carotegrast   Click here for help

GtoPdb Ligand ID: 10511

Synonyms: HCA2969
Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: Carotegrast (HCA2969) is the active metabolite of carotegrast methyl [1,4]. It acts as an antagonist of α4 integrin-mediated transmigration of leukocytes to sites of inflammation. The chemical structure of carotegrast is claimed as example 108 in EA Pharma patent US20110065918A1 which claims phenylalanine derivatives as α4 integrin antagonists for use as clinical therapeutics [2].
Click here for help
2D Structure
Click here for help
Click here for structure editor
Physico-chemical Properties
Click here for help
Hydrogen bond acceptors 5
Hydrogen bond donors 2
Rotatable bonds 8
Topological polar surface area 113.12
Molecular weight 554.11
XLogP 6.12
No. Lipinski's rules broken 1
Click here for help
Canonical SMILES CN(c1ccc2c(c1)c(=O)n(c(=O)n2C)c1ccc(cc1)CC(C(=O)O)NC(=O)c1c(Cl)cccc1Cl)C
Isomeric SMILES CN(c1ccc2c(c1)c(=O)n(c(=O)n2C)c1ccc(cc1)C[C@@H](C(=O)O)NC(=O)c1c(Cl)cccc1Cl)C
InChI 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
Immunopharmacology Comments
Carotegrast produces the same functional outcome as the anti-α4 integrin antibody natalizumab, but with the benefits associated with small-molecule drugs [3,5-6]. 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.