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• 15725-29-8 2-(2,4-Dichlor-benzyliden)-acetessigsaeure-aethylester 
• 874-42-0 2,4-dichlorobenzaldeyhde 
• 103862-84-6 3-(2,4-dichlorophenyl)pentanedioic acid 

Relevant academic research and scientific papers

Use of Crystallography and Molecular Modeling for the Inhibition of the Botulinum Neurotoxin A Protease

Botulinum neurotoxins (BoNTs) are extremely toxic and have been deemed a Tier 1 potential bioterrorism agent. The most potent and persistent of the BoNTs is the "A"serotype, with strategies to counter its etiology focused on designing small-molecule inhibitors of its light chain (LC), a zinc-dependent metalloprotease. The successful structure-based drug design of inhibitors has been confounded as the LC is highly flexible with significant morphological changes occurring upon inhibitor binding. To achieve greater success, previous and new cocrystal structures were evaluated from the standpoint of inhibitor enantioselectivity and their effect on active-site morphology. Based upon these structural insights, we designed inhibitors that were predicted to take advantage of π-πstacking interactions present in a cryptic hydrophobic subpocket. Structure-activity relationships were defined, and X-ray crystal structures and docking models were examined to rationalize the observed potency differences between inhibitors.

Catch and Anchor Approach to Combat Both Toxicity and Longevity of Botulinum Toxin A

Botulinum neurotoxins have remarkable persistence (～weeks to months in cells), outlasting the small-molecule inhibitors designed to target them. To address this disconnect, inhibitors bearing two pharmacophores - a zinc binding group and a Cys-reactive wa

ALLOSTERIC PROTEIN KINASE MODULATORS

The invention provides specific small molecule compounds that allosterically regulate the activity or modulate protein-protein interactions of AGC protein kinases and the Aurora family of protein kinases, methods for their production, pharmaceutical compositions comprising same, and their use for preparing medicaments for the treatment and prevention of diseases related to abnormal activities of AGC protein kinases or of protein kinases of the Aurora family.

4-benzimidazolyl-3-phenylbutanoic acids as novel pif-pocket-targeting allosteric inhibitors of protein kinase PKCΧ

Protein kinase inhibitors with an allosteric mode of action are expected to reach, in many cases, higher selectivity for the target enzyme than ATP-competitive compounds. Therefore, basic research is aiming at identifying and establishing novel sites on the catalytic domain of protein kinases which might be targeted by allosteric inhibitors. We previously published the first structure-activity relationships (SARs) for allosteric activators of protein kinase PDK1. Here, we present the design, synthesis, and SAR data on a series of novel compounds, 4-benzimidazolyl-3-phenylbutanoic acids, that inhibit the atypical protein kinace C (PKC) Χ via binding to the PIF-pocket. Key positions were identified in the compounds that can be modified to increase potency and selectivity. Some congeners showed a high selectivity toward PKCΧ, lacking inhibition of the most closely related isoform, PKC1, and of further AGC kinases. Furthermore, evidence is provided that these compounds are also active toward cellular PKCΧ without loss of potency compared to the cell-free assay.

ALLOSTERIC PROTEIN KINASE MODULATORS

The invention provides specific small molecule compounds that allosterically regulate the activity or modulate protein-protein interactions of AGC protein kinases and the Aurora family of protein kinases, methods for their production, pharmaceutical compositions comprising same, and their use for preparing medicaments for the treatment and prevention of diseases related to abnormal activities of AGC protein kinases or of protein kinases of the Aurora family.