| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 100mg | |||
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| Targets |
Carotegrast's primary target is the α4 integrin receptor, a cell surface protein involved in leukocyte trafficking. Integrins are heterodimeric proteins that mediate cell-cell and cell-extracellular matrix adhesion. The α4 subunit can pair with either β1 (forming VLA-4) or β7 (forming LPAM-1). Both of these integrins play critical roles in the migration of lymphocytes to sites of inflammation. By inhibiting this receptor, Carotegrast blocks the adhesion and extravasation of inflammatory cells, thereby reducing tissue inflammation.
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| ln Vitro |
Carotegrast is an orally available α4 integrin receptor inhibitor. In vitro studies confirm its ability to bind to the α4 integrin receptor and block its function. The compound is typically dissolved in DMSO for in vitro assays, with a solubility of 100 mg/mL. Its anti-inflammatory activity is attributed to its capacity to inhibit the interaction between integrins on immune cells and their adhesion molecules on endothelial cells, thereby preventing the infiltration of these cells into inflamed tissues.
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| ln Vivo |
Carotegrast has been studied in vivo for its anti-inflammatory effects. As an orally active compound, it is administered to animal models of inflammatory diseases to assess its efficacy. These studies are designed to evaluate its ability to reduce inflammation and tissue damage in conditions like ulcerative colitis. The compound's in vivo activity stems from its systemic inhibition of α4 integrin, which reduces the recruitment of leukocytes to sites of inflammation.
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| Enzyme Assay |
The in vitro activity of Carotegrast is determined using cell-based adhesion assays. In a typical protocol, cells expressing α4 integrins are pre-incubated with varying concentrations of Carotegrast. These cells are then added to plates coated with its ligands, such as VCAM-1 or MAdCAM-1. After washing away non-adherent cells, the number of bound cells is quantified. The concentration of Carotegrast that inhibits 50% of cell adhesion (IC50) is then calculated, providing a direct measure of its receptor-blocking activity.
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| Cell Assay |
Cellular assays for Carotegrast typically involve studying its effect on immune cell adhesion and migration. One common protocol involves using a human T-cell line or primary lymphocytes. The cells are treated with Carotegrast and then stimulated with chemokines. Their ability to adhere to immobilized VCAM-1 or to migrate through an endothelial cell monolayer is then measured. These assays are performed in a 96-well plate format, and the results demonstrate the compound's ability to functionally block α4 integrin-mediated cellular processes.
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| Animal Protocol |
The in vivo efficacy of Carotegrast is evaluated in animal models of inflammatory bowel disease, such as the dextran sulfate sodium (DSS)-induced colitis model in mice. In these studies, Carotegrast is administered orally once or twice daily. Disease activity is monitored by assessing weight loss, stool consistency, and the presence of blood in the stool. At the end of the study, the colon is harvested and assessed for histological signs of inflammation, and the number of infiltrating immune cells is quantified.
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| ADME/Pharmacokinetics |
Dosing is typically oral, and the compound is formulated in a suitable vehicle for administration. For pharmacokinetic studies, the compound is administered to animals (e.g., rats or dogs) via oral gavage. Blood samples are collected at various time points, and plasma concentrations of Carotegrast are measured. Key parameters such as Cmax, Tmax, half-life, and oral bioavailability are calculated. The compound has a molecular weight of 555.41 and is soluble in DMSO, which informs its formulation for in vivo studies.
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| Toxicity/Toxicokinetics |
The safety and tolerability of Carotegrast are assessed in standard toxicology studies. In these studies, the compound is administered to rodents and non-rodents at various dose levels for a set period (e.g., 28 days or 3 months). Parameters such as body weight, food consumption, clinical observations, clinical pathology (hematology, serum chemistry), and histopathology are evaluated. The goal is to determine the No-Observed-Adverse-Effect Level (NOAEL) and identify any potential target organs of toxicity.
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| References | |
| Additional Infomation |
Carotegrast is an oral α4 integrin receptor inhibitor with potential applications in treating inflammatory diseases such as ulcerative colitis. It is also known by the name HCA2969. As a research compound, it is not approved for clinical use but represents a therapeutic strategy of blocking leukocyte trafficking to reduce inflammation. Its mechanism of action is analogous to that of other α4 integrin inhibitors, such as vedolizumab and natalizumab, but as a small molecule, it offers the advantage of oral administration.
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| Molecular Formula |
C27H24N4O5CL2
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|---|---|
| Molecular Weight |
555.40926
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| Exact Mass |
554.112
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| CAS # |
401904-75-4
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| Related CAS # |
Carotegrast methyl;401905-67-7
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| PubChem CID |
10120218
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| Appearance |
White to light yellow solid powder
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| LogP |
4.062
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
38
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| Complexity |
902
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CN1C2=C(C=C(C=C2)N(C)C)C(=O)N(C1=O)C3=CC=C(C=C3)C[C@@H](C(=O)O)NC(=O)C4=C(C=CC=C4Cl)Cl
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| InChi Key |
YQKBOUPIOWUMTE-NRFANRHFSA-N
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| InChi Code |
InChI=1S/C27H24Cl2N4O5/c1-31(2)17-11-12-22-18(14-17)25(35)33(27(38)32(22)3)16-9-7-15(8-10-16)13-21(26(36)37)30-24(34)23-19(28)5-4-6-20(23)29/h4-12,14,21H,13H2,1-3H3,(H,30,34)(H,36,37)/t21-/m0/s1
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| Chemical Name |
(2S)-2-[(2,6-dichlorobenzoyl)amino]-3-[4-[6-(dimethylamino)-1-methyl-2,4-dioxoquinazolin-3-yl]phenyl]propanoic 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 |
| 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 : ~100 mg/mL (~180.05 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 | 1.8005 mL | 9.0024 mL | 18.0047 mL | |
| 5 mM | 0.3601 mL | 1.8005 mL | 3.6009 mL | |
| 10 mM | 0.1800 mL | 0.9002 mL | 1.8005 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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