78767-55-2Relevant articles and documents
Spatially Resolved Covalent Functionalization Patterns on Graphene
Valenta, Leo?,Kova?í?ek, Petr,Vale?, Václav,Bastl, Zdeněk,Drogowska, Karolina A.,Verhagen, Timotheus A.,Cibulka, Radek,Kalbá?, Martin
, p. 1324 - 1328 (2019)
Spatially resolved functionalization of 2D materials is highly demanded but very challenging to achieve. The chemical patterning is typically tackled by preventing contact between the reagent and material, which brings various accompanying challenges. Photochemical transformation on the other hand inherently provides remote high spatiotemporal resolution using the cleanest reagent—a photon. Herein, we combine two competing reactions on a graphene substrate to create functionalization patterns on a micrometer scale via the Mitsunobu reaction. The mild reaction conditions allow introduction of covalently dynamic linkages, which can serve as reversible labels for surface- or graphene-enhanced Raman spectroscopy characterization of the patterns prepared. The proposed methodology thus provides a pathway for local introduction of arbitrary functional groups on graphene.
Combined Cardioprotective and Adipocyte Browning Effects Promoted by the Eutomer of Dual sEH/PPARγModulator
Hartmann, Markus,Bibli, Sofia-Iris,Tews, Daniel,Ni, Xiaomin,Kircher, Theresa,Kramer, Jan S.,Kilu, Whitney,Heering, Jan,Hernandez-Olmos, Victor,Weizel, Lilia,Scriba, Gerhard K. E.,Krait, Sulaiman,Knapp, Stefan,Chaikuad, Apirat,Merk, Daniel,Fleming, Ingrid,Fischer-Posovszky, Pamela,Proschak, Ewgenij
, p. 2815 - 2828 (2021/03/09)
The metabolic syndrome (MetS) is a constellation of cardiovascular and metabolic symptoms involving insulin resistance, steatohepatitis, obesity, hypertension, and heart disease, and patients suffering from MetS often require polypharmaceutical treatment.
PTG-0861: A novel HDAC6-selective inhibitor as a therapeutic strategy in acute myeloid leukaemia
Bukhari, Shazreh,Cabral, Aaron D.,Gawel, Justyna M.,Gunning, Patrick T.,Israelian, Johan,Manaswiyoungkul, Pimyupa,Nawar, Nabanita,Olaoye, Olasunkanmi O.,Radu, Tudor B.,Raouf, Yasir S.,Sedighi, Abootaleb,Shouksmith, Andrew E.,Sina, Diana,Toutah, Krimo,de Araujo, Elvin D.
, (2020/07/03)
Dysregulated Histone Deacetylase (HDAC) activity across multiple human pathologies have highlighted this family of epigenetic enzymes as critical druggable targets, amenable to small molecule intervention. While efficacious, current approaches using non-selective HDAC inhibitors (HDACi) have been shown to cause a range of undesirable clinical toxicities. To circumvent this, recent efforts have focused on the design of highly selective HDACi as a novel therapeutic strategy. Beyond roles in regulating transcription, the unique HDAC6 (with two catalytic domains) regulates the deacetylation of α-tubulin; promoting growth factor-controlled cell motility, cell division, and metastatic hallmarks. Recent studies have linked aberrant HDAC6 function in various hematological cancers including acute myeloid leukaemia and multiple myeloma. Herein, we report the discovery, in vitro characterization, and biological evaluation of PTG-0861 (JG-265), a novel HDAC6-selective inhibitor with strong isozyme-selectivity (～36× ) and low nanomolar potency (IC50 = 5.92 nM) against HDAC6. This selectivity profile was rationalized via in silico docking studies and also observed in cellulo through cellular target engagement. Moreover, PTG-0861 achieved relevant potency against several blood cancer cell lines (e.g. MV4-11, MM1S), whilst showing limited cytotoxicity against non-malignant cells (e.g. NHF, HUVEC) and CD-1 mice. In examining compound stability and cellular permeability, PTG-0861 revealed a promising in vitro pharmacokinetic (PK) profile. Altogether, in this study we identified a novel and potent HDAC6-selective inhibitor (～4× more selective than current clinical standards – citarinostat, ricolinostat), which achieves cellular target engagement, efficacy in hematological cancer cells with a promising safety profile and in vitro PK.
