| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| ln Vitro |
AR Degrader-3 (Compound A6) (0.2-5 μM, 24 h) broadly inhibited the transcriptional activity of AR by dose-dependently inhibiting the expression of exogenous and endogenous AR in PC-3 and C4-2 cells; in addition, it significantly inhibited the expression of endogenous AR and ARV7 in Enzalutamide-resistant 22Rv1 cells and inhibited the transcriptional activity of AR mutants (W741L, T877A, F876L) in PC-3 cells[1]. AR Degrader-3 (0.078-10 μM, 0-36 h) inhibited the protein level of ARV7 in 22Rv1 cells (DC50 = 0.24 μM) in a dose-dependent manner, significantly downregulated the protein level of AR in C4-2 cells (DC50 = 0.18 μM), and downregulated the protein level of ARV7 in a time-dependent manner[1]. AR Degrader-3 can effectively inhibit AR and ARV7 in LNCaP cells. The mechanism is through direct binding of AR-LBD (IC50 = 105.4 nM) and AR-AF1 (KD = 23.0 μM)[1]. AR Degrader-3 (1-5 μM, 4-8 h) degrades AR and ARV7 via the ubiquitin-proteasome pathway (UPP). In C4-2 and 22Rv1 cells, AR Degrader-3 dose-dependently reduces the protein levels (but not the mRNA levels) of AR and ARV7, respectively. Cycloheximide treatment can accelerate the degradation of AR and ARV7. MG132 can antagonize the protein reduction effect of AR Degrader-3. AR Degrader-3 also significantly induces the ubiquitination of AR[1]. AR Degrader-3 (72 h) inhibited the proliferation of C4-2 cells (IC50 = 0.59 μM) and 22Rv1 cells (IC50 = 1.4 μM), but had little effect on DU145 cells (IC50 > 50 μM) and PC-3 cells (IC50 = 48.6 μM) [1]. AR Degrader-3 (0.2–5 μM, 8–24 h) blocked R1881-induced PSA protein expression in a dose-dependent manner and reduced the mRNA levels of PSA and PMEPA1 in 22Rv1 cells [1]. AR Degrader-3 (1–2 μM, 14 days) selectively reduced the number of colonies formed in 22Rv1 cells, but had no effect on the number of colonies formed in AR-negative PC-3 cells and promoted apoptosis in 22Rv1 cells [1].
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|---|---|
| ln Vivo |
AR Degrader-3 (Compound A6) (15-30 mg/kg, lateral wall, once daily for 14 days) effectively inhibited the growth of CRPC tumors in 22Rv1 cell-bearing mice without significant toxicity [1].
|
| Cell Assay |
Western Blot Analysis[1]
Cell Types: 22Rv1 cells Tested Concentrations: 5 μM Incubation Duration: 24 h Experimental Results: Significantly downregulated the level of ARV7. Western Blot Analysis[1] Cell Types: 22Rv1 cells, C4-2 cells Tested Concentrations: 0.078 μM, 0.156 μM, 0.31 μM, 0.62 μM, 1.25 μM, 2.5 μM, 5 μM, 10 μM Incubation Duration: 24 h Experimental Results: Dose-dependently suppressed ARV7 (DC50 = 0.24 μM) protein level in 22Rv1 cells, down-regulated AR (DC50 = 0.18 μM) protein level in C4-2 cells. Western Blot Analysis[1] Cell Types: 22Rv1 cells Tested Concentrations: 0.2 μM, 1 μM, 5 μM Incubation Duration: 24 h Experimental Results: Blocked R1881-induced PSA protein expression in a dose-dependent manner in 22Rv1 cells. RT-PCR[1] Cell Types: 22Rv1 cells Tested Concentrations: 0.2 μM, 1 μM, 5 μM Incubation Duration: 8 h Experimental Results: Reduced the mRNA level of PSA in 22Rv1 cells. RT-PCR[1] Cell Types: 22Rv1 cells Tested Concentrations: 0.2 μM, 1 μM, 5 μM Incubation Duration: 24 h Experimental Results: Reduced the mRNA level of PMEPA1 in 22Rv1 cells. Cell Proliferation Assay[1] Cell Types: 22Rv1 cells, PC-3 cells Tested Concentrations: 1 μM, 2 μM Incubation Duration: 14 days Experimental Results: Decreased 22Rv1 cells colony numbers but showed no influence on AR-negative PC-3 cells colony numbers. |
| Animal Protocol |
Animal/Disease Models: Male BALB/c nude mice (5-week-old) were subcutaneously inoculated with 5 × 106 22Rv1 cells[1].
Doses: 15 mg/kg, 30 mg/kg Route of Administration: P.o., once daily for 14 days Experimental Results: Suppressed 22Rv1 tumor progression. Showed no change in body weight. Significantly decreased AR levels in the tumor tissues. |
| References |
| Molecular Formula |
C23H21N3O4S
|
|---|---|
| Molecular Weight |
435.50
|
| Exact Mass |
435.125
|
| CAS # |
1182011-65-9
|
| PubChem CID |
36321319
|
| Appearance |
Typically exists as solids at room temperature
|
| Hydrogen Bond Donor Count |
1
|
| Rotatable Bond Count |
7
|
| Heavy Atom Count |
31
|
| Complexity |
581
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
CC1=C(C(=NO1)C)COC2=CC=C(C=C2)C(=O)NC3=NC(=CS3)C4=CC=C(C=C4)OC
|
| InChi Key |
QQDVQSAQUAHWDB-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C23H21N3O4S/c1-14-20(15(2)30-26-14)12-29-19-10-6-17(7-11-19)22(27)25-23-24-21(13-31-23)16-4-8-18(28-3)9-5-16/h4-11,13H,12H2,1-3H3,(H,24,25,27)
|
| Chemical Name |
4-[(3,5-dimethyl-1,2-oxazol-4-yl)methoxy]-N-[4-(4-methoxyphenyl)-1,3-thiazol-2-yl]benzamide
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| 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 | 2.2962 mL | 11.4811 mL | 22.9621 mL | |
| 5 mM | 0.4592 mL | 2.2962 mL | 4.5924 mL | |
| 10 mM | 0.2296 mL | 1.1481 mL | 2.2962 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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