| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg | |||
| Other Sizes |
| Targets |
Seocalcitol targets the vitamin D receptor (VDR), a nuclear receptor that functions as a transcription factor upon ligand binding. VDR is expressed in normal vitamin D-responsive tissues but is also overexpressed in certain cancers, including hepatocellular carcinoma and pancreatic cancer. Upon binding to VDR, seocalcitol induces conformational changes that promote heterodimerization with the retinoid X receptor (RXR) and subsequent recruitment of coactivators. This leads to the transcriptional regulation of genes involved in cell proliferation, differentiation, apoptosis, and calcium homeostasis. Seocalcitol's reduced calcemic activity compared to calcitriol is attributed to its altered binding affinity and differential regulation of VDR target genes. Its anti-tumor activity is mediated through the induction of cell cycle arrest and apoptosis in cancer cells.
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| ln Vitro |
In mouse bone marrow cultures, osteoclast recruitment is stimulated by seocalcitol (EB 1089), with an EC50 of 0.1 nM. Bone resorption is stimulated by osteocalcitol, whose estimated EC50 is 0.03 nM[1]. In the kidney, seocalcitol (EB 1089) increases 24-carboxylase mRNA in a dose-dependent manner (EC50=0.4±0.13). Seocalcitol has a Kd value of 0.48±0.04 nM in the bridge. Seocalcitol's Kd in the bridge, however, is 1.43±0.19 nM)[2]. Cellular secretion is dose-dependently induced by seocalcitol (0.1–10 nM). Compared to 1 nM VD3, 1 nM Seocalcitol (EB 1089) was associated with higher lactation activity.
Seocalcitol demonstrates potent in vitro anti-proliferative activity across multiple cancer cell lines. It is 60 times more potent than calcitriol in inhibiting the growth of MCF-7 breast cancer cells. The compound induces autophagy in MCF-7 cells, a process that may contribute to its anti-tumor effects. Seocalcitol inhibits the proliferation of human laryngeal squamous carcinoma cells through the upregulation of p57, a cyclin-dependent kinase inhibitor. It also reverses the effects of parathyroid hormone-related protein (PTHrP), which is involved in cancer-associated hypercalcemia and bone metastasis. Additionally, seocalcitol has been shown to inhibit the parathyroid hormone-related protein-enhanced bone metastasis and xenograft growth of human prostate cancer cells. Its anti-proliferative effects are mediated through VDR-dependent transcriptional regulation and induction of cell cycle arrest. |
| ln Vivo |
Compared to 1,25 (OH) 2VD3, the synthetic vitamin D analog seocalcitol (EB1089) has less hypercalcemic action. At a daily dose of 0.5 μg/kg body weight, theocalcidol, a long-term intraperitoneal (IP) product of C3H/Sy, had a strong inhibitory impact on the development of hepatocellular carcinoma (HCC) in a different investigation [4]. At 4 to 12 days of age (P4 to P12), theocalciferol (EB 1089) was given intraperitoneally at a dose of 0.38 or 1.25 μg/kg body weight (BW)/day, with daily doses in the postpartum reserve. Merely the maximum dosage of ceciocalcidol (1.25 μg/kg BW) greatly decreased weight growth when utilized either by itself or in conjunction with tretinoin, all-trans retinoic acid (RA), or dexamethasone [5].
In vivo, seocalcitol has demonstrated significant anti-tumor activity in various xenograft models. It inhibits the growth of human prostate cancer xenografts and reduces bone metastasis in preclinical models. In a human model of squamous cancer, seocalcitol reversed hypercalcemia, a common complication of advanced cancer. However, in neonatal rat lung studies, the analog was found to impair alveolarization and induce localized regions of increased fibroblast density, indicating potential developmental toxicity. Seocalcitol has also been shown to convert CD4+ T cells to Foxp3+ regulatory T cells in patients with ulcerative colitis, suggesting immunomodulatory properties. The compound's reduced calcemic activity compared to calcitriol makes it a more favorable candidate for long-term cancer therapy. |
| Enzyme Assay |
In vitro enzyme/receptor binding assays for seocalcitol typically involve competitive binding to the vitamin D receptor (VDR). The assay uses radiolabeled calcitriol ([3H]-1,25(OH)2D3) as a tracer, which is incubated with VDR protein and varying concentrations of seocalcitol. After incubation, bound and free radioligand are separated using charcoal-dextran precipitation or filtration methods, and radioactivity is measured by liquid scintillation counting. The binding affinity (Kd or IC50) is calculated from the displacement curve. Seocalcitol's binding affinity is compared to that of calcitriol to determine relative potency. The assay is performed in buffer containing appropriate salts and stabilizers to maintain VDR integrity, typically at 4degC for several hours to reach equilibrium. Non-specific binding is determined using a large excess of unlabeled calcitriol.
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| Cell Assay |
In vitro cellular assays for seocalcitol are performed using various cancer cell lines that express VDR, including MCF-7 (breast cancer), LNCaP (prostate cancer), and HepG2 (hepatocellular carcinoma) cells. Cells are cultured in appropriate medium and treated with seocalcitol at concentrations ranging from picomolar to micromolar for 24-96 hours. Cell proliferation is assessed using assays such as MTT, CellTiter-Glo, or BrdU incorporation. Apoptosis is measured using annexin V/propidium iodide staining, caspase activity assays, or TUNEL staining. Autophagy induction is detected by LC3-II accumulation and puncta formation observed by fluorescence microscopy. Gene expression changes are analyzed by qRT-PCR and Western blot for VDR target genes including p21, p27, and CYP24A1. Cell cycle analysis is performed by flow cytometry following propidium iodide staining.
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| Animal Protocol |
In vivo animal studies for seocalcitol are conducted using immunodeficient mice bearing human tumor xenografts. Typically, 6-8 week old female athymic nude mice are implanted subcutaneously with cancer cells. Once tumors reach a predetermined size (e.g., 100-200 mm3), animals are randomized into treatment groups and administered seocalcitol via oral gavage or intraperitoneal injection at various doses and schedules. Tumor size is measured twice weekly using calipers, and body weight is monitored as a safety indicator. At study termination, tumors are excised, weighed, and processed for histopathological analysis or biomarker assessment. Bone metastasis models may involve intracardiac injection of cancer cells, followed by assessment of osteolytic lesions by X-ray or micro-CT. Serum calcium levels are monitored to assess hypercalcemic effects. Pharmacokinetic samples are collected at multiple time points to determine drug exposure.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of seocalcitol have been characterized in preclinical studies. The compound is administered orally and exhibits good bioavailability in animal models. Seocalcitol is metabolized primarily by CYP24A1, the enzyme responsible for vitamin D catabolism, which is upregulated upon VDR activation. The compound has a longer half-life compared to calcitriol due to its resistance to metabolic degradation. Seocalcitol shows extensive tissue distribution, consistent with its lipophilic nature (logP values typical of vitamin D analogs). The compound is soluble in DMSO and ethanol, making it suitable for both in vitro and in vivo administration. Its reduced calcemic activity is attributed to differential tissue distribution and altered VDR-mediated gene regulation compared to calcitriol. The compound's pharmacokinetic profile supports once-daily dosing in preclinical studies.
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| Toxicity/Toxicokinetics |
Seocalcitol exhibits a more favorable toxicity profile compared to calcitriol, with reduced hypercalcemic effects. However, like all vitamin D analogs, it can cause dose-dependent hypercalcemia, hypercalciuria, and soft tissue calcification at high doses. In neonatal rat studies, seocalcitol impaired alveolarization and induced localized regions of increased fibroblast density in the lung, indicating potential developmental and pulmonary toxicity. Standard toxicology studies in rodents and non-human primates have evaluated the compound's safety profile for potential therapeutic applications. Parameters assessed include clinical observations, body weight, food consumption, serum calcium and phosphorus levels, organ weights, and histopathology. The compound has been investigated in clinical trials for cancer indications, where dose-limiting toxicities were primarily related to hypercalcemia. Comprehensive toxicity data are available from preclinical and clinical studies, but seocalcitol has not received regulatory approval for any indication.
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| References |
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| Additional Infomation |
Theoxacillin is a vitamin D3 analog with potential antitumor activity. Theoxacillin binds to and activates the vitamin D receptor. The vitamin D receptor is a cytoplasmic polypeptide expressed in normal vitamin D-responsive tissues, but it is also overexpressed in certain cancers, including hepatocellular carcinoma and pancreatic cancer. Theoxacillin induces cancer cell differentiation, inhibits cancer cell growth, and induces apoptosis through vitamin D receptor-mediated mechanisms. Furthermore, theoxacillin may also induce cell growth arrest and apoptosis independently of vitamin D receptor activation through some mechanisms that are not yet fully elucidated.
Seocalcitol (EB1089) is a synthetic vitamin D analog developed as an anti-cancer agent with reduced calcemic side effects. It is a VDR agonist that is 50-200 times more potent than calcitriol at inhibiting cell proliferation. The compound has been investigated in clinical trials for hepatocellular carcinoma and other solid tumors. Its mechanism of action involves VDR-mediated transcriptional regulation of genes controlling cell cycle progression, apoptosis, and differentiation. Seocalcitol has been shown to induce autophagy and apoptosis in cancer cells through both genomic and non-genomic VDR signaling pathways. Despite promising preclinical data, seocalcitol has not received regulatory approval for any indication, likely due to challenges in achieving therapeutic efficacy without unacceptable hypercalcemia. The compound remains a valuable research tool for studying vitamin D biology and developing improved VDR-targeted therapies. Its chemical formula is C30H46O3 with a molecular weight of 454.68 g/mol. |
| Molecular Formula |
C₃₀H₄₆O₃
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|---|---|
| Molecular Weight |
454.68
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| Exact Mass |
454.344
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| CAS # |
134404-52-7
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| PubChem CID |
5288149
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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 |
608.5±55.0 °C at 760 mmHg
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| Flash Point |
252.3±26.1 °C
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| Vapour Pressure |
0.0±4.0 mmHg at 25°C
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| Index of Refraction |
1.560
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| LogP |
7.02
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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 |
7
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| Heavy Atom Count |
33
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| Complexity |
812
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| Defined Atom Stereocenter Count |
6
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| SMILES |
CCC(CC)(/C=C/C=C/[C@@H](C)[C@H]1CC[C@@H]\2[C@@]1(CCC/C2=C\C=C/3\C[C@H](C[C@@H](C3=C)O)O)C)O
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| InChi Key |
LVLLALCJVJNGQQ-SEODYNFXSA-N
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| InChi Code |
InChI=1S/C30H46O3/c1-6-30(33,7-2)18-9-8-11-21(3)26-15-16-27-23(12-10-17-29(26,27)5)13-14-24-19-25(31)20-28(32)22(24)4/h8-9,11,13-14,18,21,25-28,31-33H,4,6-7,10,12,15-17,19-20H2,1-3,5H3/b11-8+,18-9+,23-13+,24-14-/t21-,25-,26-,27+,28+,29-/m1/s1
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| Chemical Name |
(1R,3S,5Z)-5-[(2E)-2-[(1R,3aS,7aR)-1-[(2R,3E,5E)-7-ethyl-7-hydroxynona-3,5-dien-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 |
EB 1089EB-1089EB1089
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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. |
| 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 : ≥ 50 mg/mL (~109.97 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.50 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 25.0 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. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.50 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 25.0 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 | 2.1993 mL | 10.9967 mL | 21.9935 mL | |
| 5 mM | 0.4399 mL | 2.1993 mL | 4.3987 mL | |
| 10 mM | 0.2199 mL | 1.0997 mL | 2.1993 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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