTES in nasal polyp fibroblasts. It also modulates immunological and inflammatory processes. As a vitamin D analog, it regulates the expression of genes involved in cell cycle control, differentiation, and apoptosis. It induces nerve growth factor (NGF) production in epidermal keratinocytes, which may contribute to its effects on skin. |
| ln Vivo |
In a 7-year-old Japanese boy with segmental vitiligo on the left eyelid, topical application of Tacalcitol ointment (20 μg/g) once daily to the lesion and surrounding area (including left upper cheek) for 9 months, with sun exposure, resulted in moderate repigmentation at 6 months, but also caused hyperpigmented spots (freckles) on the left cheek to increase in number and intensity, which worsened further by 9 months. Dermoscopy showed irregular borders. The freckling was attributed to Tacalcitol treatment [4].
In vivo, Tacalcitol is used topically for the treatment of mild to moderate plaque psoriasis. It works by modulating the proliferation and differentiation of keratinocytes and by exerting immunomodulatory effects on T-cells and dendritic cells in the skin. It can also promote normal bone growth by regulating calcium and phosphate homeostasis, though for psoriasis treatment, systemic effects on calcium are minimal. |
| Enzyme Assay |
Competitive binding assay: The cytosolic fraction of cultured human keratinocytes was prepared by homogenization in Tris-HCl buffer (50 mM, pH 7.4) containing 300 mM KCl, 10 mM EDTA, 5 mM dithiothreitol, 10 mM sodium molybdate, and 3 mM phenylmethylsulfonyl fluoride, followed by centrifugation at 105,000×g for 1 h. The supernatant was incubated with 9.8 pg (23.6 fmol, 9200 dpm) of [3H]1,25(OH)2D3 and various concentrations of unlabeled Tacalcitol or 1,25(OH)2D3 for 1 h at 25°C. Specific binding was determined by subtracting non-specific binding from total binding. The amount of [3H]1,25(OH)2D3 specifically bound in the absence of competitor was defined as control binding. The concentration of Tacalcitol required to displace 50% of control binding was 3×10⁻¹¹ M. [6]
In vitro receptor binding assays for Tacalcitol typically involve competitive binding to the vitamin D receptor (VDR). Radiolabeled 1,25-dihydroxyvitamin D3 is used as a tracer, and its displacement by various concentrations of Tacalcitol is measured. The assay is performed in a buffer containing the VDR protein, and the IC₅₀ is calculated to determine the compound's affinity for the receptor. |
| Cell Assay |
Human nasal polyp fibroblasts (passages 6-9) were cultured in RPMI 1640 medium with 10% fetal bovine serum, penicillin (1000 UI/ml) and streptomycin (10 mg/ml). Cells were seeded at 5000 cells per well in 96-well plates. After 24 hours of incubation, bacterial LPS (E. coli) at 10 ng/ml was added and cultures continued for another 24 hours. Then Tacalcitol at concentrations of 10⁻⁷, 10⁻⁶, 10⁻⁵, and 10⁻⁴ M was added. After 24 hours of treatment, culture supernatants were collected and IL-6 and IL-8 concentrations were measured by ELISA according to the manufacturer's protocols. Absorbance was read at 450 nm. Control groups included cultures stimulated with LPS but not treated with Tacalcitol, and unstimulated cultures without LPS. From the time of LPS stimulation onward, the culture medium did not contain fetal bovine serum [3].
In vitro cell-based assays for Tacalcitol are often performed using keratinocyte cell lines. Cells are treated with varying concentrations of the compound, and its effects on cell proliferation (e.g., by MTT assay) and differentiation (e.g., by measuring the expression of markers like involucrin or transglutaminase) are assessed. Its anti-inflammatory activity can be evaluated in immune cells by measuring the production of cytokines like IL-8 or TNF-α. |
| Animal Protocol |
In vivo animal studies for Tacalcitol are conducted in models of psoriasis, such as the imiquimod-induced psoriasis-like dermatitis model in mice. The compound is typically applied topically, and its efficacy is assessed by measuring skin thickness, erythema, and scaling, as well as by histological analysis of skin sections for inflammatory infiltrates and keratinocyte proliferation.
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| ADME/Pharmacokinetics |
Specific pharmacokinetic data for Tacalcitol are not extensively detailed in the provided literature. As a topical treatment for psoriasis, systemic absorption is generally low, minimizing systemic side effects. The compound is available as an ointment and is applied to the affected skin once or twice daily. It is soluble in DMSO at 100 mg/mL.
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| Toxicity/Toxicokinetics |
Topical application of Tacalcitol (20 μg/g ointment) once daily for 9 months to the left eyelid and cheek of a 7-year-old boy caused freckling and worsening of existing freckles on the treated area. No inflammation occurred on or around the affected lesion. The effect was attributed to the vitamin D3 analog's ability to influence melanocyte maturation and differentiation and to up-regulate melanogenesis [4].
The primary adverse effect of Tacalcitol is local skin irritation, which can include redness, burning, and itching at the application site. Systemic effects, such as hypercalcemia, are rare but possible if the drug is used over large body surface areas or in combination with other Vitamin D analogs. It is contraindicated in patients with severe hypercalcemia or known hypersensitivity to the drug. |
| References |
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| Additional Infomation |
Tacalcitol is a hydroxyl-opening sterol, belonging to the calcium alcohol class of compounds, with hydroxyl groups at both the 1S and 24R positions. It is a vitamin D3 analog used to treat adult psoriasis vulgaris, particularly scalp psoriasis. It possesses anti-psoriatic, vitamin D receptor agonist, and antitumor effects. Tacalcitol belongs to the vitamin D3 class of compounds and is a hydroxyl-opening sterol, secondary alcohol, and open-ring cholesterol sterol. Its functions are related to those of calcium alcohol compounds.
Tacalcitol is a vitamin D3 analog used topically for psoriasis and vitiligo. It may promote melanocyte maturation and upregulate melanogenesis. Dermatologists should be aware that topical application of Tacalcitol to the cheeks can cause freckling and worsen existing freckles in predisposed children [4]. In nasal polyp fibroblasts, Tacalcitol shows anti-inflammatory effects by reducing IL-6 and IL-8 at high concentration (10⁻⁴ M) [3]. As a vitamin D3 analog, Tacalcitol is effective in treating plaque psoriasis by modulating keratinocyte proliferation and differentiation. It is available as a topical ointment. Its mechanism of action involves binding to the vitamin D receptor (VDR), which regulates gene expression involved in cell proliferation and immune modulation. It is for research and therapeutic use. |
| Molecular Formula |
C27H44O3
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| Molecular Weight |
416.646
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| Exact Mass |
416.329
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| Elemental Analysis |
C, 77.84; H, 10.65; O, 11.52
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| CAS # |
57333-96-7
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| Related CAS # |
Tacalcitol monohydrate;93129-94-3
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| PubChem CID |
5283734
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| Appearance |
White to off-white solid powder
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| Density |
1.1±0.1 g/cm3
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| Boiling Point |
565.0±50.0 °C at 760 mmHg
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| Flash Point |
238.4±24.7 °C
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| Vapour Pressure |
0.0±3.5 mmHg at 25°C
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| Index of Refraction |
1.546
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| LogP |
6.12
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
30
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| Complexity |
676
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| Defined Atom Stereocenter Count |
7
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| SMILES |
C=C1[C@H](C[C@@H](C/C1=C/C=C2[C@]3([C@@](C)([C@H](CC3)[C@@H](CC[C@H](C(C)C)O)C)CCC/2)[H])O)O
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| InChi Key |
BJYLYJCXYAMOFT-RSFVBTMBSA-N
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| InChi Code |
InChI=1S/C27H44O3/c1-17(2)25(29)13-8-18(3)23-11-12-24-20(7-6-14-27(23,24)5)9-10-21-15-22(28)16-26(30)19(21)4/h9-10,17-18,22-26,28-30H,4,6-8,11-16H2,1-3,5H3/b20-9+,21-10-/t18-,22-,23-,24+,25-,26+,27-/m1/s1
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| Chemical Name |
(1R,3S,5Z)-5-[(2E)-2-[(1R,3aS,7aR)-1-[(2R,5R)-5-hydroxy-6-methylheptan-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,3-diol
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| Synonyms |
PRI2191; TV 02; PRI-2191; TV-02; 1,24(R)-Dihydroxyvitamin D3; 1.alpha.,24R-Dihydroxyvitamin D3; Bonalfa; Curatoderm; PRI 2191; TV02;
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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: ≥ 100 mg/mL (~240.0 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.75 mg/mL (6.60 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 27.5 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: ≥ 2.75 mg/mL (6.60 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 27.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.75 mg/mL (6.60 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4001 mL | 12.0005 mL | 24.0010 mL | |
| 5 mM | 0.4800 mL | 2.4001 mL | 4.8002 mL | |
| 10 mM | 0.2400 mL | 1.2000 mL | 2.4001 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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