| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| Targets |
Carotegrast methyl targets the α4 integrin receptor, specifically the α4β1 and α4β7 complexes. Its bioactive metabolite, HCA2969, is a specific dual antagonist of these integrins. By blocking these integrins, it prevents the adhesion and migration of leukocytes to sites of inflammation.
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| ln Vitro |
In Jurkat, RPMI-8866, and TK-1 cell lines, HCA2969 inhibits human α4β1 integrin (KD=0.32 nM; IC50=5.8 nM), human α4β7 integrin (KD=0.46 nM; IC50=1.4 nM), and mouse α4β7 integrin (KD=0.2 nM; IC50=26 nM).
In vitro, Carotegrast methyl acts as an antagonist of the α4 integrin receptor. Its activity is typically measured in cell adhesion assays, where it blocks the binding of cells expressing α4 integrins to their ligands, such as VCAM-1 or MAdCAM-1. |
| ln Vivo |
In a mouse model, carotegrastmethyl (AJM300; sidewall; 0.03-1%; for 15 days) inhibits humiditis caused by the transfer of CD4+ T cells lacking in IL-10 [1]. In BALB/c mice (8-week-old female mice), carotenegrastmethyl (facial; 0.3, 3, 30, or 30 mg/kg; single sidewall) inhibits phase homing to Peyer's nest and raises peripheral count count[1].
In vivo, Carotegrast methyl prevents the development of colitis in mice. This demonstrates its efficacy in an animal model of inflammatory bowel disease, supporting its potential for treating ulcerative colitis and Crohn's disease. |
| Enzyme Assay |
In vitro receptor binding assays measure the affinity of Carotegrast methyl (or its active metabolite HCA2969) for the α4 integrin receptor. This is typically performed using competition binding experiments with a radiolabeled ligand on cells expressing the receptor.
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| Cell Assay |
In vitro cell-based assays evaluate the functional antagonism of the compound. This is done using cell adhesion assays, where cells expressing α4 integrins are allowed to adhere to immobilized ligands (e.g., VCAM-1) in the presence of the compound. Inhibition of adhesion indicates antagonist activity.
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| Animal Protocol |
Animal/Disease Models: Mouse colitis model induced by adoptive transfer of IL-10-deficient CD4+ T cells [1] 0.03, 0.1, 0.3 or 1% Dosing: for 15 days
Experimental Results: Histological improvement of epithelial cell proliferation, inflammatory cells diminished infiltration and diminished mucus production. Prevents the increase in colon weight in a model of colitis induced by adoptive transfer of CD4+CD45RBhigh T cells. The in vivo efficacy of Carotegrast methyl is evaluated in mouse models of colitis, such as the DSS-induced colitis model. The compound is administered orally, and disease severity is assessed by measuring body weight loss, colon length, and histological scores of inflammation. |
| ADME/Pharmacokinetics |
Carotegrast methyl is an orally bioavailable small molecule. Its pharmacokinetic properties support once- or twice-daily oral dosing. The active metabolite, HCA2969, is responsible for the pharmacological activity in vivo.
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| Toxicity/Toxicokinetics |
The toxicological profile of Carotegrast methyl has been evaluated in preclinical studies. As an integrin antagonist that modulates immune cell trafficking, potential side effects may include increased susceptibility to infections. Its safety in humans has been assessed in clinical trials.
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| References | |
| Additional Infomation |
Carroteglast methyl ester is being investigated in the clinical trial NCT03531892 (a study evaluating the safety and efficacy of AJM300 in patients with active ulcerative colitis).
Carotegrast methyl (AJM300) has been investigated in clinical trials for the treatment of ulcerative colitis. It is a novel, orally available integrin antagonist that offers a potential alternative to biologic therapies, which are typically administered by injection or infusion. |
| Molecular Formula |
C28H26CL2N4O5
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|---|---|
| Molecular Weight |
569.435844898224
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| Exact Mass |
568.128
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| Elemental Analysis |
C, 59.06; H, 4.60; Cl, 12.45; N, 9.84; O, 14.05
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| CAS # |
401905-67-7
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| Related CAS # |
Carotegrast;401904-75-4
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| PubChem CID |
9872780
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
4.151
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
39
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| Complexity |
918
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| Defined Atom Stereocenter Count |
1
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| SMILES |
ClC1C=CC=C(C=1C(N[C@H](C(=O)OC)CC1C=CC(=CC=1)N1C(N(C)C2C=CC(=CC=2C1=O)N(C)C)=O)=O)Cl
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| InChi Key |
MMHHPKCJJIFLBQ-QFIPXVFZSA-N
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| InChi Code |
InChI=1S/C28H26Cl2N4O5/c1-32(2)18-12-13-23-19(15-18)26(36)34(28(38)33(23)3)17-10-8-16(9-11-17)14-22(27(37)39-4)31-25(35)24-20(29)6-5-7-21(24)30/h5-13,15,22H,14H2,1-4H3,(H,31,35)/t22-/m0/s1
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| Chemical Name |
methyl (2S)-2-[(2,6-dichlorobenzoyl)amino]-3-[4-[6-(dimethylamino)-1-methyl-2,4-dioxoquinazolin-3-yl]phenyl]propanoate
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| Synonyms |
Carotegrast methyl; AJM300; AJM-300; AJM 300; PTC-100, PTC100; PTG 100;
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| HS Tariff Code |
2934.99.03.00
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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 (~175.61 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 1.25 mg/mL (2.20 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 12.5 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: 1.25 mg/mL (2.20 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 12.5 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7561 mL | 8.7806 mL | 17.5611 mL | |
| 5 mM | 0.3512 mL | 1.7561 mL | 3.5122 mL | |
| 10 mM | 0.1756 mL | 0.8781 mL | 1.7561 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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