TMC-2A
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| Category | Enzyme inhibitors |
| Catalog number | BBF-02519 |
| CAS | |
| Molecular Weight | 570.6 |
| Molecular Formula | C28H34N4O9 |
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Description
TMC-2A is a dipeptidyl peptidase IV (DPIV) inhibitor isolated from the fermentation broth of Aspergillus oryzae A374. It inhibited rat kidney DPIV with IC50 value of 8.1 μmol/L.
Specification
| Synonyms | TMC-2 A |
| IUPAC Name | (2S)-2-[[(3S)-2-[(2S)-2-amino-3-(1H-indol-3-yl)propanoyl]-6,8-dihydroxy-7-methoxy-3,4-dihydro-1H-isoquinoline-3-carbonyl]amino]-5-hydroxy-4-(hydroxymethyl)pentanoic acid |
| Canonical SMILES | COC1=C(C=C2CC(N(CC2=C1O)C(=O)C(CC3=CNC4=CC=CC=C43)N)C(=O)NC(CC(CO)CO)C(=O)O)O |
| InChI | InChI=1S/C28H34N4O9/c1-41-25-23(35)9-15-8-22(26(37)31-21(28(39)40)6-14(12-33)13-34)32(11-18(15)24(25)36)27(38)19(29)7-16-10-30-20-5-3-2-4-17(16)20/h2-5,9-10,14,19,21-22,30,33-36H,6-8,11-13,29H2,1H3,(H,31,37)(H,39,40)/t19-,21-,22-/m0/s1 |
| InChI Key | ODKDMMTXTVCCLJ-BVSLBCMMSA-N |
Properties
| Appearance | White Powder |
| Melting Point | 166-169°C (dec.) |
Reference Reading
1. Anti-arthritic effects of the novel dipeptidyl peptidase IV inhibitors TMC-2A and TSL-225
S Tanaka, T Murakami, N Nonaka, T Ohnuki, M Yamada, T Sugita Immunopharmacology. 1998 Jul;40(1):21-6. doi: 10.1016/s0162-3109(98)00014-9.
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-car bonylamino]-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 microM. 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 microM. 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.
2. TMC-2A, -2B and -2C, new dipeptidyl peptidase IV inhibitors produced by Aspergillus oryzae A374. II. Isolation and structure determination
Y Asai, N Nonaka, M Nishio, K Okamura, T Date, T Sugita, T Ohnuki, S Komatsubara J Antibiot (Tokyo). 1997 Aug;50(8):653-8. doi: 10.7164/antibiotics.50.653.
New dipeptidyl peptidase IV inhibitors, TMC-2A, -2B, and -2C, were isolated from the fermentation broth of Aspergillus oryzae A374. On the basis of chemical, spectroscopic and X-ray crystallographic analyses, their structures were established to be peptide-like compounds composed of three moieties, L-tryptophan, mono- or dihydroxy-L-leucine and highly substituted isoquinoline.
3. Dipeptidyl peptidase IV on activated T cells as a target molecule for therapy of rheumatoid arthritis
Y N Williams, H Baba, S Hayashi, H Ikai, T Sugita, S Tanaka, N Miyasaka, T Kubota Clin Exp Immunol. 2003 Jan;131(1):68-74. doi: 10.1046/j.1365-2249.2003.02020.x.
The extracellular domain of the T cell co-stimulatory molecule CD26 possesses dipeptidyl peptidase IV (DP IV) enzyme activity. Activated T cells are known to increase expression of cell surface DP IV and some specific inhibitors of this enzyme have been reported to suppress T cell function. Previously we have identified a DP IV inhibitor, designated TMC-2, found in culture supernatant of Aspergillus oryzae. Administration of TMC-2 to rats with adjuvant arthritis caused marked suppression of paw swelling. To elucidate the mechanism of TMC-2 antiarthritic activity, we have studied its effects on T cell function. Here we show that TMC-2 inhibited DP IV activity of CD26 immunoprecipitated from T cell lysates, and also inhibited proliferative responses of T cells to specific antigen or anti-CD3 antibody. Suppression of IL-2 production was demonstrated at both the mRNA and protein levels. TMC-2 did not alter the PTPase activity of pure CD45, but when this molecule was co-precipitated from T cell lysates together with associated CD26, its PTPase was virtually completely abolished by TMC-2. These results suggest that modulation of CD45 PTPase activity might be responsible for functional suppression of T cells by TMC-2. Because the effects of TMC-2 on T cells were reversible and it was not toxic at the concentrations used, TMC-2 may be a candidate novel therapeutic agent for rheumatoid arthritis.
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Bio Calculators
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Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
It is commonly abbreviated as: C1V1 = C2V2
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g/mol
Tip: Chemical formula is case sensitive. C22H30N4O √ c22h30n40 ╳
