213015-69-1

Upstream product

• 349-88-2 4-Fluorobenzenesulfonyl chloride 
• 27532-96-3 glycine tert-butyl ester hydrochloride 
• 13029-71-5 2-(4-fluorophenylsulfonamido)acetic acid 
• 36805-97-7 N,N-dimethylformamide di-tert-butyl acetal 

Downstream Products

• 245364-73-2 [(4-chloro-benzyl)-(4-fluoro-benzenesulfonyl)-amino]-acetic acid tert-butyl ester 
• 2361659-61-0 C₃₃H₂₉F₆N₃O₅S 
• 245365-02-0 N-benzyloxy-2-[(4-chloro-benzyl)-(4-fluoro-benzenesulfonyl)-amino]-acetamide 
• 245365-05-3 N-benzyloxy-2-[(4-fluoro-benzenesulfonyl)-(4-methyl-benzyl)-amino]-acetamide 
• 245364-99-2 2-[benzyl-(4-fluoro-benzenesulfonyl)-amino]-N-benzyloxy-acetamide 
• 276695-39-7 N-benzyl-N-[(4-fluorophenyl)sulfonyl]glycine 
• 287407-11-8 2-[(4-but-2-ynylthiophenylsulfonyl)methylamino]acetic acid tert-butyl ester 

Relevant academic research and scientific papers

Identification and Characterization of AES-135, a Hydroxamic Acid-Based HDAC Inhibitor That Prolongs Survival in an Orthotopic Mouse Model of Pancreatic Cancer

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive, incurable cancer with a 20% 1 year survival rate. While standard-of-care therapy can prolong life in a small fraction of cases, PDAC is inherently resistant to current treatments, and novel therapies are urgently required. Histone deacetylase (HDAC) inhibitors are effective in killing pancreatic cancer cells in in vitro PDAC studies, and although there are a few clinical studies investigating combination therapy including HDAC inhibitors, no HDAC drug or combination therapy with an HDAC drug has been approved for the treatment of PDAC. We developed an inhibitor of HDACs, AES-135, that exhibits nanomolar inhibitory activity against HDAC3, HDAC6, and HDAC11 in biochemical assays. In a three-dimensional coculture model, AES-135 kills low-passage patient-derived tumor spheroids selectively over surrounding cancer-associated fibroblasts and has excellent pharmacokinetic properties in vivo. In an orthotopic murine model of pancreatic cancer, AES-135 prolongs survival significantly, therefore representing a candidate for further preclinical testing.

Class I/IIb-Selective HDAC Inhibitor Exhibits Oral Bioavailability and Therapeutic Efficacy in Acute Myeloid Leukemia

The HDAC inhibitor 4-tert-butyl-N-(4-(hydroxycarbamoyl)phenyl)benzamide (AES-350, 51) was identified as a promising preclinical candidate for the treatment of acute myeloid leukemia (AML), an aggressive malignancy with a meagre 24% 5-year survival rate. Through screening of low-molecular-weight analogues derived from the previously discovered novel HDAC inhibitor, AES-135, compound 51 demonstrated greater HDAC isoform selectivity, higher cytotoxicity in MV4-11 cells, an improved therapeutic window, and more efficient absorption through cellular and lipid membranes. Compound 51 also demonstrated improved oral bioavailability compared to SAHA in mouse models. A broad spectrum of experiments, including FACS, ELISA, and Western blotting, were performed to support our hypothesis that 51 dose-dependently triggers apoptosis in AML cells through HDAC inhibition.

Acetylenic TACE inhibitors. Part 1. SAR of the acyclic sulfonamide hydroxamates

The SAR of a series of potent sulfonamide hydroxamate TACE inhibitors, all bearing a butynyloxy P1′ group, was explored. In particular, compound 5j has excellent in vitro potency against isolated TACE enzyme and in cells, good selectivity over MMP-1 and MMP-9, and oral activity in an in vivo model of TNF-α production and a collagen-induced arthritis model.

Synthesis of an array of potential matrix metalloproteinase inhibitors using a sequence of polymer-supported reagents

Polymer-supported reagents and sequestering agents may be used to generate an array of variously substituted hydroxamic acid derivatives as potential inhibitors of matrix metalloproteinases without any chromatographic purification step.