Tag: 163.99

Application of Atypical Acetyl-lysine Methyl Mimetics in the Development of Selective Inhibitors of the Bromodomain-Containing Protein 7 (BRD7)/Bromodomain-Containing Protein 9 (BRD9) Bromodomains was written by Clegg, Michael A.;Bamborough, Paul;Chung, Chun-wa;Craggs, Peter D.;Gordon, Laurie;Grandi, Paola;Leveridge, Melanie;Lindon, Matthew;Liwicki, Gemma M.;Michon, Anne-Marie;Molnar, Judit;Rioja, Inmaculada;Soden, Peter E.;Theodoulou, Natalie H.;Werner, Thilo;Tomkinson, Nicholas C. O.;Prinjha, Rab K.;Humphreys, Philip G.. And the article was included in Journal of Medicinal Chemistry in 2020.Product Details of 823-58-5 This article mentions the following:

Non-BET bromodomain-containing proteins have become attractive targets for the development of novel therapeutics targeting epigenetic pathways. To help facilitate the target validation of this class of proteins, structurally diverse small-mol. ligands and methodologies to produce selective inhibitors in a predictable fashion are in high demand. Herein, we report the development and application of atypical acetyl-lysine (KAc) Me mimetics to take advantage of the differential stability of conserved water mols. in the bromodomain binding site. Discovery of the Bu group as an atypical KAc Me mimetic allowed generation of 31 (GSK6776) as a soluble, permeable, and selective BRD7/9 inhibitor from a pyridazinone template. The Bu group was then used to enhance the bromodomain selectivity of an existing BRD9 inhibitor and to transform pan-bromodomain inhibitors into BRD7/9 selective compounds Finally, a solvent-exposed vector was defined from the pyridazinone template to enable bifunctional mol. synthesis, and affinity enrichment chemoproteomic experiments were used to confirm several of the endogenous protein partners of BRD7 and BRD9, which form part of the chromatin remodeling PBAF and BAF complexes, resp. In the experiment, the researchers used many compounds, for example, 4-Amino-3,6-dichloropyridazine (cas: 823-58-5Product Details of 823-58-5).

4-Amino-3,6-dichloropyridazine (cas: 823-58-5) belongs to pyridazine derivatives. The pyridazine structure is a popular pharmacophore which is found within a number of herbicides such as credazine, pyridafol and pyridate. The unsubstituted pyridazines are more resistant to eletrophilic substitution due to the nature of withdrawal of electron density from the ring by two heteroatoms, while the related electron deficiency of the ring makes pyridazine more easily attacked by nucleophiles.Product Details of 823-58-5

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Quantitative Characterization of Bivalent Probes for a Dual Bromodomain Protein, Transcription Initiation Factor TFIID Subunit 1 was written by Suh, Junghyun L.;Watts, Brian;Stuckey, Jacob I.;Norris-Drouin, Jacqueline L.;Cholensky, Stephanie H.;Dickson, Bradley M.;An, Yi;Mathea, Sebastian;Salah, Eidarus;Knapp, Stefan;Khan, Abid;Adams, Alexander T.;Strahl, Brian D.;Sagum, Cari A.;Bedford, Mark T.;James, Lindsey I.;Kireev, Dmitri B.;Frye, Stephen V.. And the article was included in Biochemistry in 2018.HPLC of Formula: 823-58-5 This article mentions the following:

Multivalent binding is an efficient means to enhance the affinity and specificity of chem. probes targeting multidomain proteins in order to study their function and role in disease. While the theory of multivalent binding is straightforward, phys. and structural characterization of bivalent binding encounters multiple tech. difficulties. We present a case study where a combination of exptl. techniques and computational simulations was used to comprehensively characterize the binding and structure-affinity relationships for a series of Bromosporine-based bivalent bromodomain ligands with a bivalent protein, Transcription Initiation Factor TFIID subunit 1 (TAF1). Exptl. techniques-Isothermal Titration Calorimetry, X-ray Crystallog., CD, Size Exclusion Chromatog.-Multi-Angle Light Scattering, and Surface Plasmon Resonance-were used to determine structures, binding affinities, and kinetics of monovalent ligands and bivalent ligands with varying linker lengths. The exptl. data for monomeric ligands were fed into explicit computational simulations, in which both ligand and protein species were present in a broad range of concentrations, and in up to a 100 s time regime, to match exptl. conditions. These simulations provided accurate estimates for apparent affinities (in good agreement with exptl. data), individual dissociation microconstants and other microscopic details for each type of protein-ligand complex. We conclude that the expected efficiency of bivalent ligands in a cellular context is difficult to estimate by a single technique in vitro, due to higher order associations favored at the concentrations used, and other complicating processes. Rather, a combination of structural, biophys., and computational approaches should be utilized to estimate and characterize multivalent interactions. In the experiment, the researchers used many compounds, for example, 4-Amino-3,6-dichloropyridazine (cas: 823-58-5HPLC of Formula: 823-58-5).

4-Amino-3,6-dichloropyridazine (cas: 823-58-5) belongs to pyridazine derivatives. Pyridazine-based compounds continued to be a great source of biologically active compounds as evidenced by the number of publications which emerged in 2021. The activity depends upon the changes of substituted groups in the pyridazine ring system resulting in different biological activities. In addition, the natural pyrimidine bases uracil, thymine, and cytosine, which are constituents of the nucleic acids, are found to be the most important naturally occurring diazines.HPLC of Formula: 823-58-5

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Chemical Proteomic Profiling of Bromodomains Enables the Wide-Spectrum Evaluation of Bromodomain Inhibitors in Living Cells was written by Li, Xin;Wu, Yizhe;Tian, Gaofei;Jiang, Yixiang;Liu, Zheng;Meng, Xianbin;Bao, Xiucong;Feng, Ling;Sun, Hongyan;Deng, Haiteng;Li, Xiang David. And the article was included in Journal of the American Chemical Society in 2019.Synthetic Route of C4H3Cl2N3 This article mentions the following:

Bromodomains, epigenetic “readers” of lysine acetylation marks, exist in different nuclear proteins with diverse biol. functions in chromatin biol. Malfunctions of bromodomains are associated with the pathogenesis of human diseases, such as cancer. Bromodomains have therefore emerged as therapeutic targets for drug discovery. Given the high structural similarity of bromodomains, a critical step in the development of bromodomain inhibitors is the evaluation of their selectivity to avoid off-target effects. While numerous bromodomain inhibitors have been identified, new methods to evaluate the inhibitor selectivity toward endogenous bromodomains in living cells remain needed. Here we report the development of a photoaffinity probe, photo-bromosporine (photo-BS), that enables the wide-spectrum profiling of bromodomain inhibitors in living cells. Photo-BS allowed light-induced crosslinking of recombinant bromodomains and endogenous bromodomain-containing proteins (BCPs) both in vitro and in living cells. The photo-BS-induced labeling of the bromodomains was selectively competed by the corresponding bromodomain inhibitors. Proteomics anal. revealed that photo-BS captured 28 out of the 42 known BCPs from the living cells. Assessment of the two bromodomain inhibitors, bromosporine and GSK6853, resulted in the identification of known as well as previously uncharacterized bromodomain targets. Collectively, we established a chem. proteomics platform to comprehensively evaluate bromodomain inhibitors in terms of their selectivity against endogenous BCPs in living cells. In the experiment, the researchers used many compounds, for example, 4-Amino-3,6-dichloropyridazine (cas: 823-58-5Synthetic Route of C4H3Cl2N3).

4-Amino-3,6-dichloropyridazine (cas: 823-58-5) belongs to pyridazine derivatives. Pyridazines are rare in nature, possibly reflecting the scarcity of naturally occurring hydrazines, common building blocks for the synthesis of these heterocycles. The unsubstituted pyridazines are more resistant to eletrophilic substitution due to the nature of withdrawal of electron density from the ring by two heteroatoms, while the related electron deficiency of the ring makes pyridazine more easily attacked by nucleophiles.Synthetic Route of C4H3Cl2N3

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Design, Synthesis, Crystallographic Studies, and Preliminary Biological Appraisal of New Substituted Triazolo[4,3-b]pyridazin-8-amine Derivatives as Tankyrase Inhibitors was written by Liscio, Paride;Carotti, Andrea;Asciutti, Stefania;Karlberg, Tobias;Bellocchi, Daniele;Llacuna, Laura;Macchiarulo, Antonio;Aaronson, Stuart A.;Schuler, Herwig;Pellicciari, Roberto;Camaioni, Emidio. And the article was included in Journal of Medicinal Chemistry in 2014.Electric Literature of C4H3Cl2N3 This article mentions the following:

Searching for selective tankyrases (TNKSs) inhibitors, a new small series of 6,8-disubstituted triazolo[4,3-b]pyridazines has been synthesized and characterized biol. Structure-based optimization of the starting hit compound N-(4-chlorophenyl)-6-methyl[1,2,4]triazolo[4,3-b]pyridazin-8-amine (NNL) prompted the authors to the discovery of 4-(2-(6-methyl-[1,2,4]triazolo[4,3-b]pyridazin-8-ylamino)ethyl)phenol (I), a low nanomolar selective TNKSs inhibitor working as NAD isostere as ascertained by crystallog. anal. Preliminary biol. data candidate this new class of derivatives as a powerful pharmacol. tools in the unraveling of TNKS implications in physiopathol. conditions. In the experiment, the researchers used many compounds, for example, 4-Amino-3,6-dichloropyridazine (cas: 823-58-5Electric Literature of C4H3Cl2N3).

4-Amino-3,6-dichloropyridazine (cas: 823-58-5) belongs to pyridazine derivatives. Pyridazines is a six-membered nitrogen-containing significant heterocycle. It has received considerable interest because of its useful applications as natural products, pharmaceuticals, and various bioactive molecules. Pyridazine compounds have attracted interest in various fields like medicinal, industrial, and agricultural research as they are used for numerous biological activities and other applications.Electric Literature of C4H3Cl2N3

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem