871498-18-9

Usage

Chemical compound

2-amino-3-(6-fluoro-1H-indol-3-yl)-propionic acid methyl ester

Chemical classification

Methyl ester derivative

Derivative of

2-amino-3-(6-fluoro-1H-indol-3-yl)-propionic acid
Synthetic derivative of the neurotransmitter glutamate
Acts as an agonist at the glutamate receptors

Specific receptors targeted

Group I metabotropic glutamate receptors
Studied for potential use in the treatment of neurological disorders

Neurological disorders studied for

Alzheimer's disease, Parkinson's disease, schizophrenia
Investigated for potential role in modulating synaptic plasticity
Research focus on development of new therapeutic strategies for cognitive impairment and memory deficits
More research needed for full understanding of pharmacological properties and clinical applications

Upstream product

• 67-56-1 methanol 
• 19310-00-0 6-fluoro-L-tryptophan 

Relevant academic research and scientific papers

MITHRAMYCIN DERIVATIVES HAVING INCREASED SELECTIVITY AND ANTI-CANCER ACTIVITY

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

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.

N-benzoyl amino acids as LFA-1/ICAM inhibitors 1: Amino acid structure-activity relationship

The association of ICAM-1 with LFA-1 plays a critical role in several autoimmune diseases. N-2-Bromobenzoyl L-tryptophan, compound 1, was identified as an inhibitor to the formation of the LFA-1/ICAM complex. The SAR of the amino acid indicates that the carboxylic acid is required for inhibition and that L-histidine is the most favored amino acid.