108787-56-0

Upstream product

• 16856-21-6 (S)-methyl 2-((S)-2-(((benzyloxy)carbonyl)amino)-3-phenylpropanamido)-3-(1H-indol-3-yl)propanoate 
• 83522-39-8 N^α-(tert-butoxycarbonyl)-L-phenylalanyl-L-tryptophan methyl ester 
• 13734-34-4 N-tert-butoxycarbonyl-L-phenylalanine 
• 1161-13-3 N-Cbz-L-Phe 
• 7524-52-9 (S)-tryptophan methyl ester hydrochloride 
• 4299-70-1 L-tryptophan methyl ester 
• 41518-17-6 Z-Phe-O-COO-isoBu 

Downstream Products

• 109481-43-8 Z-Asn-Phe-Phe-Trp-OMe 
• 211426-90-3 Boc-Val-Pro-Phe-Trp-OMe 
• 82597-82-8 cyclo(L-tryptophyl-L-phenylalanyl) 
• 109481-44-9 Z-Asn-Phe-Phe-Trp-N₂H₃ 
• 255378-73-5 Boc-Arg(NO₂)-Pro-Pro-Val-Pro-Phe-Trp-OMe 
• 211426-92-5 Boc-Pro-Pro-Val-Pro-Phe-Trp-OMe 

Relevant academic research and scientific papers

Synthesis and Biological Evaluations of a Series of Thaxtomin Analogues

Thaxtomins are a unique family of phytotoxins with unique 4-nitroindole and diketopiperazine fragments possessing potential herbicidal activities. This work presents the total synthesis of natural product thaxtomin C and its analogues. The extensive struc

Mithramycin 2′-Oximes with Improved Selectivity, Pharmacokinetics, and Ewing Sarcoma Antitumor Efficacy

Mithramycin A (MTM) inhibits the oncogenic transcription factor EWS-FLI1 in Ewing sarcoma, but poor pharmacokinetics (PK) and toxicity limit its clinical use. To address this limitation, we report an efficient MTM 2′-oxime (MTMox) conjugation strategy for rapid MTM diversification. Comparative cytotoxicity assays of 41 MTMox analogues using E-twenty-six (ETS) fusion-dependent and ETS fusion-independent cancer cell lines revealed improved ETS fusion-independent/dependent selectivity indices for select 2′-conjugated analogues as compared to MTM. Luciferase-based reporter assays demonstrated target engagement at low nM concentrations, and molecular assays revealed that analogues inhibit the transcriptional activity of EWS-FLI1. These in vitro screens identified MTMox32E (a Phe-Trp dipeptide-based 2′-conjugate) for in vivo testing. Relative to MTM, MTMox32E displayed an 11-fold increase in plasma exposure and improved efficacy in an Ewing sarcoma xenograft. Importantly, these studies are the first to point to simple C3 aliphatic side-chain modification of MTM as an effective strategy to improve PK.

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.

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.

(Nitro) hymenamide A, unusual biologically active cyclic peptide

A new biological active cyclic peptide (Nitro) Hymenamide A has been synthesized and the structure was established on the basis of analytical, IR, NMR and mass spectral data. The new compound was subjected to both antimicrobial and pharmacological studies.

Synthetic and biological studies on 5-(p-chlorophenyl)furan-2-carboxyl peptides and 4-[2′-(5′-formyl)furyl]benzoyl peptides

Substituted anilines are coupled with furoic acid and furfural at the position-5 to get 5-(p-chlorophenyl)furan-2-carboxylic acid and 4-[2′-(5′-formyl) furyl]benzoic acid which on further coupling with amino acid esters, di-, tetra- and hexapeptides yield