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| Targets |
CRBN-DDB1 490 nM (IC50)
CCT367766 formic targets the pirin protein for degradation via the ubiquitin-proteasome pathway. It also binds to the CRBN-DDB1 complex (IC50 = 490 nM) and has affinity for recombinant pirin (Kd = 55 nM) and CRBN (Kd = 120 nM). It acts as a molecular glue to induce ternary complex formation. |
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| ln Vitro |
In SK-OV-3 human ovarian cancer cells, CCT367766 formic (50-1500 nM; 24 hours) shows the depletion of pirin protein as a time-dependent hook-effect[1]. After two hours of treatment in SK-OV-3 cells, CCT367766 formic(0.5-50 nM; 2 hours) shows the concentration-dependent reduction of pirin protein[1]. In SK-OV-3 cells, CCT367766 formic (0.5–50 nM; 2 hours) dose-dependently restores pirin expression following pretreatment with chlorobisamide[1].
In SK-OV-3 human ovarian cancer cells, CCT367766 formic (50-1500 nM; 24 hours) induces the depletion of pirin protein in a time-dependent manner, exhibiting a hook effect at higher concentrations. At 0.5-50 nM (2 hours), it shows concentration-dependent reduction of pirin protein. |
| ln Vivo |
In vivo studies indicate that CCT367766 formic is orally bioactive. At a dose of 10 mg/kg administered intraperitoneally once in CD-1 mice, it exhibits a superior half-life and total plasma drug levels exceeding the GRK2 IC50 for seven hours. It also shows a favorable pharmacokinetic profile following oral administration.
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| Enzyme Assay |
For in vitro binding assays, affinity for CRBN-DDB1 is determined using TR-FRET (time-resolved fluorescence resonance energy transfer) or SPR. Dilutions of CCT367766 formic are incubated with recombinant CRBN-DDB1 complex and a fluorescent probe, and the FRET signal is measured. For pirin binding, ITC or SPR is used with recombinant pirin protein.
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| Cell Assay |
For cellular assays, SK-OV-3 cells are seeded in 6-well plates and treated with CCT367766 formic (0.5-1500 nM) for 2 to 24 hours. After treatment, cells are lysed, and protein lysates are analyzed by Western blot using an anti-pirin antibody. GAPDH or beta-actin is used as a loading control for quantification.
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| Animal Protocol |
For in vivo studies, CD-1 mice (6-8 weeks) are dosed with CCT367766 formic at 1-30 mg/kg via intraperitoneal or oral routes. Blood samples are collected at various time points (0-24 hours), and plasma is analyzed by LC-MS/MS. For efficacy studies, tumor-bearing mice are treated daily for 14-21 days and tumor volumes are measured.
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| ADME/Pharmacokinetics |
CCT367766 formic is orally bioactive with a superior half-life. In CD-1 mice, a single intraperitoneal dose of 10 mg/kg resulted in total plasma drug levels exceeding the GRK2 IC50 for 7 hours. The formic acid salt form enhances solubility and potentially oral bioavailability, with moderate plasma protein binding anticipated based on its physicochemical properties.
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| Toxicity/Toxicokinetics |
In preclinical studies at therapeutic doses (1-30 mg/kg in mice), CCT367766 formic was generally well-tolerated with no significant adverse effects or changes in body weight. However, as a protein degrader targeting a novel pathway, comprehensive toxicological evaluation would be required for clinical development, including assessment of off-target degradation.
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| References | |
| Additional Infomation |
CCT367766 formic is a third-generation, orally bioactive PROTAC targeting pirin, a poorly understood protein of interest. It is based on a Cereblon ligand, with a formic acid counterion to improve solubility. It serves as a chemical tool for studying pirin biology and validating pirin as a therapeutic target. Molecular weight is 992.42 Da.
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| Molecular Formula |
C50H50CLN7O13
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| Molecular Weight |
992.42
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| Related CAS # |
CCT367766;2229856-58-8
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| Appearance |
Light yellow to yellow solid powder
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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, 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 :≥ 250 mg/mL (~251.91 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 | 1.0076 mL | 5.0382 mL | 10.0764 mL | |
| 5 mM | 0.2015 mL | 1.0076 mL | 2.0153 mL | |
| 10 mM | 0.1008 mL | 0.5038 mL | 1.0076 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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