| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
| Targets |
PS121912 targets the vitamin D receptor (VDR) and its interaction with the transcriptional coactivator SRC2 (steroid receptor coactivator 2). It functions as a selective inhibitor of this interaction, thereby modulating VDR-mediated gene transcription.
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| ln Vitro |
At low doses, PS121912 functions as a VDR antagonist; however, at high concentrations, it reacts more strongly with the target, resulting in caspase 3/7 activation-mediated intercellular clearance [1]. By attaching to 1,25)-(OH)2D3, PS121912 lowers cyclins A and D's regulatory levels, putting HL-60 tip cells in the S phase or G2/M phase [1].
In vitro, PS121912 exhibits VDR antagonism at low concentrations (0.1-1 µM), inhibiting VDR-mediated transcriptional activity by >70%. At higher concentrations (≥3 µM), it induces caspase 3/7-mediated apoptosis. It shows >34-fold selectivity for VDR over 8 other nuclear receptors. |
| ln Vivo |
PS121912 has exhibited activation stability and can block the enzyme CYP3A4 at greater dosages in in vivo cancer tests [1].
In vivo, PS121912 has acceptable metabolic stability (human liver microsome t1/2=179 min, CLint=2.04 mL/min/kg). It can be used for cancer research. VDR antagonism at low concentrations while inducing apoptosis in cancer cells at higher concentrations has been demonstrated in preclinical models. |
| Enzyme Assay |
VDR-coactivator interaction is assessed using biochemical assays such as AlphaScreen or TR-FRET. VDR protein, a biotinylated SRC2 peptide, and varying concentrations of PS121912 are incubated. The interaction between VDR and SRC2 is measured by signal intensity. IC50 values for inhibition of the interaction are calculated. VDR transcriptional activity is assessed using a luciferase reporter gene assay.
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| Cell Assay |
Cell Viability Assay[1]
Cell Types: Cancer cells composed of DU145 (prostate), Caco2 (colon), HL-60 (monocytes) and SKOV3 (ovary) Tested Concentrations: 0-100 μM Incubation Duration: 18 hrs (hours) Experimental Results: Induction of all Four types of cancer cells undergo apoptosis, among which HL-60 cells are the most sensitive. Cell proliferation assay[1] Cell Types: Four different cancer cell lines (DU145 prostate cancer, Caco2 colon cancer, SKOV3 ovarian cancer, and HL-60 monocytes) Tested Concentrations: 0.5, 2 μM Incubation Duration: 5 days Experimental Results: Zoom The growth inhibition of cancer cells caused by submicromolar concentrations of 1.25-(OH)2D itself does not have an anti-proliferative effect. Apoptosis analysis [1] Cell Types: HL-60 Cell Tested Concentrations: 500 nM Incubation Duration: 18 hrs (hours) Experimental Results: HSP60 and Survivin expression diminished, and pro-apoptotic BIM levels increased. RT-PCR[1] Cell Types: HL-60 Cell Tested Concentrations: 3 μM Incubation Duration: 18 h Experimental Results: Induced expression of caspase 3 and caspase 7 mRNA levels. For cellular assays, cancer cell lines (e.g., breast, prostate, colon) are seeded in 96-well plates and treated with PS121912 at varying concentrations (0.01-10 µM) for 24-72 hours. Cell viability is assessed by MTT or CellTiter-Glo assay. Apoptosis is evaluated by flow cytometry using Annexin V/PI staining or by caspase-3/7 activity assays. VDR target gene expression is measured by qRT-PCR. |
| Animal Protocol |
For in vivo efficacy studies, immunocompromised mice bearing tumor xenografts are treated with PS121912 orally or intraperitoneally at doses of 1-50 mg/kg. Tumor volume is measured by caliper twice weekly. Tumors are excised for analysis of VDR target gene expression and apoptosis markers. Pharmacokinetic parameters are determined from plasma concentration measurements.
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| References |
| Molecular Formula |
C24H21F3N2O
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|---|---|
| Molecular Weight |
410.43
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| Exact Mass |
410.16
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| CAS # |
1529814-60-5
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| PubChem CID |
73334809
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
6.5
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
30
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| Complexity |
541
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C(C1C=CC(OC)=CC=1)(C1=C(NC2=CC=CC=C12)C)NC1C=CC(C(F)(F)F)=CC=1
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| InChi Key |
NNTQFFZNUZBJND-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C24H21F3N2O/c1-15-22(20-5-3-4-6-21(20)28-15)23(16-7-13-19(30-2)14-8-16)29-18-11-9-17(10-12-18)24(25,26)27/h3-14,23,28-29H,1-2H3
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| Chemical Name |
N-[(4-methoxyphenyl)-(2-methyl-1H-indol-3-yl)methyl]-4-(trifluoromethyl)aniline
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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 |
| 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 (~243.65 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.09 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 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 25.0 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4365 mL | 12.1823 mL | 24.3647 mL | |
| 5 mM | 0.4873 mL | 2.4365 mL | 4.8729 mL | |
| 10 mM | 0.2436 mL | 1.2182 mL | 2.4365 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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