164470-64-8Relevant articles and documents
Simple methods for tracking stem cells with 64Cu-labeled DOTA-hexadecyl-benzoate
Kim, Min Hwan,Woo, Sang-Keun,Kim, Kwang Il,Lee, Tae Sup,Kim, Chan Wha,Kang, Joo Hyun,Kim, Byung Il,Lim, Sang Moo,Lee, Kyo Chul,Lee, Yong Jin
, p. 528 - 530 (2015)
The purpose of this study was to evaluate 64Cu-labeled hexadecyl-1,4,7,10-tetraazacyclododecane-tetraacetic acid-benzoate (64Cu-DOTA-HB) (1) as positron emission tomography (PET) radiotracer for stem cell imaging. Hexadecyl-DOTA-benzoate (DOTA-HB) (2) was efficiently labeled with 64Cu (>99%), and cell labeling efficiency with adipose-derived stem cells (ADSCs) was over 50%. Labeling with 1 did not compromise cell viability. In the PET imaging, intramuscularly transplanted 1-labeled ADSCs were monitored for 18 h in normal rat heart. These results indicate that 1 can be utilized as a promising radiotracer for monitoring of transplanted stem cells.
Development of anti-inflammatory peptidomimetics based on the structure of human alpha1-antitrypsin
Lior, Yotam,Shtriker, Efrat,Kahremany, Shirin,Lewis, Eli C.,Gruzman, Arie
supporting information, (2021/11/16)
Human α1-antitrypsin (hAAT) has two distinguishing functions: anti-protease activity and regulation of the immune system. In the present study we hypothesized that those two protein functions are mediated by different structural domains on the hAAT surface. Indeed, such biologically active immunoregulatory sites (not associated with canonical anti-protease activity) on the surface of hAAT were identified by in silico methods. Several peptides were derived from those immunoregulatory sites. Four peptides exhibited impressive biological effects in pharmacological concentration ranges. Peptidomimetic (14) was developed, based on the structure of the most druggable and active peptide. The compound exhibited a potent anti-inflammatory activity in vitro and in vivo. Such a compound could be used as a basis for developing novel anti-inflammatory drug candidates and as a research tool for better understanding hAAT functions.
Beyond Basicity: Discovery of Nonbasic DENV-2 Protease Inhibitors with Potent Activity in Cell Culture
Kühl, Nikos,Leuthold, Mila M.,Behnam, Mira A. M.,Klein, Christian D.
supporting information, p. 4567 - 4587 (2021/05/06)
The viral serine protease NS2B-NS3 is one of the promising targets for drug discovery against dengue virus and other flaviviruses. The molecular recognition preferences of the protease favor basic, positively charged moieties as substrates and inhibitors, which leads to pharmacokinetic liabilities and off-target interactions with host proteases such as thrombin. We here present the results of efforts that were aimed specifically at the discovery and development of noncharged, small-molecular inhibitors of the flaviviral proteases. A key factor in the discovery of these compounds was a cellular reporter gene assay for the dengue protease, the DENV2proHeLa system. Extensive structure-activity relationship explorations resulted in novel benzamide derivatives with submicromolar activities in viral replication assays (EC50 0.24 μM), selectivity against off-target proteases, and negligible cytotoxicity. This structural class has increased drug-likeness compared to most of the previously published active-site-directed flaviviral protease inhibitors and includes promising candidates for further preclinical development.
The spectrum between substrates and inhibitors: Pinpointing the binding mode of dengue protease ligands with modulated basicity and hydrophobicity
Gottscheber, Nicole,Hacker, Christina N.,Klein, Christian D.,Dra?i?, Tonko,Kühl, Nikos
supporting information, (2021/10/02)
Peptides can be inhibitors and substrates of proteases. The present study describes the inhibitor- vs. substrate-like properties of peptidic ligands of dengue protease which were designed to provide insight into their binding modes. Of particular interest was the localization of the cleavable peptide bond and the placement of hydrophobic elements in the binding site. The findings provide clues for the design of covalent inhibitors in which electrophilic functional groups bind to the catalytic serine, and in addition for the development of inhibitors that are less basic than the natural substrate and therefore have an improved pharmacokinetic profile. We observed a tendency of basic elements to favor a substrate-like binding mode, whereas hydrophobic elements decrease or eliminate enzymatic cleavage. This indicates a necessity to include basic elements which closely mimic the natural substrates into covalent inhibitors, posing a challenge from the chemical and pharmacokinetic perspective. However, hydrophobic elements may offer opportunities to develop non-covalent inhibitors with a favorable ADME profile and potentially improved target-binding kinetics.
Exploring Structural Determinants of Inhibitor Affinity and Selectivity in Complexes with Histone Deacetylase 6
Osko, Jeremy D.,Porter, Nicholas J.,Narayana Reddy, Poli Adi,Xiao, You-Cai,Rokka, Johanna,Jung, Manfred,Hooker, Jacob M.,Salvino, Joseph M.,Christianson, David W.
, p. 295 - 308 (2020/02/20)
Inhibition of histone deacetylase 6 (HDAC6) has emerged as a promising therapeutic strategy for the treatment of cancer, chemotherapy-induced peripheral neuropathy, and neurodegenerative disease. The recent X-ray crystal structure determination of HDAC6 enables an understanding of structural features directing affinity and selectivity in the active site. Here, we present the X-ray crystal structures of five HDAC6-inhibitor complexes that illuminate key molecular features of the inhibitor linker and capping groups that facilitate and differentiate binding to HDAC6. In particular, aromatic and heteroaromatic linkers nestle within an aromatic cleft defined by F583 and F643, and different aromatic linkers direct the capping group toward shallow pockets defined by the L1 loop, the L2 loop, or somewhere in between these pockets. These results expand our understanding of factors contributing to the selective inhibition of HDAC6, particularly regarding interactions that can be targeted in the region of the L2 pocket.
Dual PPAR-δ PPAR-γ agonists
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Page/Page column 89, (2016/09/26)
The present disclosure provides novel compounds with activity as PPARβ/δ and PPARγ dual agonists. The disclosure also provides methods of treating diabetes mellitus and methods of treating Alzheimer's disease utilizing the novel compounds, as well as phar
ANTIMICROBIAL COMPOUNDS
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Page/Page column 39, (2015/05/19)
The invention provides compounds for use in treating microbial infection in an animal. Example compounds include Pyridin-3-ylmethyl (4-((2-aminophenyl)- carbamoyl)benzyl)carbamate ("Entinostat"). The compounds can act via induction of the innate antimicrobial peptide defense system, and stimulation of autophagy.
Synthesis, biological evaluation, and docking studies of PAR2-AP-derived pseudopeptides as inhibitors of kallikrein 5 and 6
Severino, Beatrice,Fiorino, Ferdinando,Corvino, Angela,Caliendo, Giuseppe,Santagada, Vincenzo,Assis, Diego Magno,Oliveira, Juliana R.,Juliano, Luiz,Manganelli, Serena,Benfenati, Emilio,Frecentese, Francesco,Perissutti, Elisa,Juliano, Maria Aparecida
, p. 45 - 52 (2015/02/19)
A series of protease activated receptor 2 activating peptide (PAR2-AP) derivatives (1-15) were designed and synthesized. The obtained compounds were tested on a panel of human kallikreins (hKLK1, hKLK2, hKLK5, hKLK6, and hKLK7) and were found completely i
Design, development and evaluation of novel dual PPARδ/PPARγ agonists
Gathiaka, Symon,Nanayakkara, Gayani,Boncher, Tracey,Acevedo, Orlando,Wyble, Johnathon,Patel, Sagar,Patel, Akash,Shane, Mary Elizabeth,Bonkowski, Blake,Wieczorek, Jason,Rong, Yinghui,Huggins, Kevin,Smith, Forest,Amin, Rajesh H.
, p. 873 - 879 (2013/02/23)
Type 2 diabetes is at epidemic proportions and thus development of novel pharmaceutical therapies for improving insulin sensitivity has become of paramount importance. The objectives of the current study were to develop novel dual PPARγ/δ agonists without
Direct Fmoc-chemistry-based solid-phase synthesis of peptidyl thioesters
Sharma, Indrajeet,Crich, David
scheme or table, p. 6518 - 6524 (2011/10/02)
Attachment of a growing peptide chain to a glycylaminomethyl resin via a thioglycinamide bond is compatible with Fmoc-chemistry solid-phase peptide synthesis. Subsequent S-alkylation of the thioamide gives a thioimide that, on treatment with aqueous trifl
