| Identification | Back Directory | [Name]
Cositecan | [CAS]
401905-67-7 | [Synonyms]
AJM-300
RPMI-8866,HCA2969,Jurkat,inhibit,TK-1,colitis,AJM-300,Integrin,Inhibitor,Carotegrast methyl,orally,AJM 300
methyl (2S)-2-[(2,6-dichlorobenzoyl)amino]-3-[4-[6-(dimethylamino)-1-methyl-2,4-dioxoquinazolin-3-yl]phenyl]propanoate | [Molecular Formula]
C28H26Cl2N4O5 | [MDL Number]
MFCD34167496 | [MOL File]
401905-67-7.mol | [Molecular Weight]
569.44 |
| Chemical Properties | Back Directory | [density ]
1.382±0.06 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
DMSO : 100 mg/mL (175.61 mM; Need ultrasonic) | [form ]
Solid | [pka]
11.51±0.46(Predicted) | [color ]
Off-white to light yellow |
| Hazard Information | Back Directory | [Description]
Carotegrast methyl (trade name Carogra) is a small molecule α4-integrin antagonist being developed for the treatment of ulcerative colitis, a subtype of inflammatory bowel disease that affects millions of people in the United States and worldwide. In March 2022, Cartalast methyl was first approved in Japan for the treatment of patients with moderate ulcerative colitis who have had an inadequate response to 5-aminosalicylic acid. | [Uses]
Carotegrast methyl (AJM300) is an orally active and selective α4 integrin antagonist. HCA2969, an active metabolite of Carotegrast methyl, is a specific and dual α4β1/α4β7 integrin antagonist. Carotegrast methyl prevents the development of colitis in mice[1]. | [Mechanism of action]
Carotegrast methyl is a prodrug whose methyl ester functional group is hydrolyzed to the biologically active carboxylic acid form, which prevents the development of colitis by selectively inhibiting the binding of α4-integrin to cell adhesion molecules. Cartalast methyl reduces the migration of inflammatory cells to inflamed areas of the intestine by inhibiting α4-integrin, thereby alleviating symptoms. | [Synthesis]
According to the description in the patent applied by Ajinomoto Co., Inc., Carotegrast methyl can be assembled by polymerization by coupling Western aniline fragments and Eastern aniline fragments. | [in vivo]
Carotegrast methyl (AJM300; oral; 0.03-1%; for 15 days) prevents the development of colitis induced by transfer of IL-10 deficient CD4+ T cells in mice[1].
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Carotegrast methyl (oral; 0.3, 3, 30, or 30 mg/kg; a single oral) inhibits Lymphocyte homing to Peyer's patches and increases peripheral lymphocyte counts in a dose-dependent manner in BALB/c mice (8 weeks of age, female)[1].
| Animal Model: | Mouse model of colitis induced by adoptive transfer of IL-10 deficient CD4+ T cells[1] | | Dosage: | Diet; 0.03, 0.1, 0.3 or 1% | | Administration: | For 15 days | | Result: | Had a histological improvement in epithelial cell hyperplasia, reduced inflammatory cell infiltration and a decrease in mucus production.
Prevented an increase in the colon weight in a model of colitis induced by adoptive transfer of CD4+CD45RBhigh T cells.
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| [References]
[1] Toshihiko Sugiura, et al. Oral treatment with a novel small molecule alpha 4 integrin antagonist, AJM300, prevents the development of experimental colitis in mice. J Crohns Colitis. 2013 Dec;7(11):e533-42. DOI:10.1016/j.crohns.2013.03.014 |
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