| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| Other Sizes |
| ln Vitro |
PROTAC AR Degrader-12 (Compound 18o) showed good inhibitory activity against MCF-7 (IC50 = 0.13 μM) and LCC2 cells (IC50 = 0.54 μM), and had broad-spectrum efficacy against clinically relevant mutants. It showed strong sub-micromolar inhibitory effects against MCF-7D538G (IC50 = 0.66 μM), MCF-7Y537S (IC50 = 0.44 μM) and MCF-7EGFR (IC50 = 0.52 μM) [1]. PROTAC AR Degrader-12 (0.01-2 μM, 24 hours) can effectively degrade AR protein in MCF-7 cells (DC50 = 0.72 μM) in a dose-dependent manner [1]. PROTAC AR Degrader-12 (1 μM, 0–24 h) showed a time-dependent effect on the degradation of AR in MCF-7 cells[1]. PROTAC AR Degrader-12 (0.01–2 μM, 24 h) led to a concentration-dependent downregulation of ERα protein expression in MCF-7 cells[1]. PROTAC AR Degrader-12 (0.01–2 μM, 12–24 h) significantly downregulated ERα protein expression in MCF-7D538G, MCF-7Y537S, MCF-7EGFR, LCC2, and T47D cells, but failed to downregulate ERβ protein expression in PC9 cells[1]. PROTAC AR Degrader-12 (1 μM, 24 h) induced a reduction in ERα through an indirect mechanism rather than directly targeting the degradation of CBS in MCF-7 cells[1]. PROTAC AR Degrader-12 (0-5 μM, 0-24 h) reduces the expression of AR protein in MCF-7 cells through posttranscriptional degradation, while the reduction of ERα is due to transcriptional repression [1]. PROTAC AR Degrader-12 showed potent antiproliferative activity in AR-overexpressing but ERα-deficient prostate cancer cells LNCaP (IC50 = 0.46 μM), but its antiproliferative activity was significantly reduced in AR-negative MDA-MB-231 cells (IC50 > 30 μM) [1]. PROTAC AR Degrader-12 can effectively stabilize AR protein at high temperature, but has a weak protective effect on ERα protein, which indicates that PROTAC AR Degrader-12 binds to AR in LCC2 cells but not to ERα [1]. PROTAC AR Degrader-12 (1 μM, 24 h) significantly inhibited the mRNA expression of FOXA1, GREB1, SRC and PELP1 in MCF-7 cells [1]. PROTAC AR Degrader-12 (1-10 μM, 48 h) induced S phase cell cycle arrest in MCF-7 and LCC2 cells [1].
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| ln Vivo |
PROTAC AR Degrader-12 (Compound 18o) (5-10 μM/kg, intraperitoneal injection, every other day) significantly inhibited tumor growth in MCF-7 cells and LCC2 xenograft mice, promoted AR protein modification and ERα signaling inhibition, without causing weight loss or other toxicities [1].
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| Cell Assay |
Western Blot Analysis[1]
Cell Types: MCF-7 cells Tested Concentrations: 0.01 μM, 0.1 μM, 1 μM, 2 μM Incubation Duration: 0 h, 3 h, 6 h, 12 h, 18 h, 24 h Experimental Results: Effectively and in a dose-dependent manner degraded AR protein. Time-dependent effect on AR degradation. Caused a concentration-dependent downregulation of ERα protein. Real Time qPCR[1] Cell Types: MCF-7 cells Tested Concentrations: 0 μM, 1 μM, 5 μM Incubation Duration: 0 h, 4 h, 24 h Experimental Results: AR mRNA expression increased significantly with increasing concentration; ERα mRNA expression was downregulated. The expression of ERα target genes (TFF1, PGR) and AR target genes (PSA, TMPRSS2) was significantly suppressed after 24 hours. Significantly inhibited the mRNA expression of FOXA1, GREB1, SRC, and PELP1. |
| Animal Protocol |
Animal/Disease Models: Balb/c nude mice (female, 4 weeks old) were subcutaneously injected with MCF-7 human breast cancer cells (5 × 106 cells)[1].
Doses: 5 μM/kg, 10 μM/kg Route of Administration: I.p., once every other day Experimental Results: At a dose of 10 μM/kg, it significantly inhibited tumor growth. Tumor volume decreased, and Ki67 proliferation marker expression was reduced. AR and ERα protein levels were downregulated in tumor tissue. No significant change in body weight or significant toxicity was observed. Animal/Disease Models: Balb/c nude mice (female, 4 weeks old) were subcutaneously injected with tamoxifen-resistant LCC2 human breast cancer cells (5 × 106 cells)[1]. Doses: 5 μM/kg, 10 μM/kg Route of Administration: I.p., once every other day Experimental Results: Tumor growth inhibition rate (TGI) reached 58% at a dose of 10 μM/kg. Ki67 expression was decreased, and AR and ERα proteins were downregulated. Body weight remained stable, with no signs of toxicity. |
| References |
| Molecular Formula |
C57H76N8O10S
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|---|---|
| Molecular Weight |
1065.33
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| Appearance |
Typically exists as solids at room temperature
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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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.9387 mL | 4.6934 mL | 9.3868 mL | |
| 5 mM | 0.1877 mL | 0.9387 mL | 1.8774 mL | |
| 10 mM | 0.0939 mL | 0.4693 mL | 0.9387 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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