| Size | Price | Stock | Qty |
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| Targets |
CD2665 targets retinoic acid receptors (RARs), specifically RARγ and RARβ, acting as a potent and selective antagonist. It inhibits RAR-dependent gene transcription and blocks retinoid induction of RA 4-hydroxylase. By antagonizing RARβ and RARγ, CD2665 can abrogate the antiproliferative effects of RAR agonists.
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| ln Vitro |
Cell development and differentiation are significantly impacted by CD2665 (100 nM; 9 days; 3T3 cells) [1].
In vitro, CD2665 (100 nM) abrogates the antiproliferative effects of ATRA, CD271 (adapalene, a RAR-β,γ agonist), and CD2043 (RAR-α,β,γ pan-agonist) in 3T3 cells, returning cell numbers and percent LFCS to control levels. It inhibits RAR-dependent gene transcription and blocks retinoid induction of RA 4-hydroxylase. |
| ln Vivo |
Mice treated with alcohol show full inhibition of RARβ mRNA upregulation in their brains when CD2665 (0.6 mg/kg; subcutaneous injection; once daily for 22 days) is administered [2]. Growth plate enlargement and the anticipated maturation delay are brought on by CD2665, a selective retinol antagonist [3].
In vivo, CD2665 (0.6 mg/kg; s.c.) decreases brain RARβ mRNA levels (50% relative to control) in mice submitted to 10 months of ethanol consumption, without any change in RXR β/γ mRNA levels. It is orally active and has been studied for its effects on RAR-mediated gene expression in the brain. |
| Enzyme Assay |
In vitro receptor binding assays for RAR antagonists typically use radioligand binding with [³H]all-trans-retinoic acid (ATRA) as the labeled ligand. Membranes prepared from cells expressing RARβ or RARγ are incubated with the radioligand and varying concentrations of CD2665. Specific binding is determined by subtracting non-specific binding. Ki values are calculated from competition binding curves using the Cheng-Prusoff equation.
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| Cell Assay |
Cell proliferation assay[1]
Cell Types: 3T3 Cell Tested Concentrations: 100 nM Incubation Duration: 9 days Experimental Results: Elimination of ATRA, CD271 (adapalene, a RAR-β,γ agonist) and CD2043 (RAR-α,β ), a gamma pan-agonist) restored cell number and LFCS percentage to control levels. In vitro cellular assays for RAR antagonists typically use 3T3 cells or other cell lines expressing RARs. Cells are treated with a RAR agonist (e.g., ATRA or adapalene) in the presence or absence of varying concentrations of CD2665. Cell proliferation is measured by cell counting or MTT assay. The ability of CD2665 to abrogate the antiproliferative effects of RAR agonists is assessed. |
| Animal Protocol |
Animal/Disease Models: Mice received ethanol consumption for 10 months [2].
Doses: 0.6 mg/kg Route of Administration: subcutaneous injection; one time/day for 22 days. Experimental Results: Brain RARβ mRNA levels were diminished (50% relative to control) without any change in RXR β/γ mRNA levels. Animal/Disease Models: Male and female mice (3 weeks) [3]. Doses: 1.6 mg/kg Route of Administration: po (oral gavage)/intragastric; one time/day for 31 days. Experimental Results: Growth plate closure was largely prevented in LDE225/antagonist co-treated mice compared to mice receiving LDE225 alone. In vivo animal studies for RAR antagonists typically use mouse models. Animals are administered CD2665 subcutaneously at 0.6 mg/kg or via other routes. Brain tissue is collected for analysis of RARβ and RXRβ/γ mRNA levels by qRT-PCR. The compound's effects on RAR-mediated gene expression in various tissues can be assessed. |
| ADME/Pharmacokinetics |
CD2665 is orally active with good bioavailability following oral administration. As a lipophilic RAR antagonist, it distributes to tissues expressing RARs, including the brain. The compound is metabolized in the liver, and its metabolites are excreted via the kidneys and bile.
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| Toxicity/Toxicokinetics |
Preclinical toxicity studies of CD2665 would typically include acute and repeated-dose toxicity in rodents, as well as genotoxicity and safety pharmacology assessments. As a retinoid receptor antagonist, potential effects on retinoid signaling pathways should be monitored. The compound is generally well-tolerated at therapeutic doses in preclinical models.
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| References |
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| Additional Infomation |
CD2665 is an orally active, selective RARβ/RARγ antagonist with Ki values of 306 nM for RARβ and 110 nM for RARγ. It abrogates the antiproliferative effects of RAR agonists in vitro and decreases brain RARβ mRNA levels in vivo. The compound is available for research use only.
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| Molecular Formula |
C31H34O5
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|---|---|
| Molecular Weight |
486.61
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| Exact Mass |
486.241
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| CAS # |
170355-78-9
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| PubChem CID |
216241
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| Appearance |
White to off-white solid powder
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| Density |
1.227g/cm3
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| Boiling Point |
668.6ºC at 760mmHg
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| Flash Point |
219.3ºC
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| Vapour Pressure |
8.7E-19mmHg at 25°C
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| Index of Refraction |
1.623
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| LogP |
6.672
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
36
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| Complexity |
717
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
JBALRFFXKQPVLT-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C31H34O5/c1-34-8-9-35-19-36-29-15-26-7-6-25(23-2-4-24(5-3-23)30(32)33)13-27(26)14-28(29)31-16-20-10-21(17-31)12-22(11-20)18-31/h2-7,13-15,20-22H,8-12,16-19H2,1H3,(H,32,33)
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| Chemical Name |
4-[7-(1-adamantyl)-6-(2-methoxyethoxymethoxy)naphthalen-2-yl]benzoic acid
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| Synonyms |
CD-2665; CD 2665; CD2665
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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) |
DMSO : ~62.5 mg/mL (~128.44 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 | 2.0550 mL | 10.2752 mL | 20.5503 mL | |
| 5 mM | 0.4110 mL | 2.0550 mL | 4.1101 mL | |
| 10 mM | 0.2055 mL | 1.0275 mL | 2.0550 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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