| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
| Targets |
PROTAC CYP1B1 degrader-1 targets CYP1B1 for ubiquitination and proteasomal degradation. It shows potent inhibitory activity against CYP1B1 (IC50 = 95.1 nM) with high selectivity over CYP1A2 (IC50 = 9838.6 nM), minimizing off-target effects on other CYP isoforms. It is designed to eliminate CYP1B1-mediated drug resistance.
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|---|---|
| ln Vitro |
In cell-free CYP inhibition assays, PROTAC CYP1B1 degrader-1 inhibits CYP1B1 with an IC50 of 95.1 nM. In cells, it acts as a PROTAC, recruiting an E3 ubiquitin ligase (via the cereblon ligand pomalidomide) to CYP1B1, leading to CYP1B1 ubiquitination and subsequent degradation by the 26S proteasome. This restores chemosensitivity to drugs inactivated by CYP1B1.
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| ln Vivo |
In vivo, PROTAC CYP1B1 degrader-1 has been studied in prostate cancer models characterized by CYP1B1 overexpression. By inducing sustained CYP1B1 degradation, the compound potentially reverses CYP1B1-mediated resistance to chemotherapeutics, enhancing antitumor efficacy. Detailed dosing information requires additional literature review.
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| Enzyme Assay |
The cell-free CYP inhibition assay is performed using recombinant human CYP1B1 enzyme, a fluorescent substrate, and an NADPH-regenerating system. Varying concentrations of PROTAC CYP1B1 degrader-1 (0.1 nM-100 uM) are added. After incubation at 37degC for 30-60 min, metabolite fluorescence (e.g., resorufin) is measured. For ternary complex formation, the compound can be incubated with purified CYP1B1 and cereblon, and complex formation can be assessed by SPR or AlphaScreen.
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| Cell Assay |
CYP1B1-overexpressing prostate cancer cells are seeded in 96-well plates. Cells are treated with PROTAC CYP1B1 degrader-1 (0.1-10 uM) for 6-48 hours. CYP1B1 protein levels are quantified by Western blot. Cells are then treated with chemotherapeutic agents (e.g., docetaxel) for 72-96 hours, and cell viability is measured by MTT or CellTiter-Glo to assess resensitization. Apoptosis is measured by caspase-3/7 activation or Annexin V staining.
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| Animal Protocol |
In mouse xenograft models of CYP1B1-overexpressing prostate cancer, PROTAC CYP1B1 degrader-1 is likely administered via intraperitoneal or intravenous injection at doses ranging from 10-50 mg/kg, daily or every other day, for 2-4 weeks. Tumor volume is measured by calipers. Post-treatment, tumors are harvested for CYP1B1 protein analysis (Western blot) and apoptosis markers.
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| ADME/Pharmacokinetics |
PK data are limited. Molecular weight: 785.80; formula: C43H39N5O10. Solubility: DMF (10 mg/mL). Storage: powder at -20degC for 3 years, protect from light; in solvent at -80degC for 6 months. The compound contains a cereblon ligand (pomalidomide), a linker, and a CYP1B1 binding moiety (alpha-naphthoflavone).
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| Toxicity/Toxicokinetics |
Standard safety precautions for PROTAC molecules apply. PROTAC CYP1B1 degrader-1 is for research use only, not for human therapy. Avoid inhalation and contact. Use personal protective equipment and work in a well-ventilated area.
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| Additional Infomation |
This is a research-grade PROTAC, not an approved drug. It is used to study the role of CYP1B1 in drug resistance and cancer. It is a useful chemical probe for selective CYP1B1 degradation. Purity: ≥98%. Also known as alpha-naphthoflavone-based CYP1B1 degrader.
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| Molecular Formula |
C43H39N5O10
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|---|---|
| Molecular Weight |
785.79727101326
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| Exact Mass |
785.269
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| CAS # |
2411389-67-6
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| PubChem CID |
162657232
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
5
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
12
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| Rotatable Bond Count |
14
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| Heavy Atom Count |
58
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| Complexity |
1570
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1(=O)C2=C(C(OCCCCCCN3C=C(C4=CC=C(C5OC6=C7C(C(OC)=CC=C7OC)=C(OC)C=C6C(=O)C=5)C=C4)N=N3)=CC=C2)C(=O)N1C1CCC(=O)NC1=O
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| InChi Key |
MRMQVUIZIOZVSD-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C43H39N5O10/c1-54-31-16-17-32(55-2)39-38(31)35(56-3)21-27-30(49)22-34(58-40(27)39)25-13-11-24(12-14-25)28-23-47(46-45-28)19-6-4-5-7-20-57-33-10-8-9-26-37(33)43(53)48(42(26)52)29-15-18-36(50)44-41(29)51/h8-14,16-17,21-23,29H,4-7,15,18-20H2,1-3H3,(H,44,50,51)
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| Chemical Name |
2-(2,6-dioxopiperidin-3-yl)-4-[6-[4-[4-(6,7,10-trimethoxy-4-oxobenzo[h]chromen-2-yl)phenyl]triazol-1-yl]hexoxy]isoindole-1,3-dione
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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: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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) |
DMF : 10 mg/mL (~12.73 mM)
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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 | 1.2726 mL | 6.3629 mL | 12.7259 mL | |
| 5 mM | 0.2545 mL | 1.2726 mL | 2.5452 mL | |
| 10 mM | 0.1273 mL | 0.6363 mL | 1.2726 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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