347174-28-1Relevant articles and documents
An Aza-Cope Reactivity-Based Fluorescent Probe for Imaging Formaldehyde in Living Cells
Brewer, Thomas F.,Chang, Christopher J.
, p. 10886 - 10889 (2015)
Formaldehyde (FA) is a reactive carbonyl species (RCS) produced in living systems that has been implicated in epigenetics as well as in the pathologies of various cancers, diabetes, and heart, liver, and neurodegenerative diseases. Traditional methods for biological FA detection rely on sample destruction and/or extensive processing, resulting in a loss of spatiotemporal information. To help address this technological gap, we present the design, synthesis, and biological evaluation of a fluorescent probe for live-cell FA imaging that relies on a FA-induced aza-Cope rearrangement. Formaldehyde probe-1 (FAP-1) is capable of detecting physiologically relevant concentrations of FA in aqueous buffer and in live cells with high selectivity over potentially competing biological analytes. Moreover, FAP-1 can visualize endogenous FA produced by lysine-specific demethylase 1 in a breast cancer cell model, presaging the potential utility of this chemical approach to probe RCS biology.
Invention of MK-8262, a Cholesteryl Ester Transfer Protein (CETP) Inhibitor Backup to Anacetrapib with Best-in-Class Properties ()
Vachal, Petr,Duffy, Joseph L.,Campeau, Louis-Charles,Amin, Rupesh P.,Mitra, Kaushik,Murphy, Beth Ann,Shao, Pengcheng P.,Sinclair, Peter J.,Ye, Feng,Katipally, Revathi,Lu, Zhijian,Ondeyka, Debra,Chen, Yi-Heng,Zhao, Kake,Sun, Wanying,Tyagarajan, Sriram,Bao, Jianming,Wang, Sheng-Ping,Cote, Josee,Lipardi, Concetta,Metzger, Daniel,Leung, Dennis,Hartmann, Georgy,Wollenberg, Gordon K.,Liu, Jian,Tan, Lushi,Xu, Yingju,Chen, Qinghao,Liu, Guiquan,Blaustein, Robert O.,Johns, Douglas G.
supporting information, p. 13215 - 13258 (2021/09/02)
Cholesteryl ester transfer protein (CETP) represents one of the key regulators of the homeostasis of lipid particles, including high-density lipoprotein (HDL) and low-density lipoprotein (LDL) particles. Epidemiological evidence correlates increased HDL and decreased LDL to coronary heart disease (CHD) risk reduction. This relationship is consistent with a clinical outcomes trial of a CETP inhibitor (anacetrapib) combined with standard of care (statin), which led to a 9% additional risk reduction compared to standard of care alone. We discuss here the discovery of MK-8262, a CETP inhibitor with the potential for being the best-in-class molecule. Novel in vitro and in vivo paradigms were integrated to drug discovery to guide optimization informed by a critical understanding of key clinical adverse effect profiles. We present preclinical and clinical evidence of MK-8262 safety and efficacy by means of HDL increase and LDL reduction as biomarkers for reduced CHD risk.
HOMOALLYLAMINES AS FORMALDEHYDE-RESPONSIVE TRIGGERS
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Paragraph 00233, (2017/03/14)
Probes for formaldehyde (FA) including a homoallylamine trigger group attached to a detectable moiety are provided. Aspects of the probes include luminogenic or fluorogenic probes, such as a probe including a quencher in energy-receiving proximity to a fl
Intracellular Protein-Labeling Probes for Multicolor Single-Molecule Imaging of Immune Receptor-Adaptor Molecular Dynamics
Sato, Ryota,Kozuka, Jun,Ueda, Masahiro,Mishima, Reiko,Kumagai, Yutaro,Yoshimura, Akimasa,Minoshima, Masafumi,Mizukami, Shin,Kikuchi, Kazuya
supporting information, p. 17397 - 17404 (2017/12/15)
Single-molecule imaging (SMI) has been widely utilized to investigate biomolecular dynamics and protein-protein interactions in living cells. However, multicolor SMI of intracellular proteins is challenging because of high background signals and other lim
BICYCLOHETEROARYL-HETEROARYL-BENZOIC ACID COMPOUNDS AS RETINOIC ACID RECEPTOR BETA (RARβ) AGONISTS
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Page/Page column 105; 106, (2016/07/05)
The present invention pertains generally to the field of therapeutic compounds, and more specifically to certain bicycloheteroaryl-heteroaryl-benzoic acid compounds of the following formula (for convenience, collectively referred to herein as "BHBA compou
Silicon and germanium dyes for use in genetic identity
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, (2015/11/16)
Si- and Ge-based dyes and methods of using same.
Aarhus green: A tetrafluoro-substituted derivative of fluorescein
Holmehave, Jeppe,Pedersen, Stephan K.,Jensen, Henrik H.,Ogilby, Peter R.
, p. 52 - 64 (2015/03/31)
The synthesis and characterization of a 2′,4′,5′,7′-tetrafluorinated derivative of fluorescein, called Aarhus Green, is reported. As with related 2′,7′-difluorinated compounds, tetrafluorination of the xanthene-derived moiety makes the more fluorescent anion accessible over a larger pH range. However, in contrast to a published report, we find that fluorination in the 4′ and 5′ positions does not appreciably decrease the fluorescence quantum yield, φf. Rather, Aarhus Green has a reasonably large φf (0.79 ± 0.04). Moreover, Aarhus Green does not efficiently sensitize the production of singlet oxygen and it is photostable. Thus, tetrafluorination of the xanthene moiety in fluorescein derivatives can be a useful tool in the development of fluorescent probes.
BICYCLIC UREAS AND THIADIAZOLIDINE-1,1-DIOXIDES AS CETP INHIBITORS
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Page/Page column 40, (2015/02/25)
Compounds having the structure of Formula I, including pharmaceutically acceptable salts of the compounds, wherein X is -C(=O) or -S(O)2-, are CETP inhibitors and are useful for raising HDL-cholesterol, reducing LDL-cholesterol, and for treating or preventing atherosclerosis.
A Cu-free clickable fluorescent probe for intracellular targeting of small biomolecules
Yamagishi, Kento,Sawaki, Kazuaki,Murata, Atsushi,Takeoka, Shinji
supporting information, p. 7879 - 7882 (2015/05/05)
We synthesized a novel cyclooctyne-based clickable fluorescent probe with versatile properties such as high cell-membrane permeability and free diffusibility in the cell. Our probe "FC-DBCO" was conjugated to an azide-modified mannose via a Cu-free click
Cell Permeable, Fluorescent Dye
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Paragraph 0128-0131, (2014/12/09)
The invention pertains to a near-infrared fluorescent dye that is cell permeable and can be attached to selected proteins in living cells. The dye has the general formula or its corresponding spirolactone wherein Y is chosen from the group consisting of S