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