Day: January 5, 2023

Small Molecule Dysregulation of TEAD Lipidation Induces a Dominant-Negative Inhibition of Hippo Pathway Signaling was written by Holden, Jeffrey K.;Crawford, James J.;Noland, Cameron L.;Schmidt, Stephen;Zbieg, Jason R.;Lacap, Jennifer A.;Zang, Richard;Miller, Gregory M.;Zhang, Yue;Beroza, Paul;Reja, Rohit;Lee, Wendy;Tom, Jeffrey Y. K.;Fong, Rina;Steffek, Micah;Clausen, Saundra;Hagenbeek, Thjis J.;Hu, Taishan;Zhou, Zheng;Shen, Hong C.;Cunningham, Christian N.. And the article was included in Cell Reports in 2020.Quality Control of 1H-Benzo[d][1,2,3]triazol-1-amine This article mentions the following:

The transcriptional enhanced associate domain (TEAD) family of transcription factors serves as the receptors for the downstream effectors of the Hippo pathway, YAP and TAZ, to upregulate the expression of multiple genes involved in cellular proliferation and survival. Recent work identified TEAD S-palmitoylation as critical for protein stability and activity as the lipid tail extends into a hydrophobic core of the protein. Here, we report the identification and characterization of a potent small mol. that binds the TEAD lipid pocket (LP) and disrupts TEAD S-palmitoylation. Using a variety of biochem., structural, and cellular methods, we uncover that TEAD S-palmitoylation functions as a TEAD homeostatic protein level checkpoint and that dysregulation of this lipidation affects TEAD transcriptional activity in a dominant-neg. manner. Furthermore, we demonstrate that targeting the TEAD LP is a promising therapeutic strategy for modulating the Hippo pathway, showing tumor stasis in a mouse xenograft model. In the experiment, the researchers used many compounds, for example, 1H-Benzo[d][1,2,3]triazol-1-amine (cas: 1614-12-6Quality Control of 1H-Benzo[d][1,2,3]triazol-1-amine).

1H-Benzo[d][1,2,3]triazol-1-amine (cas: 1614-12-6) belongs to triazole derivatives. Among the nitrogen-containing heterocyclic compounds, triazoles emerge with superior pharmacological applications. The presence of the three nitrogen atoms in triazole structures afforded opportunities for a plethora of structural modification with the generation of novel therapeutically potential agents, which is different from other heterocyclic compounds.Quality Control of 1H-Benzo[d][1,2,3]triazol-1-amine

Referemce:
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

Structure and biological activity of a binuclear Co(II) complex [Co₂(Htda)₂(H₂O)₆·5 H₂O] was written by Li, Jian-jun;Li, Mei-yu;Gao, En-jun;Shen, Guang-hai. And the article was included in Shenyang Huagong Daxue Xuebao in 2014.Application In Synthesis of 1H-1,2,3-Triazole-4,5-dicarboxylic acid This article mentions the following:

The complex [Co₂(Htda)₂(H₂O)₆·5H₂O] (H₃tda = 1H-1,2,3-triazole-4,5-dicarboxylic acid) was synthesized by hydrothermal method and characterized by x-ray anal. The binding of the title complex with calf thymus DNA (CT-DNA) was studied by fluorescence spectra. Gel electrophoresis assay and the optical d. scanning experiment demonstrated the ability to cleave the pBR322 DNA of the complex. In the experiment, the researchers used many compounds, for example, 1H-1,2,3-Triazole-4,5-dicarboxylic acid (cas: 4546-95-6Application In Synthesis of 1H-1,2,3-Triazole-4,5-dicarboxylic acid).

1H-1,2,3-Triazole-4,5-dicarboxylic acid (cas: 4546-95-6) belongs to triazole derivatives. The triazole ring is a relatively stable functional group, and the triazole bond can be used for a variety of applications, such as replacing the phosphate backbone of DNA. The presence of the three nitrogen atoms in triazole structures afforded opportunities for a plethora of structural modification with the generation of novel therapeutically potential agents, which is different from other heterocyclic compounds.Application In Synthesis of 1H-1,2,3-Triazole-4,5-dicarboxylic acid

Referemce:
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

Mechanistic studies of cytochrome P450 3A4 time-dependent inhibition using two cysteine-targeting electrophiles was written by Barr, John T.;Wang, Zhican;Min, Xiaoshan;Wienkers, Henry J.;Rock, Brooke M.;Rock, Dan A.;Wienkers, Larry C.. And the article was included in Drug Metabolism & Disposition in 2020.Electric Literature of C6H6N4 This article mentions the following:

Experiments designed to identify the mechanism of cytochrome P 450 inactivation are critical to drug discovery. Small mols. irreversibly inhibit P 450 enzymic activity via two primary mechanisms: apoprotein adduct formation or heme modification. Understanding the interplay between chem. structures of reactive electrophiles and the impact on CYP3A4 structure and function can ultimately provide insights into drug design to minimize P 450 inactivation. The compound’s effect on (1) enzymic activity, (2) carbon monoxide (CO) binding capacity, (3) intact heme content, and (4) protein conformation were measured. Results showed that PM had a large time-dependent loss of enzyme activity, whereas PIA did not. The differential effect on enzymic activity between PM and PIA was mirrored in the CO binding data. Despite disruption of CO binding, neither compound affected the heme concentrations, inferring there was no destruction or alkylation of the heme. Lastly, differential scanning fluorescence showed PM-treated CYP3A4 caused a shift in the onset temperature required to induce protein aggregation, which was not observed for CYP3A4 treated with PIA. In conclusion, alkylation of CYP3A4 apoprotein can have a variable impact on catalytic activity, CO binding, and protein conformation that may be compound-dependent. These results highlight the need for careful interpretation of exptl. results aimed at characterizing the nature of P 450 enzyme inactivation. In the experiment, the researchers used many compounds, for example, 1H-Benzo[d][1,2,3]triazol-1-amine (cas: 1614-12-6Electric Literature of C6H6N4).

1H-Benzo[d][1,2,3]triazol-1-amine (cas: 1614-12-6) belongs to triazole derivatives. The many free lone pairs in triazoles make them useful as coordination compounds, although not typically as haptic ligands.Triazole heterocyclic structures are found to form many weak nonbond interactions with the receptors and enzymes in biological systems.Electric Literature of C6H6N4

Referemce:
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

A simplified approach to N- and N,N’-linked 1,2,4-triazoles by transamination was written by Naik, Anil D.;Marchand-Brynaert, Jacqueline;Garcia, Yann. And the article was included in Synthesis in 2008.Application In Synthesis of 4-(4H-1,2,4-Triazol-4-yl)benzoic acid This article mentions the following:

A facile one-step procedure for the preparation of 4,4′-bis-1,2,4-triazole is reported. Direct transamination of N,N-dimethylformamide azine dihydrochloride by heating with 4-amino-1,2,4-triazole in refluxing benzene readily yields the target mol. in short duration of time with significant yield (73%). This catalyst-free method was extended to synthesize a series of 4-substituted 1,2,4-triazoles of potential interest in coordination chem. In the experiment, the researchers used many compounds, for example, 4-(4H-1,2,4-Triazol-4-yl)benzoic acid (cas: 157069-48-2Application In Synthesis of 4-(4H-1,2,4-Triazol-4-yl)benzoic acid).

4-(4H-1,2,4-Triazol-4-yl)benzoic acid (cas: 157069-48-2) belongs to triazole derivatives. Among the nitrogen-containing heterocyclic compounds, triazoles emerge with superior pharmacological applications.Triazole heterocyclic structures are found to form many weak nonbond interactions with the receptors and enzymes in biological systems.Application In Synthesis of 4-(4H-1,2,4-Triazol-4-yl)benzoic acid

Referemce:
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

Synthesis and photochemical decomposition of some substituted 1,2-, 1,2,3- and 1,2,4-azafulfenes was written by Burgess, Edward M.;Sanchez, Joseph P.. And the article was included in Journal of Organic Chemistry in 1974.Synthetic Route of C5H7N3O2 This article mentions the following:

A series of phenylpyrazole and -triazole diphenylcarbinols have been converted to the hydrochloride salts of the carbinyl chlorides and thence to the corresponding azafulvenes by dehydrohalogenation with triethylamine at -78°. Irradiation of the triazafulvenes at this temperature gave a mixture of isolable products which implicate azatriafulvene and azete as possible unstable precursors. The latter intermediate may also be involved in the photochem. decomposition of triphenyltriazine which was also examined The diazafulvenes prepared proved isolable but photochem. inert. In the experiment, the researchers used many compounds, for example, Ethyl 1H-1,2,3-triazole-5-carboxylate (cas: 40594-98-7Synthetic Route of C5H7N3O2).

Ethyl 1H-1,2,3-triazole-5-carboxylate (cas: 40594-98-7) belongs to triazole derivatives. Triazoles consist of a five-membered ring containing three nitrogen atoms and are biologically active, especially as antifungal, antimicrobial and enzyme inhibitors. Many triazoles have antifungal effects: the triazole antifungal drugs include fluconazole, isavuconazole, itraconazole, voriconazole, pramiconazole, ravuconazole, and posaconazole and triazole plant-protection fungicides include epoxiconazole, triadimenol, myclobutanil, propiconazole, prothioconazole, metconazole, cyproconazole, tebuconazole, flusilazole and paclobutrazol.Synthetic Route of C5H7N3O2

Referemce:
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

A dinuclear Ni(II) complex [Ni₂ (Htda)₂ (H₂O)₆]·4H₂O: interaction with DNA and apoptosis studies was written by Wu, Guang-lei;Zhan, Lin;Xu, Jin;Gao, En-jun. And the article was included in Shenyang Huagong Daxue Xuebao in 2012.Quality Control of 1H-1,2,3-Triazole-4,5-dicarboxylic acid This article mentions the following:

The interaction of the Ni (II) complex [Ni₂ (Htda)₂ (H₂O)₆]·4H₂O (Htda=1,2,3-triazole-4,5-dicarboxylic acid acisamples) with DNA has been explored by electronic absorption spectroscopy, emission spectroscopy and gel electrophoretic assay. The results show that the modes of the interaction between complex and DNA are mainly electrostatic interaction and intercalation. Further more, the apoptotic tests indicate that the complexes have an apoptotic effect on HeLa cells. In the experiment, the researchers used many compounds, for example, 1H-1,2,3-Triazole-4,5-dicarboxylic acid (cas: 4546-95-6Quality Control of 1H-1,2,3-Triazole-4,5-dicarboxylic acid).

1H-1,2,3-Triazole-4,5-dicarboxylic acid (cas: 4546-95-6) belongs to triazole derivatives. Triazoles are important five-member nitrogen heterocycles involved in a wide range of industrial applications such as agrochemicals, corrosion inhibitors, dyes, optical brighteners, as well as biologically active agents. Triazole growth retardants such as uniconazole and paclobutrazol have been known to inhibit the biosynthesis of gibberellins by blocking kaurene oxidase, an P450 enzymeQuality Control of 1H-1,2,3-Triazole-4,5-dicarboxylic acid

Referemce:
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

Evaluation of diuron tolerance and biotransformation by the white-rot fungus Ganoderma lucidum was written by Coelho-Moreira, Jaqueline da Silva;Brugnari, Tatiane;Sa-Nakanishi, Anacharis B.;Castoldi, Rafael;de Souza, Cristina G. M.;Bracht, Adelar;Peralta, Rosane M.. And the article was included in Fungal Biology in 2018.Related Products of 1614-12-6 This article mentions the following:

The white rot basidiomycete Ganoderma lucidum was evaluated for its capability to tolerate and to degrade the herbicide diuron. Diuron at a subtoxic concentration was added at the start of the cultivation in glucose liquid stationary cultures. Under this condition diuron was a laccase inducer. Almost 50% of the initially present diuron was removed after 15 d of cultivation. Two diuron metabolites were found N′-(3,4-dichlorophenyl)-N-methylurea (DCPMU) and 3,4-dichlorophenylurea (DCPU). The addition of the cytochrome P 450 inhibitors 1-aminobenzotriazole and piperonyl butoxide reduced significantly the capability of the fungus in degrading diuron. The activities of superoxide dismutase and catalase were significantly increased in the mycelial extracts by the presence of diuron. On the other hand, diuron did not cause any significant alteration in the levels of reactive oxygen species. Addnl., laccase could also degrade diuron in vitro and this degradation was increased by the addition of synthetic mediators, 3-ethylbenzthiazoline-6-sulfonic acid and acetylacetone. Significant reduction in the toxicity, as evaluated by the Lactuca sativa bioassay, was observed after G. lucidum treatment. In conclusion, G. lucidum is able to metabolize diuron by intra- and extracellular mechanisms, without the accumulation of toxic products. In the experiment, the researchers used many compounds, for example, 1H-Benzo[d][1,2,3]triazol-1-amine (cas: 1614-12-6Related Products of 1614-12-6).

1H-Benzo[d][1,2,3]triazol-1-amine (cas: 1614-12-6) belongs to triazole derivatives. However, triazoles are also useful in bioorthogonal chemistry, because the large number of nitrogen atoms causes triazoles to react similar to azides. Both the triazoles and their derivatives have significant biological properties including antimicrobial, antiviral, antitubercular, anticancer, anticonvulsant, analgesic, antioxidant, anti-inflammatory, and antidepressant activities.Related Products of 1614-12-6

Referemce:
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

The preparation of 7- and 9-glucopyranosyl and -xylopyranosyl derivatives of 8-azaxanthine (5,7-dihydroxy-v-triazolo[d]pyrimidine) was written by Baddiley, J.;Buchanan, J. G.;Osborne, G. O.. And the article was included in Journal of the Chemical Society in 1958.Quality Control of 1H-1,2,3-Triazole-4,5-dicarboxylic acid This article mentions the following:

2,3,4,6-Tetra-O-acetyl-β-D-glucopyranosyl azide heated under reflux 2.5 hrs., with MeO₂CCCCO₂Me gave 96% di-Me 1-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)-1,2,3-triazole-4,5-dicarboxylate (I), m. 153°. I treated at 0° overnight with dry MeOH saturated with NH₃ gave colorless crystals of indeterminate m.p. of 1-β-D-glucopyranosyl-1,2,3-triazole-4,5-dicarboxamide (II). Di-Me 1-(2,3,4-tri-O-acetyl-β-D-xylopyranosyl)-1,2,3-triazole-4,5-dicarboxylate (III), prepared as above from 2,3,4-tri-O-acetyl-β-D-xylopyranosyl azide, m. 114°; diamide (IV), colorless crystals, no m.p. given. Acid hydrolysis of triazole derivatives gave as initial decomposition products the parent sugars and a base, presumably 1,2,3-triazole-4,5-dicarboxamide; further hydrolysis led to a monamide and finally to 1,2,3-triazole-4,5-dicarboxylic acid, m. 198°. The action of KBrO on IV led to two fractions, containing components A and B, after separation using a Dowex-2 resin column. Component A was found to be 7-β-D-xylopyranosyl-8-azaxanthine and B was 9-β-D-xylopyranosyl-8-azaxanthine. Similarly KBrO with II yielded 7-β-D-glucopyranosyl-8-azaxanthine and 9-β-D-glucopyranosyl-8-azaxanthine. After hydrolysis with N HCl for 1 hr. at 95° both 7-glycosyl and the 9-xylosyl derivatives were hydrolyzed to the parent sugars and 8-azaxanthine. The 9-glucosyl derivative required 2 hrs. at 95°. 5-Amino-1-methyl-1,2,3-triazole-4-carboxamide (V), prepared from NCCH₂CONH₂ and MeN₃ in EtOH in the presence of Na, m. 248° (EtOH). V fused with urea 2.5 hrs. at 170-80° followed by purification using a Dowex-2 resin column gave 9-methyl-8-azaxanthine, needles, m. 320° (decomposition) (H₂O). In the experiment, the researchers used many compounds, for example, 1H-1,2,3-Triazole-4,5-dicarboxylic acid (cas: 4546-95-6Quality Control of 1H-1,2,3-Triazole-4,5-dicarboxylic acid).

1H-1,2,3-Triazole-4,5-dicarboxylic acid (cas: 4546-95-6) belongs to triazole derivatives. The many free lone pairs in triazoles make them useful as coordination compounds, although not typically as haptic ligands.Triazole heterocyclic structures are found to form many weak nonbond interactions with the receptors and enzymes in biological systems.Quality Control of 1H-1,2,3-Triazole-4,5-dicarboxylic acid

Referemce:
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

Development of a Potent Brain-Penetrant EGFR Tyrosine Kinase Inhibitor against Malignant Brain Tumors was written by Tsang, Jonathan E.;Urner, Lorenz M.;Kim, Gyudong;Chow, Kingsley;Baufeld, Lynn;Faull, Kym;Cloughesy, Timothy F.;Clark, Peter M.;Jung, Michael E.;Nathanson, David A.. And the article was included in ACS Medicinal Chemistry Letters in 2020.Reference of 1614-12-6 This article mentions the following:

The epidermal growth factor receptor (EGFR) is genetically altered in nearly 60% of glioblastoma tumors; however, tyrosine kinase inhibitors (TKIs) against EGFR have failed to show efficacy for patients with these lethal brain tumors. This failure is attributed to the inability of clin. tested EGFR TKIs to cross the blood-brain barrier (BBB) and achieve adequate pharmacol. levels to inhibit various oncogenic forms of EGFR that drive glioblastoma. Through SAR anal., we developed compound 5 (JCN037)(I) from an anilinoquinazoline scaffold by ring fusion of the 6,7-dialkoxy groups to reduce the number of rotatable bonds and polar surface area and by introduction of an ortho-fluorine and meta-bromine on the aniline ring for improved potency and BBB penetration. Relative to the conventional EGFR TKIs erlotinib and lapatinib, JCN037 displayed potent activity against EGFR amplified/mutant patient-derived cell cultures, significant BBB penetration (2:1 brain-to-plasma ratio), and superior efficacy in an EGFR-driven orthotopic glioblastoma xenograft model. In the experiment, the researchers used many compounds, for example, 1H-Benzo[d][1,2,3]triazol-1-amine (cas: 1614-12-6Reference of 1614-12-6).

1H-Benzo[d][1,2,3]triazol-1-amine (cas: 1614-12-6) belongs to triazole derivatives. Triazoles are important five-member nitrogen heterocycles involved in a wide range of industrial applications such as agrochemicals, corrosion inhibitors, dyes, optical brighteners, as well as biologically active agents. Many triazoles have antifungal effects: the triazole antifungal drugs include fluconazole, isavuconazole, itraconazole, voriconazole, pramiconazole, ravuconazole, and posaconazole and triazole plant-protection fungicides include epoxiconazole, triadimenol, myclobutanil, propiconazole, prothioconazole, metconazole, cyproconazole, tebuconazole, flusilazole and paclobutrazol.Reference of 1614-12-6

Referemce:
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics

Efficacy of novel pyrazolone phosphodiesterase inhibitors in experimental mouse models of Trypanosoma cruzi was written by Siciliano de Araujo, Julianna;da Silva, Cristiane Franca;da Gama Jaen Batista, Denise;Nefertiti, Aline;Ferreira de Almeida Fiuza, Ludmila;Fonseca-Berzal, Cristina Rosa;da Silva, Patricia Bernardino;Batista, Marcos Meuser;Sijm, Maarten;Kalejaiye, Titilola D.;de Koning, Harry P.;Maes, Louis;Sterk, Geert Jan;Leurs, Rob;de Nazare Correia Soeiro, Maria. And the article was included in Antimicrobial Agents and Chemotherapy in 2020.Recommanded Product: 1614-12-6 This article mentions the following:

Pyrazolones are heterocyclic compounds with interesting biol. properties. Some derivatives inhibit phosphodiesterases (PDEs) and thereby increase the cellular concentration of cAMP (cAMP), which plays a vital role in the control of metabolism in eukaryotic cells, including the protozoan Trypanosoma cruzi, the etiol. agent of Chagas disease (CD), a major neglected tropical disease. In vitro phenotypic screening identified a 4-bromophenyl-dihydropyrazole dimer as an anti-T. cruzi hit and 17 novel pyrazolone analogs with variations on the Ph ring were investigated in a panel of phenotypic laboratory models. Potent activity against the intracellular forms (Tulahuen and Y strains) was obtained with 50% effective concentration (EC₅₀) values within the 0.17 to 3.3μM range. Although most were not active against bloodstream trypomastigotes, an altered morphol. and loss of infectivity were observed Pretreatment of the mammalian host cells with pyrazolones did not interfere with infection and proliferation, showing that the drug activity was not the result of changes to host cell metabolism The pyrazolone NPD-227 increased the intracellular cAMP levels and was able to sterilize T. cruzi-infected cell cultures. Thus, due to its high potency and selectivity in vitro, and its additive interaction with benznidazole (Bz), NPD-227 was next assessed in the acute mouse model. Oral dosing for 5 days of NPD-227 at 10 mg/kg + Bz at 10 mg/kg not only reduced parasitemia (>87%) but also protected against mortality (>83% survival), hence demonstrating superiority to the monotherapy schemes. These data support these pyrazolone mols. as potential novel therapeutic alternatives for Chagas disease. In the experiment, the researchers used many compounds, for example, 1H-Benzo[d][1,2,3]triazol-1-amine (cas: 1614-12-6Recommanded Product: 1614-12-6).

1H-Benzo[d][1,2,3]triazol-1-amine (cas: 1614-12-6) belongs to triazole derivatives. Triazoles consist of a five-membered ring containing three nitrogen atoms and are biologically active, especially as antifungal, antimicrobial and enzyme inhibitors. Triazoles are compounds with a vast spectrum of applications, varying from materials (polymers), agricultural chemicals, pharmaceuticals, photoactive chemicals and dyes.Recommanded Product: 1614-12-6

Referemce:
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics