Month: February 2023

Improved metabolite characterization by liquid chromatography – Tandem mass spectrometry through electron impact type fragments from adduct ions was written by Ducati, Anita O.;Ruskic, David;Sosnowski, Piotr;Baba, Takashi;Bonner, Ron;Hopfgartner, Gerard. And the article was included in Analytica Chimica Acta in 2021.Related Products of 42971-09-5 This article mentions the following:

Using a chimeric collision cell mounted on a quadrupole time-of-flight platform, collision induced dissociation (CID) and electron induced dissociation (EID) were investigated for the LC-MS anal. of low mol. weight compounds including drugs and endogenous metabolites. Compared to CID, EID fragmentation of the [M+H]⁺ species (10-20 eV) from standard compounds resulted in addnl. specific and informative fragments, mostly due to neutral losses and, in some cases due to ring openings. Some analytes, for example reserpine and vinpocetine, provided characteristic [M+H]^•2+ species. For most analytes for sodium and potassium adducts and multimers a radical cation M^•+ and electron impact type fragments were observed in the EID spectra, providing the opportunity to use EI libraries to support metabolite identification. EID opens the possibility to get structural information from adduct ions which is often not the case with CID. EID enabled the putative characterization of two metabolites in rat urine as glucuronides of 5,6-dihydroxyindole based on EID fragmentation of the potassium adducts. In the experiment, the researchers used many compounds, for example, (41S,13aS)-Ethyl 13a-ethyl-2,3,41,5,6,13a-hexahydro-1H-indolo[3,2,1-de]pyrido[3,2,1-ij][1,5]naphthyridine-12-carboxylate (cas: 42971-09-5Related Products of 42971-09-5).

(41S,13aS)-Ethyl 13a-ethyl-2,3,41,5,6,13a-hexahydro-1H-indolo[3,2,1-de]pyrido[3,2,1-ij][1,5]naphthyridine-12-carboxylate (cas: 42971-09-5) belongs to naphthyridine derivatives. The naphthyridine ring system, being very π-deficient, is highly vulnerable towards nucleophilic attack, and consequently there has been extensive investigation of reactions involving nitrogen nucleophiles. 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.Related Products of 42971-09-5

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

2-Formylpyridyl Ureas as Highly Selective Reversible-Covalent Inhibitors of Fibroblast Growth Factor Receptor 4 was written by Knoepfel, Thomas;Furet, Pascal;Mah, Robert;Buschmann, Nicole;Leblanc, Catherine;Ripoche, Sebastien;Graus-Porta, Diana;Wartmann, Markus;Galuba, Inga;Fairhurst, Robin A.. And the article was included in ACS Medicinal Chemistry Letters in 2018.Name: 7-(Dimethoxymethyl)-1,2,3,4-tetrahydro-1,8-naphthyridine This article mentions the following:

As part of a project to identify FGFR4 selective inhibitors, scaffold morphing of a 2-formylquinoline amide hit identified series of 2-formylpyridine ureas (2-FPUs) with improved potency and physicochem. properties. In particular, tetrahydronaphthyridine urea analogs with cellular activities below 30 nM have been identified. Consistent with the hypothesized reversible-covalent mechanism of inhibition, the 2-FPUs exhibited slow binding kinetics, and the aldehyde, as the putative electrophile, could be demonstrated to be a key structural element for activity. In the experiment, the researchers used many compounds, for example, 7-(Dimethoxymethyl)-1,2,3,4-tetrahydro-1,8-naphthyridine (cas: 204452-91-5Name: 7-(Dimethoxymethyl)-1,2,3,4-tetrahydro-1,8-naphthyridine).

7-(Dimethoxymethyl)-1,2,3,4-tetrahydro-1,8-naphthyridine (cas: 204452-91-5) belongs to naphthyridine derivatives. Six naphthyridine isomers exist, based on the positions of the nitrogen atoms; they can be in the 1,5, 1,6, 1,7, 1,8, 2,6, or 2,7 positions. Enoxacin, nalidixic acid, and trovafloxacin are 1,8-naphthyridine derivatives with antibacterial properties related to the fluoroquinolones.Name: 7-(Dimethoxymethyl)-1,2,3,4-tetrahydro-1,8-naphthyridine

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

Estimation of electron affinity based on structure activity relationships was written by Hilal, S. H.;Carreira, L. A.;Karickhoff, S. W.;Melton, C. M.. And the article was included in Quantitative Structure-Activity Relationships in 1993.Electric Literature of C8H6N2 This article mentions the following:

Electron affinity for a wide range of organic mols. was calculated from mol. structure using the chem. reactivity models developed in SPARC. These models are based on fundamental chem. structure theory applied to the prediction of chem. reactivities for organic mols. strictly from mol. structure. The energy differences between the LUMO state and the HOMO state for a mol. of interest are factored into mechanistic components including the field, sigma induction and resonance contributions to these energy differences. The RMS deviation between observed and calculated electron affinities was found to be less than 0.14 e.v. for a large set of organic mols. In the experiment, the researchers used many compounds, for example, 2,6-Naphthyridine (cas: 253-50-9Electric Literature of C8H6N2).

2,6-Naphthyridine (cas: 253-50-9) belongs to naphthyridine derivatives. The naphthyridine ring system, being very π-deficient, is highly vulnerable towards nucleophilic attack, and consequently there has been extensive investigation of reactions involving nitrogen nucleophiles. 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.Electric Literature of C8H6N2

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

Simultaneous determination of 72 veterinary drugs in shrimp by modified QuEChERS and high performance liquid chromatography-tandem mass spectrometry was written by Bu, Ming-nan;Shi, Zhi-hong;Kang, Jian;Fan, Chun-lin;Pang, Guo-fang. And the article was included in Fenxi Ceshi Xuebao in 2012.Application In Synthesis of 1-Ethyl-6-fluoro-4-oxo-7-(piperazin-1-yl)-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid sesquihydrate This article mentions the following:

A method was developed for the simultaneous determination of 72 veterinary residues in shrimps by QuEChERS and high performance liquid chromatog.-tandem mass spectrometry. The sample was extracted with 5% acetic acid-acetonitrile, and the supernatant liquid was directly purified with C₁₈, meanwhile, acetonitrile was used for the precipitation of protein. The extract was evaporated under nitrogen stream, and redissolved with 1 mL 0.1% formic acid-acetonitrile(4:1). Prior to the injection into LC-MS/MS, the sample was filtered through a 0.22μm filter membrane. The HPLC separation was performed on ZORBAX SB-C₁₈ column by gradient elution with acetonitrile and 0.1%formic acid as mobile phase. The anal. of target compounds was carried out with electrospray ionization(ESI) under multi-reaction monitoring(MRM) mode. The external standard method was used for quantification. Under the optimal conditions, the correlation coefficients for 97.2% of the veterinaries were larger than 0.95 in the linear range of 0.1-1840μg/kg, and the limits of quantitation ranged from 0.02μg/kg to 33.58μg/kg. The recoveries of 72 veterinary at three spiked levels were between 61% and 119%, except that for di-Bu succinate, cefapirin, cefquinome, ceftiofur, lincomycin ane diazinon were between 38% and 58%, and their relative standard deviations were in the range of 1.6%-20%. The established method was used for the screening and determination of real samples(pteris shrimp, freshwater shrimp and sea shrimp) bought from supermarket. It was shown that no residue was detected in the sea shrimp and pteris shrimp samples, and 4.0μg/kg of sulfadiazine as well as 2.2μg/kg of sulfamethoxazole were found in freshwater shrimp sample, but the concentrations were all lower than the MRLs. In the experiment, the researchers used many compounds, for example, 1-Ethyl-6-fluoro-4-oxo-7-(piperazin-1-yl)-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid sesquihydrate (cas: 84294-96-2Application In Synthesis of 1-Ethyl-6-fluoro-4-oxo-7-(piperazin-1-yl)-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid sesquihydrate).

1-Ethyl-6-fluoro-4-oxo-7-(piperazin-1-yl)-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid sesquihydrate (cas: 84294-96-2) 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. 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.Application In Synthesis of 1-Ethyl-6-fluoro-4-oxo-7-(piperazin-1-yl)-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid sesquihydrate

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

Protective effect of vinpocetine against neurotoxicity of manganese in adult male rats was written by Nadeem, Rania I.;Ahmed, Hebatalla I.;El-Sayeh, Bahia M.. And the article was included in Naunyn-Schmiedeberg’s Archives of Pharmacology in 2018.Synthetic Route of C22H26N2O2 This article mentions the following:

Vinpocetine, a synthetic derivative of the alkaloid vincamine, is used to improve the cognitive function in cerebrovascular diseases. The present work was designed to explore the potential neuroprotective mechanisms exerted by vinpocetine in the Mn-induced neurotoxicity in rats. Rats were allocated into four groups. First group was given saline. The other three groups were given MnCl₂; two of them were treated with either L-dopa, the gold standard antiparkinsonian drug, or vinpocetine. Rats receiving MnCl₂ exhibited lengthened catalepsy duration in the grid and bar tests, motor impairment in the open-field test and short-term memory deficit in the Y-maze test. Addnl., histol. examination revealed structural alterations and degeneration in different brain regions. Besides, striatal monoamines and mitochondrial complex I contents were declined, apoptotic biomarker caspase-3 expression and acetylcholinesterase activity were elevated. Moreover, oxidative stress and inflammation were detected in the striata. L-dopa or vinpocetine exerted protective effects against MnCl₂-induced neurotoxicity. It could be hypothesized that modulation of monoamines, upregulation of mitochondrial complex I, antioxidant, antiinflammatory, and antiapoptotic activities are significant mechanisms underlying the neuroprotective effect of vinpocetine in the Mn-induced neurotoxicity model in rats. In the experiment, the researchers used many compounds, for example, (41S,13aS)-Ethyl 13a-ethyl-2,3,41,5,6,13a-hexahydro-1H-indolo[3,2,1-de]pyrido[3,2,1-ij][1,5]naphthyridine-12-carboxylate (cas: 42971-09-5Synthetic Route of C22H26N2O2).

(41S,13aS)-Ethyl 13a-ethyl-2,3,41,5,6,13a-hexahydro-1H-indolo[3,2,1-de]pyrido[3,2,1-ij][1,5]naphthyridine-12-carboxylate (cas: 42971-09-5) 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. 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.Synthetic Route of C22H26N2O2

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

Some properties of semiempirical Hamiltonians was written by Koutecky, Jaroslav. And the article was included in Journal of Chemical Physics in 1967.Application of 253-50-9 This article mentions the following:

The Hamiltonian used in semiempirical Pariser-Parr-Pople (P.P.P)-type treatments is put in a form such that (a) the parameters on which correlation effects depend become obvious and (b) the part of the Hamiltonian responsible for deviations from pairing properties of conjugated heterocycles with alternant topology is isolated. A set of approx. rules based on this analysis is derived. The rules concerning the extent of correlation effects are compared for some conjugated hydrocarbons with computations by full configuration interaction in the π-electron approximation Generalizations are derived of known conditions under which heterocyclic systems are paired. The character of the two first excited states of heteroanalogs and heteroderivs. of alternant hydrocarbons is discussed, and rules determining deviations from the behavior of parent alternant hydrocarbons are formulated. This makes it possible to predict the polarizations of the first two transitions in these compounds in the P.P.P. approximation with limited configuration interaction. The predictions are compared with some results of calculations on azines and amines. In the experiment, the researchers used many compounds, for example, 2,6-Naphthyridine (cas: 253-50-9Application of 253-50-9).

2,6-Naphthyridine (cas: 253-50-9) belongs to naphthyridine derivatives. Six naphthyridine isomers are white solids with a surprisingly wide span of melting points: 1,6-Naphthyridine’s is the lowest at <40 ºC; 2,6-naphthyridine’s is the highest at 114–115 ºC. Enoxacin, nalidixic acid, and trovafloxacin are 1,8-naphthyridine derivatives with antibacterial properties related to the fluoroquinolones.Application of 253-50-9

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