Loading…

Anti-arthritic effects of the novel dipeptidyl peptidase IV inhibitors TMC-2A and TSL-225

We evaluated the immunopharmacological effects of two novel dipeptidyl peptidase IV (DP IV) inhibitors, TMC-2A [(2S,2S′,2S″)-2-[2′-[2″-amino-3″-(-indol-3‴-yl)-1″-oxopropyl]-1′,2′,3′,4′-tetrahydro-6′,8′-dihydroxy-7′-methoxyisoquinol-3-yl-carbonylamino]-4-hydroxymethyl-5-hydroxypentanoic acid] and TSL...

Full description

Saved in:
Bibliographic Details
Published in:Immunopharmacology 1998-07, Vol.40 (1), p.21-26
Main Authors: Tanaka, Sumiko, Murakami, Takanori, Nonaka, Nobuaki, Ohnuki, Tetsuo, Yamada, Masaki, Sugita, Takahisa
Format: Article
Language:English
Subjects:
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:We evaluated the immunopharmacological effects of two novel dipeptidyl peptidase IV (DP IV) inhibitors, TMC-2A [(2S,2S′,2S″)-2-[2′-[2″-amino-3″-(-indol-3‴-yl)-1″-oxopropyl]-1′,2′,3′,4′-tetrahydro-6′,8′-dihydroxy-7′-methoxyisoquinol-3-yl-carbonylamino]-4-hydroxymethyl-5-hydroxypentanoic acid] and TSL-225 (tryptophyl-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid). TMC-2A, produced by Aspergillus sp. A374, inhibited rat kidney DP IV uncompetitively, with a Ki value of 5.3 μM. In vivo, TMC-2A suppressed alkyldiamine (N,N-dioctadecyl-N′,N-bis(2-hydroxyethyl)propanediamine)-induced arthritis. We developed a chemically modified inhibitor, TSL-225, with potency similar to that of TMC-2A. TSL-225 inhibited DP IV uncompetitively, with a Ki value of 3.6 μM. TSL-225 was also effective against adjuvant-induced arthritis. These results suggest that TMC-2A and its derivatives may have therapeutic potential for the treatment of inflammatory diseases such as rheumatoid arthritis.
ISSN:0162-3109
DOI:10.1016/S0162-3109(98)00014-9