129784-64-1Relevant academic research and scientific papers
MITHRAMYCIN DERIVATIVES HAVING INCREASED SELECTIVITY AND ANTI-CANCER ACTIVITY
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Paragraph 0090; 0120, (2019/04/05)
Mithramycin side chain carboxylic acid (MTM-SA) derivative are provided, which include a substituted amino acid derivative, a substituted amino acid dipeptide derivative, or an unsubstituted dipeptide derivative. The MTM-SA derivatives are useful for treatment of cancer or neuro-diseases associated with an aberrant erythroblast transformation-specific transcription factor. Unique MTM-SA derivatives have increased selectively toward ETS transcription factor.
Development of Mithramycin Analogues with Increased Selectivity toward ETS Transcription Factor Expressing Cancers
Mitra, Prithiba,Eckenrode, Joseph M.,Mandal, Abhisek,Jha, Amit K.,Salem, Shaimaa M.,Leggas, Markos,Rohr, Jürgen
, p. 8001 - 8016 (2018/09/06)
Mithramycin A (1) was identified as the top potential inhibitor of the aberrant ETS transcription factor EWS-FLI1, which causes Ewing sarcoma. Unfortunately, 1 has a narrow therapeutic window, compelling us to seek less toxic and more selective analogues. Here, we used MTMSA (2) to generate analogues via peptide coupling and fragment-based drug development strategies. Cytotoxicity assays in ETS and non-ETS dependent cell lines identified two dipeptide analogues, 60 and 61, with 19.1- and 15.6-fold selectivity, respectively, compared to 1.5-fold for 1. Importantly, the cytotoxicity of 60 and 61 is 100 nM in ETS cells. Molecular assays demonstrated the inhibitory capacity of these analogues against EWS-FLI1 mediated transcription in Ewing sarcoma. Structural analysis shows that positioning the tryptophan residue in a distal position improves selectivity, presumably via interaction with the ETS transcription factor. Thus, these analogues may present new ways to target transcription factors for clinical use.
New small molecule inhibitors of hepatitis C virus
Wei, Wanguo,Cai, Cuifang,Kota, Smitha,Takahashi, Virginia,Ni, Feng,Strosberg, A. Donny,Snyder, John K.
scheme or table, p. 6926 - 6930 (2010/06/16)
New small molecule inhibitors of HCV were discovered by screening a small library of indoline alkaloid-type compounds. An automated assay format was employed which allowed identification of dimerization inhibitors of core, the capsid protein of the virus. These compounds were subsequently shown to block production of infectious virus in hepatoma cells.
Intramolecular inverse electron demand Diels-Alder reactions of tryptamine with tethered heteroaromatic azadienes
Benson, Scott C.,Lee, Lily,Yang, Lydie,Snyder, John K.
, p. 1165 - 1180 (2007/10/03)
1,2,4,5-Tetrazines and 1,2,4-triazines tethered to tryptamine via the ethylamine side chain undergo intramolecular inverse electron demand cycloadditions to produce adducts with the [ABazaCE]-ring skeleton of the Aspidosperma alkaloids. (C) 2000 Elsevier Science Ltd.
α-amino-indole-3-acetic acids useful as anti-diabetic, anti-obesity and anti-atherosclerotic agents
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, (2008/06/13)
Provided are novel α-aminoindole-3-acetic acid derivatives having the formula STR1 wherein R through R9 are as defined in the specification, and pharmacologically acceptable salts of compounds wherein R9 is not OM, which are useful as anti-diabetic, anti-obesity and anti-atherosclerotic agents.
