TMC-95B
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| Category | Enzyme inhibitors |
| Catalog number | BBF-02535 |
| CAS | |
| Molecular Weight | 678.7 |
| Molecular Formula | C33H38N6O10 |
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Description
TMC-95B is a proteasome inhibitor produced by Apiospora montagnei Sacc. TC 1093. It inhibited the chymotrypsin-like (ChT-L), trypsin-like (T-L), and peptidylglutamyl-peptide hydrolyzing (PGPH) activities of 20S proteasome to the same extent as TMC-95A.
Specification
| Synonyms | TMC-95 B |
| IUPAC Name | (10S,11R,12S,15S,18S)-15-(2-amino-2-oxoethyl)-10,11,23-trihydroxy-18-[[(3R)-3-methyl-2-oxopentanoyl]amino]-9,14,17-trioxo-N-[(Z)-prop-1-enyl]-8,13,16-triazatetracyclo[18.3.1.02,7.06,10]tetracosa-1(23),2(7),3,5,20(24),21-hexaene-12-carboxamide |
| Canonical SMILES | CCC(C)C(=O)C(=O)NC1CC2=CC(=C(C=C2)O)C3=C4C(=CC=C3)C(C(C(NC(=O)C(NC1=O)CC(=O)N)C(=O)NC=CC)O)(C(=O)N4)O |
| InChI | InChI=1S/C33H38N6O10/c1-4-11-35-30(46)25-27(43)33(49)19-8-6-7-17(24(19)39-32(33)48)18-12-16(9-10-22(18)40)13-20(37-31(47)26(42)15(3)5-2)28(44)36-21(14-23(34)41)29(45)38-25/h4,6-12,15,20-21,25,27,40,43,49H,5,13-14H2,1-3H3,(H2,34,41)(H,35,46)(H,36,44)(H,37,47)(H,38,45)(H,39,48)/b11-4-/t15-,20+,21+,25+,27-,33+/m1/s1 |
| InChI Key | ZIAXNZCTODBCKW-NKGUOCGVSA-N |
Reference Reading
1. Simplified synthetic TMC-95A/B analogues retain the potency of proteasome inhibitory activity
Zhi-Qiang Yang, Benjamin H B Kwok, Songnian Lin, Michael A Koldobskiy, Craig M Crews, Samuel J Danishefsky Chembiochem. 2003 Jun 6;4(6):508-13. doi: 10.1002/cbic.200300560.
The proteasome regulates diverse intracellular processes, including cell-cycle progression, antigen presentation, and inflammatory response. Selective inhibitors of the proteasome have great therapeutic potential for the treatment of cancer and inflammatory disorders. Natural cyclic peptides TMC-95A and B represent a new class of noncovalent, selective proteasome inhibitors. To explore the structure-activity relationship of this class of proteasome inhibitors, a series of TMC-95A/B analogues were prepared and analyzed. We found that the unique enamide functionality at the C8 position of TMC-95s can be replaced with a simple allylamide. The asymmetric center at C36 that distinguishes TMC-95A from TMC-95B but which necessitates a complicated separation of the two compounds can be eliminated. Therefore, these findings could lead to the development of more accessible simple analogues as potential therapeutic agents.
2. Total synthesis of TMC-95A and -B via a new reaction leading to Z-enamides. Some preliminary findings as to SAR
Songnian Lin, Zhi-Qiang Yang, Benjamin H B Kwok, Michael Koldobskiy, Craig M Crews, Samuel J Danishefsky J Am Chem Soc. 2004 May 26;126(20):6347-55. doi: 10.1021/ja049821k.
A full account of the total syntheses of proteasome inhibitors TMC-95A and -B is provided. A key feature of the syntheses involved installation of a cis-propenylamide moiety by a thermal rearrangement of an alpha-silylallyl amide. The scope and mechanism of the enamide-forming reaction are discussed. Also provided are some preliminary results from SAR studies. It was found that simplified analogues can retain the full potency of proteasome inhibition.
3. A concise, total synthesis of the TMC-95A/B proteasome inhibitors
Brian K Albrecht, Robert M Williams Proc Natl Acad Sci U S A. 2004 Aug 17;101(33):11949-54. doi: 10.1073/pnas.0308432101. Epub 2004 May 26.
A concise, total synthesis of the proteasome inhibitors TMC-95A/B has been accomplished. The synthesis features the use of an L-serine-derived E-selective modified Julia olefination reaction to ultimately control the stereochemical outcome of the highly oxidized tryptophan fragment. Additionally, the limited use of protecting groups at a late stage of the total synthesis allowed for its completion in an efficient manner.
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Bio Calculators
* Our calculator is based on the following equation:
Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
It is commonly abbreviated as: C1V1 = C2V2
* Total Molecular Weight:
g/mol
Tip: Chemical formula is case sensitive. C22H30N4O √ c22h30n40 ╳
