carotegrast methyl   Click here for help

GtoPdb Ligand ID: 10510

Synonyms: AJM-300 | AJM300
Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: Carotegrast methyl (AJM300) is an orally administered esterified prodrug α4 integrin inhibitor/antagonist that was developed by EA Pharma for anti-inflammatory potential [1].
2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 5
Hydrogen bond donors 1
Rotatable bonds 9
Topological polar surface area 102.12
Molecular weight 568.13
XLogP 6.44
No. Lipinski's rules broken 1
SMILES / InChI / InChIKey
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Canonical SMILES COC(=O)C(NC(=O)c1c(Cl)cccc1Cl)Cc1ccc(cc1)n1c(=O)c2cc(ccc2n(c1=O)C)N(C)C
Isomeric SMILES COC(=O)[C@@H](NC(=O)c1c(Cl)cccc1Cl)Cc1ccc(cc1)n1c(=O)c2cc(ccc2n(c1=O)C)N(C)C
InChI 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
InChI Key MMHHPKCJJIFLBQ-QFIPXVFZSA-N
Immunopharmacology Comments
Carotegrast methyl (AJM300) is a small-molecule anti-integrin prodrug. Its active metabolite, carotegrast, produces the same functional outcome as the anti-α4 antibody natalizumab, but with the benefits associated with small-molecule drugs [2-4]. Specifically, carotegrast blocks interactions between α4β1 and α4β7 integrins with their counter-receptors (VCAM-1 and MAdCAM-1 respectively) and fibronectin, and this mechanism limits transmigration of leukocytes into sites of inflammation.