Tag: 349.7705

Bioactive phytoconstituents as potent inhibitors of casein kinase-2: dual implications in cancer and COVID-19 therapeutics was written by Anjum, Farah;Sulaimani, Nayab Md;Shafie, Alaa;Mohammad, Taj;Ashraf, Ghulam Md.;Bilgrami, Anwar L.;Alhumaydhi, Fahad A.;Alsagaby, Suliman A.;Yadav, Dharmendra Kumar;Hassan, Imtaiyaz Md.. And the article was included in RSC Advances in 2022.Product Details of 1009820-21-6 This article mentions the following:

Casein kinase 2 (CK2) is a conserved serine/threonine-protein kinase involved in hematopoietic cell survival, cell cycle control, DNA repair, and other cellular processes. It plays a significant role in cancer progression and viral infection. CK2 is considered a potential drug target in cancers and COVID-19 therapy. In this study, we have performed a virtual screening of phytoconstituents from the IMPPAT database to identify some potential inhibitors of CK2. The initial filter was the physicochem. properties of the mols. following the Lipinski rule of five. Then binding affinity calculation, PAINS filter, ADMET, and PASS analyses followed by interaction anal. were carried out to discover nontoxic and better hits. Finally, two compounds, stylopine and dehydroevodiamines with appreciable affinity and specific interaction towards CK2, were identified. Their time-evolution analyses were carried out using all-atom mol. dynamics simulation, principal component anal. and free energy landscape. Altogether, we propose that stylopine and dehydroevodiamines can be further explored in in vitro and in vivo settings to develop anticancer and antiviral therapeutics. In the experiment, the researchers used many compounds, for example, 5-((3-Chlorophenyl)amino)benzo[c][2,6]naphthyridine-8-carboxylic acid (cas: 1009820-21-6Product Details of 1009820-21-6).

5-((3-Chlorophenyl)amino)benzo[c][2,6]naphthyridine-8-carboxylic acid (cas: 1009820-21-6) belongs to naphthyridine derivatives. The naphthyridines have 10 delocalized π-electrons located in five molecular orbitals, each of which is distorted by the presence of the nitrogen atoms causing an electron drift in that direction. Halogen atoms attached to the naphthyridine moiety can be easily replaced by other nucleophiles such as alkoxides and amines.Product Details of 1009820-21-6

Referemce:
1,8-Naphthyridine – Wikipedia,
1,8-Naphthyridine | C8H6N2 – PubChem

Synergistic cytotoxic effects of bortezomib and CK2 inhibitor CX-4945 in acute lymphoblastic leukemia: turning off the prosurvival ER chaperone BIP/Grp78 and turning on the pro-apoptotic NF-κB. was written by Buontempo, Francesca;Orsini, Ester;Lonetti, Annalisa;Cappellini, Alessandra;Chiarini, Francesca;Evangelisti, Camilla;Evangelisti, Cecilia;Melchionda, Fraia;Pession, Andrea;Bertaina, Alice;Locatelli, Franco;Bertacchini, Jessika;Neri, Luca Maria;McCubrey, James A;Martelli, Alberto Maria. And the article was included in Oncotarget in 2016.Recommanded Product: 1009820-21-6 This article mentions the following:

The proteasome inhibitor bortezomib is a new targeted treatment option for refractory or relapsed acute lymphoblastic leukemia (ALL) patients. However, a limited efficacy of bortezomib alone has been reported. A terminal pro-apoptotic endoplasmic reticulum (ER) stress/unfolded protein response (UPR) is one of the several mechanisms of bortezomib-induced apoptosis. Recently, it has been documented that UPR disruption could be considered a selective anti-leukemia therapy. CX-4945, a potent casein kinase (CK) 2 inhibitor, has been found to induce apoptotic cell death in T-ALL preclinical models, via perturbation of ER/UPR pathway. In this study, we analyzed in T- and B-ALL preclinical settings, the molecular mechanisms of synergistic apoptotic effects observed after bortezomib/CX-4945 combined treatment. We demonstrated that, adding CX-4945 after bortezomib treatment, prevented leukemic cells from engaging a functional UPR in order to buffer the bortezomib-mediated proteotoxic stress in ER lumen. We documented that the combined treatment decreased pro-survival ER chaperon BIP/Grp78 expression, via reduction of chaperoning activity of Hsp90. Bortezomib/CX-4945 treatment inhibited NF-κB signaling in T-ALL cell lines and primary cells from T-ALL patients, but, intriguingly, in B-ALL cells the drug combination activated NF-κB p65 pro-apoptotic functions. In fact in B-cells, the combined treatment induced p65-HDAC1 association with consequent repression of the anti-apoptotic target genes, Bcl-xL and XIAP. Exposure to NEMO (IKKγ)-binding domain inhibitor peptide reduced the cytotoxic effects of bortezomib/CX-4945 treatment. Overall, our findings demonstrated that CK2 inhibition could be useful in combination with bortezomib as a novel therapeutic strategy in both T- and B-ALL. In the experiment, the researchers used many compounds, for example, 5-((3-Chlorophenyl)amino)benzo[c][2,6]naphthyridine-8-carboxylic acid (cas: 1009820-21-6Recommanded Product: 1009820-21-6).

5-((3-Chlorophenyl)amino)benzo[c][2,6]naphthyridine-8-carboxylic acid (cas: 1009820-21-6) belongs to naphthyridine derivatives. The naphthyridines have 10 delocalized π-electrons located in five molecular orbitals, each of which is distorted by the presence of the nitrogen atoms causing an electron drift in that direction. 1,6-Naphthyridine and some of its derivatives have been reported to have medicinal, electronic, and catalytic properties. But none of these investigations has yet resulted in any practical applications. Very few metal complexes of naphthyridines other than 1,8-naphthyridine have been described.Recommanded Product: 1009820-21-6

Referemce:
1,8-Naphthyridine – Wikipedia,
1,8-Naphthyridine | C8H6N2 – PubChem

X-ray Structures and Feasibility Assessment of CLK2 Inhibitors for Phelan-McDermid Syndrome was written by Kallen, Joerg;Bergsdorf, Christian;Arnaud, Bertrand;Bernhard, Mario;Brichet, Murielle;Cobos-Correa, Amanda;Elhajouji, Azeddine;Freuler, Felix;Galimberti, Ivan;Guibourdenche, Christel;Haenni, Simon;Holzinger, Sandra;Hunziker, Juerg;Izaac, Aude;Kaufmann, Markus;Leder, Lukas;Martus, Hans-Joerg;von Matt, Peter;Polyakov, Valery;Roethlisberger, Patrik;Roma, Guglielmo;Stiefl, Nikolaus;Uteng, Marianne;Lerchner, Andreas. And the article was included in ChemMedChem in 2018.Synthetic Route of C19H12ClN3O2 This article mentions the following:

CLK2 inhibition has been proposed as a potential mechanism to improve autism and neuronal functions in Phelan-McDermid syndrome (PMDS). Herein, the discovery of a very potent indazole CLK inhibitor series and the CLK2 x-ray structure of the most potent analog are reported. This new indazole series was identified through a biochem. CLK2 Caliper assay screen with 30k compounds selected by an in silico approach. Novel high-resolution x-ray structures of all CLKs, including the first CLK4 x-ray structure, bound to known CLK2 inhibitor tool compounds (e.g., TG003, CX-4945), are also shown and yield insight into inhibitor selectivity in the CLK family. The efficacy of the new CLK2 inhibitors from the indazole series was demonstrated in the mouse brain slice assay, and potential safety concerns were investigated. Genotoxicity findings in the human lymphocyte micronucleus test (MNT) assay are shown by using two structurally different CLK inhibitors to reveal a major concern for pan-CLK inhibition in PMDS. In the experiment, the researchers used many compounds, for example, 5-((3-Chlorophenyl)amino)benzo[c][2,6]naphthyridine-8-carboxylic acid (cas: 1009820-21-6Synthetic Route of C19H12ClN3O2).

5-((3-Chlorophenyl)amino)benzo[c][2,6]naphthyridine-8-carboxylic acid (cas: 1009820-21-6) belongs to naphthyridine derivatives. Functionalized naphthyridines and their benzo/heterofused analogs are present in numerous marine products and reported to possess wide-ranging activities such as antiproliferative, antiaggressive, and HIV-1 integrase inhibition in addition to their use as anti-HCV agents. 1,6-Naphthyridine and some of its derivatives have been reported to have medicinal, electronic, and catalytic properties. But none of these investigations has yet resulted in any practical applications.Synthetic Route of C19H12ClN3O2

Referemce:
1,8-Naphthyridine – Wikipedia,
1,8-Naphthyridine | C8H6N2 – PubChem

Intracellular protein kinase CK2 inhibition by ferulic acid-based trimodal nanodevice was written by Zanin, Sofia;Molinari, Simone;Cozza, Giorgio;Magro, Massimiliano;Fedele, Giorgio;Vianello, Fabio;Venerando, Andrea. And the article was included in International Journal of Biological Macromolecules in 2020.HPLC of Formula: 1009820-21-6 This article mentions the following:

Protein kinase CK2, a pleiotropic and constitutively active kinase, is strictly involved in different diseases, especially in cancer. Many efforts have been carried out to develop specific CK2 inhibitors and recently, it has been evidenced that ferulic acid (FA) represents a promising, albeit cell impermeable, CK2 inhibitor. In the present study, the potential of a nanotechnol. approach to cope with intracellular CK2 regulation was explored. Surface-Active Maghemite Nanoparticles (SAMNs), coupling magnetism with photoluminescence, a new feature of SAMNs here described for the first time, were chosen as dual imaging nanocarrier for FA. The self-assembled nanodevice (SAMN@FA) displayed a significant CK2 inhibitory activity in vitro. Moreover, effective cellular internalization of SAMN@FA in cancer cells was proved by direct visualization of the photoluminescent nanocarrier by confocal microscopy and was corroborated by phosphorylation levels of endogenous CK2 targets. The proposed trimodal nanodevice, representing the first example of cellular CK2 nano-inhibition, paves the way for novel active nanocarriers as appealing theranostic tool for future biomedical applications. In the experiment, the researchers used many compounds, for example, 5-((3-Chlorophenyl)amino)benzo[c][2,6]naphthyridine-8-carboxylic acid (cas: 1009820-21-6HPLC of Formula: 1009820-21-6).

5-((3-Chlorophenyl)amino)benzo[c][2,6]naphthyridine-8-carboxylic acid (cas: 1009820-21-6) belongs to naphthyridine derivatives. The naphthyridines have 10 delocalized π-electrons located in five molecular orbitals, each of which is distorted by the presence of the nitrogen atoms causing an electron drift in that direction. 1,6-Naphthyridine and some of its derivatives have been reported to have medicinal, electronic, and catalytic properties. But none of these investigations has yet resulted in any practical applications.HPLC of Formula: 1009820-21-6

Referemce:
1,8-Naphthyridine – Wikipedia,
1,8-Naphthyridine | C8H6N2 – PubChem

Activating Transcription Factor 6 Mediates Inflammatory Signals in Intestinal Epithelial Cells Upon Endoplasmic Reticulum Stress was written by Stengel, Stephanie T.;Fazio, Antonella;Lipinski, Simone;Jahn, Martin T.;Aden, Konrad;Ito, Go;Wottawa, Felix;Kuiper, Jan W. P.;Coleman, Olivia I.;Tran, Florian;Bordoni, Dora;Bernardes, Joana P.;Jentzsch, Marlene;Luzius, Anne;Bierwirth, Sandra;Messner, Berith;Henning, Anna;Welz, Lina;Kakavand, Nassim;Falk-Paulsen, Maren;Imm, Simon;Hinrichsen, Finn;Zilbauer, Matthias;Schreiber, Stefan;Kaser, Arthur;Blumberg, Richard;Haller, Dirk;Rosenstiel, Philip. And the article was included in Gastroenterology in 2020.Product Details of 1009820-21-6 This article mentions the following:

Excess and unresolved endoplasmic reticulum (ER) stress in intestinal epithelial cells (IECs) promotes intestinal inflammation. Activating transcription factor 6 (ATF6) is one of the signaling mediators of ER stress. We studied the pathways that regulate ATF6 and its role for inflammation in IECs. We performed an RNA interference screen, using 23,349 unique small interfering RNAs targeting 7783 genes and a luciferase reporter controlled by an ATF6-dependent ERSE (ER stress-response element) promoter, to identify proteins that activate or inhibit the ATF6 signaling pathway in HEK293 cells. To validate the screening results, intestinal epithelial cell lines (Caco-2 cells) were transfected with small interfering RNAs or with a plasmid overexpressing a constitutively active form of ATF6. Caco-2 cells with a CRISPR-mediated disruption of autophagy related 16 like 1 gene (ATG16L1) were used to study the effect of ATF6 on ER stress in autophagy-deficient cells. We also studied intestinal organoids derived from mice that overexpress constitutively active ATF6, from mice with deletion of the autophagy related 16 like 1 or X-Box binding protein 1 gene in IECs (Atg16l1ΔIEC or Xbp1ΔIEC, which both develop spontaneous ileitis), from patients with Crohn’s disease (CD) and healthy individuals (controls). Cells and organoids were incubated with tunicamycin to induce ER stress and/or chem. inhibitors of newly identified activator proteins of ATF6 signaling, and analyzed by real-time polymerase chain reaction and immunoblots. Atg16l1ΔIEC and control (Atg16l1fl/fl) mice were given i.p. injections of tunicamycin and were treated with chem. inhibitors of ATF6 activating proteins. We identified and validated 15 suppressors and 7 activators of the ATF6 signaling pathway; activators included the regulatory subunit of casein kinase 2 (CSNK2B) and acyl-CoA synthetase long chain family member 1 (ACSL1). Knockdown or chem. inhibition of CSNK2B and ACSL1 in Caco-2 cells reduced activity of the ATF6-dependent ERSE reporter gene, diminished transcription of the ATF6 target genes HSP90B1 and HSPA5 and reduced NF-κB reporter gene activation on tunicamycin stimulation. Atg16l1ΔIEC and or Xbp1ΔIEC organoids showed increased expression of ATF6 and its target genes. Inhibitors of ACSL1 or CSNK2B prevented activation of ATF6 and reduced CXCL1 and tumor necrosis factor (TNF) expression in these organoids on induction of ER stress with tunicamycin. Injection of mice with inhibitors of ACSL1 or CSNK2B significantly reduced tunicamycin-mediated intestinal inflammation and IEC death and expression of CXCL1 and TNF in Atg16l1ΔIEC mice. Purified ileal IECs from patients with CD had higher levels of ATF6, CSNK2B, and HSPA5 mRNAs than controls; early-passage organoids from patients with active CD show increased levels of activated ATF6 protein, incubation of these organoids with inhibitors of ACSL1 or CSNK2B reduced transcription of ATF6 target genes, including TNF. Ileal IECs from patients with CD have higher levels of activated ATF6, which is regulated by CSNK2B and HSPA5. ATF6 increases expression of TNF and other inflammatory cytokines in response to ER stress in these cells and in organoids from Atg16l1ΔIEC and Xbp1ΔIEC mice. Strategies to inhibit the ATF6 signaling pathway might be developed for treatment of inflammatory bowel diseases. In the experiment, the researchers used many compounds, for example, 5-((3-Chlorophenyl)amino)benzo[c][2,6]naphthyridine-8-carboxylic acid (cas: 1009820-21-6Product Details of 1009820-21-6).

5-((3-Chlorophenyl)amino)benzo[c][2,6]naphthyridine-8-carboxylic acid (cas: 1009820-21-6) belongs to naphthyridine derivatives. The naphthyridines have 10 delocalized π-electrons located in five molecular orbitals, each of which is distorted by the presence of the nitrogen atoms causing an electron drift in that direction. Halogen atoms attached to the naphthyridine moiety can be easily replaced by other nucleophiles such as alkoxides and amines.Product Details of 1009820-21-6

Referemce:
1,8-Naphthyridine – Wikipedia,
1,8-Naphthyridine | C8H6N2 – PubChem

CK2 inhibition with silmitasertib promotes methuosis-like cell death associated to catastrophic massive vacuolization of colorectal cancer cells was written by Silva-Pavez, Eduardo;Villar, Paulina;Trigo, Cesar;Caamano, Esteban;Niechi, Ignacio;Perez, Pablo;Munoz, Juan P.;Aguayo, Francisco;Burzio, Veronica A.;Varas-Godoy, Manuel;Castro, Ariel F.;Colombo, Maria I.;Tapia, Julio C.. And the article was included in Cell Death & Disease in 2019.Safety of 5-((3-Chlorophenyl)amino)benzo[c][2,6]naphthyridine-8-carboxylic acid This article mentions the following:

Protein kinase CK2 is a highly conserved and constitutively active Ser/Thr-kinase that phosphorylates a large number of substrates, resulting in increased cell proliferation and survival. A known target of CK2 is Akt, a player in the PI3K/Akt/mTORC1 signaling pathway, which is aberrantly activated in 32% of colorectal cancer (CRC) patients. On the other hand, mTORC1 plays an important role in the regulation of protein synthesis, cell growth, and autophagy. Some studies suggest that CK2 regulates mTORC1 in several cancers. The most recently developed CK2 inhibitor, silmitasertib (formerly CX-4945), has been tested in phase I/II trials for cholangiocarcinoma and multiple myeloma. This drug has been shown to induce autophagy and enhance apoptosis in pancreatic cancer cells and to promote apoptosis in non-small cell lung cancer cells. Nevertheless, it has not been tested in studies for CRC patients. We show in this work that inhibition of CK2 with silmitasertib decreases in vitro tumorigenesis of CRC cells in response to G2/M arrest, which correlates with mTORC1 inhibition and formation of large cytoplasmic vacuoles. Notably, mol. markers indicate that these vacuoles derive from massive macropinocytosis. Altogether, these findings suggest that an aberrantly elevated expression/activity of CK2 may play a key role in CRC, promoting cell viability and proliferation in untreated cells, however, its inhibition with silmitasertib promotes methuosis-like cell death associated to massive catastrophic vacuolization, accounting for decreased tumorigenicity at later times. These characteristics of silmitasertib support a potential therapeutic use in CRC patients and probably other CK2-dependent cancers. In the experiment, the researchers used many compounds, for example, 5-((3-Chlorophenyl)amino)benzo[c][2,6]naphthyridine-8-carboxylic acid (cas: 1009820-21-6Safety of 5-((3-Chlorophenyl)amino)benzo[c][2,6]naphthyridine-8-carboxylic acid).

5-((3-Chlorophenyl)amino)benzo[c][2,6]naphthyridine-8-carboxylic acid (cas: 1009820-21-6) belongs to naphthyridine derivatives. Heterocyclic nitrogen compounds, including fused 1,5-naphthyridines, have versatile applications in synthetic organic chemistry and play an important role in the field of medicinal chemistry, as many of them have a wide range of biological activities. Imidazonaphthyridines have been prepared through a ‘one-pot’ three-component ‘domino’ reaction between the keto-ester, acrolein, and ethylenediamine in presence of 4 Å molecular sieves. The corresponding thiazolonaphthyridine is obtained from a similar reaction using 2-aminoethanethiol and Dowex basic anion-exchange resin.Safety of 5-((3-Chlorophenyl)amino)benzo[c][2,6]naphthyridine-8-carboxylic acid

Referemce:
1,8-Naphthyridine – Wikipedia,
1,8-Naphthyridine | C8H6N2 – PubChem