| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
| Targets |
PROTAC RAR Degrader-1 targets retinoic acid receptors (RARs), nuclear receptors that are activated by retinoic acid and play critical roles in development, differentiation, and cancer. RARs are transcription factors that regulate the expression of genes involved in cell growth, differentiation, and apoptosis. The compound uses PROTAC technology to recruit RAR to an E3 ubiquitin ligase (cIAP1), inducing its ubiquitination and subsequent proteasomal degradation. The compound consists of a RAR ligand binding group, a linker, and a cIAP1 ligand binding group. By degrading RAR, the compound reduces RAR levels and inhibits RAR-mediated signaling pathways.
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| ln Vitro |
PROTAC RAR Degrader-1 demonstrates potent in vitro activity in degrading RAR. In HT1080 cells, the compound reduces RAR levels, reaching maximum degradation at a concentration of 30 microM. The compound's activity is concentration-dependent, with degradation observed at appropriate concentrations. As a PROTAC (SNIPER), the compound induces the ubiquitination and degradation of RAR through the recruitment of the cIAP1 E3 ubiquitin ligase. The compound's ability to degrade RAR makes it a valuable tool for studying RAR biology and evaluating RAR degradation as a therapeutic strategy. Comprehensive in vitro activity data are available from research publications.
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| ln Vivo |
In vivo activity of PROTAC RAR Degrader-1 has not been extensively characterized in the public domain. As an RAR degrader, the compound would be expected to have effects on cell differentiation and proliferation. RAR modulators have been studied in various animal models of cancer and other diseases. However, comprehensive in vivo efficacy studies using PROTAC RAR Degrader-1 specifically have not been widely published. The compound is primarily used as a research tool for in vitro studies of RAR degradation. Further research is needed to determine the in vivo activity of this compound.
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| Cell Assay |
In vitro cellular assays for PROTAC RAR Degrader-1 are performed using RAR-expressing cell lines such as HT1080 fibrosarcoma cells. Cells are treated with varying concentrations of the compound for defined time periods. RAR protein levels are assessed by Western blot using RAR-specific antibodies. Maximum degradation is observed at 30 microM. RAR target gene expression is measured by qRT-PCR. Cell proliferation and viability are assessed using MTT or CellTiter-Glo assays. Cell differentiation can be assessed by measuring differentiation markers. Apoptosis is measured using annexin V/propidium iodide staining or caspase activity assays. Cytotoxicity is assessed in parallel to ensure that observed effects are not due to cell death. Degradation efficacy is expressed as percent reduction in RAR levels compared to vehicle-treated controls.
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| Animal Protocol |
In vivo animal studies for PROTAC RAR Degrader-1 have not been extensively reported in the public domain. As an RAR degrader, the compound could potentially be evaluated in mouse xenograft models of cancer or other disease models where RAR plays a role. In such studies, the compound would be administered via intraperitoneal injection or oral gavage, and endpoints would include tumor growth, RAR degradation in tumor tissues, and biomarker analysis. However, comprehensive in vivo efficacy studies have not been widely published. The compound is primarily used as a research tool for in vitro studies.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of PROTAC RAR Degrader-1 have not been extensively characterized in the public domain. The compound has a molecular formula of C51H72N4O11 and a molecular weight of 917.14 g/mol. Its chemical name is 2-(3-{2-[2-(2-{2-[(2S)-2-[(2S,3R)-3-amino-2-hydroxy-4-phenylbutanamido]-4-methylpentanamido]ethoxy}ethoxy)ethoxy]acetamido}propoxy)-4-[(1E)-3-(3,5-di-tert-butylphenyl)-3-oxoprop-1-en-1-yl]benzoic acid. As a PROTAC with a relatively large molecular weight, the compound would be expected to have limited oral bioavailability. Comprehensive pharmacokinetic parameters have not been reported.
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| Toxicity/Toxicokinetics |
PROTAC RAR Degrader-1 is intended for laboratory research use only and has not undergone comprehensive toxicology testing. As a compound that induces protein degradation, the compound would be expected to have effects on RAR signaling and cell differentiation. Standard in vitro cytotoxicity assays in cell lines are typically performed alongside efficacy studies to rule out nonspecific toxicity. In vivo, animals would be monitored for signs of toxicity if the compound were to be evaluated in animal studies. Comprehensive toxicological characterization including genotoxicity and repeated-dose toxicity studies has not been reported. The compound is not approved for human use and is strictly intended for research purposes.
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| References | |
| Additional Infomation |
PROTAC RAR Degrader-1 is a PROTAC (SNIPER) that degrades retinoic acid receptors (RARs) by recruiting cIAP1 E3 ligase. It achieves maximum RAR degradation at 30 microM in HT1080 cells. The compound has a molecular formula of C51H72N4O11 and a molecular weight of 917.14 g/mol. PROTAC RAR Degrader-1 has not entered clinical trials and is available for research purposes only.
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| Molecular Formula |
C51H72N4O11
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|---|---|
| Molecular Weight |
917.137595176697
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| Exact Mass |
916.52
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| CAS # |
1351169-27-1
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| PubChem CID |
54764325
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| Appearance |
White to off-white solid powder
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| LogP |
7.261
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| Hydrogen Bond Donor Count |
6
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| Hydrogen Bond Acceptor Count |
12
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| Rotatable Bond Count |
30
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| Heavy Atom Count |
66
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| Complexity |
1480
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| Defined Atom Stereocenter Count |
3
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| SMILES |
CC(C)C[C@@H](C(=O)NCCOCCOCCOCC(=O)NCCCOC1=C(C=CC(=C1)/C=C/C(=O)C2=CC(=CC(=C2)C(C)(C)C)C(C)(C)C)C(=O)O)NC(=O)[C@H]([C@@H](CC3=CC=CC=C3)N)O
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| InChi Key |
ZAOSGDCLGNWLSI-ACALULJJSA-N
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| InChi Code |
InChI=1S/C51H72N4O11/c1-34(2)27-42(55-48(60)46(58)41(52)28-35-13-10-9-11-14-35)47(59)54-20-22-63-23-24-64-25-26-65-33-45(57)53-19-12-21-66-44-29-36(15-17-40(44)49(61)62)16-18-43(56)37-30-38(50(3,4)5)32-39(31-37)51(6,7)8/h9-11,13-18,29-32,34,41-42,46,58H,12,19-28,33,52H2,1-8H3,(H,53,57)(H,54,59)(H,55,60)(H,61,62)/b18-16+/t41-,42+,46+/m1/s1
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| Chemical Name |
2-[3-[[2-[2-[2-[2-[[(2S)-2-[[(2S,3R)-3-amino-2-hydroxy-4-phenylbutanoyl]amino]-4-methylpentanoyl]amino]ethoxy]ethoxy]ethoxy]acetyl]amino]propoxy]-4-[(E)-3-(3,5-ditert-butylphenyl)-3-oxoprop-1-enyl]benzoic acid
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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: 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 : ≥ 80 mg/mL (~87.23 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2 mg/mL (2.18 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 20.0 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. Solubility in Formulation 2: ≥ 2 mg/mL (2.18 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 20.0 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. View More
Solubility in Formulation 3: ≥ 2 mg/mL (2.18 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 | 1.0903 mL | 5.4517 mL | 10.9035 mL | |
| 5 mM | 0.2181 mL | 1.0903 mL | 2.1807 mL | |
| 10 mM | 0.1090 mL | 0.5452 mL | 1.0903 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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